Nutraceutical delivery systems: resveratrol encapsulation in grape seed oil nanoemulsions formed by spontaneous emulsification.

PubMed

Davidov-Pardo, Gabriel; McClements, David Julian

2015-01-15

The aim of this work was to fabricate nanoemulsions-based delivery systems to encapsulate resveratrol. Nanoemulsions were formed using spontaneous emulsification method: 10% oil phase (grape seed oil plus orange oil) and 10% surfactant (Tween 80) were titrated into 80% aqueous phase. An optimum orange oil-to-grape seed oil ratio of 1:1(w/w) formed small droplets (d ≈ 100 nm) with good stability to droplet growth. The maximum amount of resveratrol that could be dissolved in the oil phase was 120 ± 10 μg/ml. The effect of droplet size on the chemical stability of encapsulated resveratrol was examined by preparing systems with different mean droplet diameters of 220 ± 2; 99 ± 3; and 45 ± 0.4 nm. Encapsulation of resveratrol improved its chemical stability after exposure to UV-light: 88% retention in nanoemulsions compared to 50% in dimethylsulphoxide (DMSO). This study showed that resveratrol could be encapsulated within low-energy nanoemulsion-based delivery systems and protected against degradation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plant-made vaccine antigens and biopharmaceuticals

PubMed Central

Daniell, Henry; Singh, Nameirakpam D.; Mason, Hugh; Streatfield, Stephen J.

2009-01-01

Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large scale production, purification, functional characterization, oral delivery and preclinical evaluation. PMID:19836291

Biodegradable polymers for targeted delivery of anti-cancer drugs.

PubMed

Doppalapudi, Sindhu; Jain, Anjali; Domb, Abraham J; Khan, Wahid

2016-06-01

Biodegradable polymers have been used for more than three decades in cancer treatment and have received increased interest in recent years. A range of biodegradable polymeric drug delivery systems designed for localized and systemic administration of therapeutic agents as well as tumor-targeting macromolecules has entered into the clinical phase of development, indicating the significance of biodegradable polymers in cancer therapy. This review elaborates upon applications of biodegradable polymers in the delivery and targeting of anti-cancer agents. Design of various drug delivery systems based on biodegradable polymers has been described. Moreover, the indication of polymers in the targeted delivery of chemotherapeutic drugs via passive, active targeting, and localized drug delivery are also covered. Biodegradable polymer-based drug delivery systems have the potential to deliver the payload to the target and can enhance drug availability at desired sites. Systemic toxicity and serious side effects observed with conventional cancer therapeutics can be significantly reduced with targeted polymeric systems. Still, there are many challenges that need to be met with respect to the degradation kinetics of the system, diffusion of drug payload within solid tumors, targeting tumoral tissue and tumor heterogeneity.

WE-DE-BRA-11: A Study of Motion Tracking Accuracy of Robotic Radiosurgery Using a Novel CCD Camera Based End-To-End Test System

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

Wang, L; M Yang, Y; Nelson, B

Purpose: A novel end-to-end test system using a CCD camera and a scintillator based phantom (XRV-124, Logos Systems Int’l) capable of measuring the beam-by-beam delivery accuracy of Robotic Radiosurgery (CyberKnife) was developed and reported in our previous work. This work investigates its application in assessing the motion tracking (Synchrony) accuracy for CyberKnife. Methods: A QA plan with Anterior and Lateral beams (with 4 different collimator sizes) was created (Multiplan v5.3) for the XRV-124 phantom. The phantom was placed on a motion platform (superior and inferior movement), and the plans were delivered on the CyberKnife M6 system using four motion patterns:more » static, Sine- wave, Sine with 15° phase shift, and a patient breathing pattern composed of 2cm maximum motion with 4 second breathing cycle. Under integral recording mode, the time-averaged beam vectors (X, Y, Z) were measured by the phantom and compared with static delivery. In dynamic recording mode, the beam spots were recorded at a rate of 10 frames/second. The beam vector deviation from average position was evaluated against the various breathing patterns. Results: The average beam position of the six deliveries with no motion and three deliveries with Synchrony tracking on ideal motion (sinewave without phase shift) all agree within −0.03±0.00 mm, 0.10±0.04, and 0.04±0.03 in the X, Y, and X directions. Radiation beam width (FWHM) variations are within ±0.03 mm. Dynamic video record showed submillimeter tracking stability for both regular and irregular breathing pattern; however the tracking error up to 3.5 mm was observed when a 15 degree phase shift was introduced. Conclusion: The XRV-124 system is able to provide 3D and 4D targeting accuracy for CyberKnife delivery with Synchrony. The experimental results showed sub-millimeter delivery in phantom with excellent correlation in target to breathing motion. The accuracy was degraded when irregular motion and phase shift was introduced.« less

Micro/nanoparticle adjuvants for antileishmanial vaccines: present and future trends.

PubMed

Badiee, Ali; Heravi Shargh, Vahid; Khamesipour, Ali; Jaafari, Mahmoud Reza

2013-01-21

Leishmania infection continues to have a major impact on public health inducing significant morbidity and mortality mostly in the poorest populations. Drug resistance, toxicity and side effects associated with expensive chemotherapeutic treatments and difficult reservoir control emphasize the need for a safe and effective vaccine which is not available yet. Although, Leishmanization (LZ) was shown to be effective against cutaneous leishmaniasis, standardization and safety are the main problems of LZ. First generation killed parasites demonstrated limited efficacy in phase 3 trials and moreover well defined molecules have not reached to phase 3 yet. Limited efficacy in vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Hence, the use of particulate delivery systems as carriers for antigen and/or immunostimulatory adjuvants for effective delivery to the antigen-presenting cells (APCs) is a valuable strategy to enhance vaccine efficacies. Particle-based delivery systems such as emulsions, liposomes, virosomes, and polymeric microspheres have the potential for successfully delivering antigens, which can then be further improved via incorporation of additional antigenic or immustimulatory adjuvant components in or onto the particle carrier system. In this review, we have attempted to provide a list of particulate vaccine delivery systems involved in the production of candidate leishmaniasis vaccines and introduced some potentially useful vaccine delivery systems for leishmaniasis in future experiments. In conclusion, combination vaccines (adjuvant systems) composed of candidate antigens and more importantly well-developed particulate delivery systems, such as lipid-based particles containing immunostimulatory adjuvants, have a chance to succeed as antileishmanial vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Extinguishing agent for magnesium fire, phases 5 and 6

NASA Astrophysics Data System (ADS)

Beeson, H. D.; Tapscott, R. E.; Mason, B. E.

1987-07-01

This report documents the validation testing of the extinguishing system for metal fires developed as part of Phases 1 to 4. The results of this validation testing form the basis of information from which draft military specifications necessary to procure the agent and the agent delivery system may be developed. The developed system was tested against a variety of large-scale metal fire scenarios and the capabilities of the system were assessed. In addition the response of the system to storage and to changes in ambient conditions was tested. Results of this testing revealed that the developed system represented a reliable metal fire extinguishing system that could control and extinguish very large metal fires. The specifications developed for the agent and for the delivery system are discussed in detail.

Preparation and the in vitro evaluation of nanoemulsion system for the transdermal delivery of granisetron hydrochloride.

PubMed

Zheng, Wen-wu; Zhao, Ling; Wei, Yu-meng; Ye, Yun; Xiao, Shun-han

2010-08-01

The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.

Phase Change Permeation Technology For Environmental Control Life Support Systems

NASA Technical Reports Server (NTRS)

Wheeler, Raymond M.

2014-01-01

Use of a phase change permeation membrane (Dutyion [Trademark]) to passively and selectively mobilize water in microgravity to enable improved water recovery from urine/brine for Environment Control and Life Support Systems (ECLSS) and water delivery to plans for potential use in microgravity.

Progress update on cryogenic system for ARIEL E-linac at TRIUMF

NASA Astrophysics Data System (ADS)

Koveshnikov, A.; Bylinskii, I.; Hodgson, G.; Yosifov, D.

2014-01-01

TRIUMF is involved in a major upgrade. The Advanced Rare IsotopeE Laboratory (ARIEL) has become a fully funded project in July 2010. A 10 mA 50 MeV SRF electron linac (e-linac) operating CW at 1.3 GHz is the key component of this initiative. This machine will serve as a second independent photo-fission driver for Rare Isotope Beams (RIB) production at TRIUMF's Isotope Separator and Accelerator (ISAC) facility. The cryogens delivery system requirements are driven by the electron accelerator cryomodule design [1, 2]. Since commencement of the project in 2010 the cryogenic system of e-linac has moved from the conceptual design phase into engineering design and procurement stage. The present document summarizes the progress in cryogenic system development and construction. Current status of e-linac cryogenic system including details of LN2 storage and delivery systems, and helium subatmospheric (SA) system is presented. The first phase of e-linac consisting of two cryomodules, cryogens storage, delivery, and distribution systems, and a 600 W class liquid helium cryoplant is scheduled for installation and commissioning by year 2014.

Food emulsions as delivery systems for flavor compounds: A review.

PubMed

Mao, Like; Roos, Yrjö H; Biliaderis, Costas G; Miao, Song

2017-10-13

Food flavor is an important attribute of quality food, and it largely determines consumer food preference. Many food products exist as emulsions or experience emulsification during processing, and therefore, a good understanding of flavor release from emulsions is essential to design food with desirable flavor characteristics. Emulsions are biphasic systems, where flavor compounds are partitioning into different phases, and the releases can be modulated through different ways. Emulsion ingredients, such as oils, emulsifiers, thickening agents, can interact with flavor compounds, thus modifying the thermodynamic behavior of flavor compounds. Emulsion structures, including droplet size and size distribution, viscosity, interface thickness, etc., can influence flavor component partition and their diffusion in the emulsions, resulting in different release kinetics. When emulsions are consumed in the mouth, both emulsion ingredients and structures undergo significant changes, resulting in different flavor perception. Special design of emulsion structures in the water phase, oil phase, and interface provides emulsions with great potential as delivery systems to control flavor release in wider applications. This review provides an overview of the current understanding of flavor release from emulsions, and how emulsions can behave as delivery systems for flavor compounds to better design novel food products with enhanced sensorial and nutritional attributes.

Introducing vouchers for malaria prevention in Ghana and Tanzania: context and adoption of innovation in health systems.

PubMed

de Savigny, Don; Webster, Jayne; Agyepong, Irene Akua; Mwita, Alex; Bart-Plange, Constance; Baffoe-Wilmot, Aba; Koenker, Hannah; Kramer, Karen; Brown, Nick; Lengeler, Christian

2012-10-01

There are striking similarities in health system and other contexts between Tanzania and Ghana that are relevant to the scaling up of continuous delivery of insecticide treated nets (ITNs) for malaria prevention. However, specific contextual factors of relevance to ITN delivery have led implementation down very different pathways in the two countries. Both countries have made major efforts and investments to address this intervention through integrating consumer discount vouchers into the health system. Discount vouchers require arrangements among the public, private and non-governmental sectors and constitute a complex intervention in both health systems and business systems. In Tanzania, vouchers have moved beyond the planning agenda, had policies and programmes formulated, been sustained in implementation at national scale for many years and have become as of 2012 the main and only publicly supported continuous delivery system for ITNs. In Ghana national-scale implementation of vouchers never progressed beyond consideration on the agenda and piloting towards formulation of policy; and the approach was replaced by mass distribution campaigns with less dependency on or integration with the health system. By 2011, Ghana entered a phase with no publicly supported continuous delivery system for ITNs. To understand the different outcomes, we compared the voucher programme timelines, phases, processes and contexts in both countries in reference to the main health system building blocks (governance, human resources, financing, informatics, technologies and service delivery). Contextual factors which provided an enabling environment for the voucher scheme in Tanzania did not do so in Ghana. The voucher scheme was never seen as an appropriate national strategy, other delivery systems were not complementary and the private sector was under-developed. The extensive time devoted to engagement and consensus building among all stakeholders in Tanzania was an important and clearly enabling difference, as was public sector support of the private sector. This contributed to the alignment of partner action behind a single co-ordinated strategy at service delivery level which in turn gave confidence to the business sector and avoided the 'interference' of competing delivery systems that occurred in Ghana. Principles of systems thinking for intervention design correctly emphasize the importance of enabling contexts and stakeholder management.

Waste Feed Delivery System Phase 1 Preliminary Reliability and Availability and Maintainability Analysis [SEC 1 and 2

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

CARLSON, A.B.

The document presents updated results of the preliminary reliability, availability, maintainability analysis performed for delivery of waste feed from tanks 241-AZ-101 and 241-AN-105 to British Nuclear Fuels Limited, inc. under the Tank Waste Remediation System Privatization Contract. The operational schedule delay risk is estimated and contributing factors are discussed.

Expert system verification and validation study. Phase 2: Requirements Identification. Delivery 2: Current requirements applicability

NASA Technical Reports Server (NTRS)

1991-01-01

The second phase of a task is described which has the ultimate purpose of ensuring that adequate Expert Systems (ESs) Verification and Validation (V and V) tools and techniques are available for Space Station Freedom Program Knowledge Based Systems development. The purpose of this phase is to recommend modifications to current software V and V requirements which will extend the applicability of the requirements to NASA ESs.

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading.

PubMed

Streck, Letícia; Sarmento, Víctor H V; Machado, Paula R L; Farias, Kleber J S; Fernandes-Pedrosa, Matheus F; da Silva-Júnior, Arnóbio Antônio

2016-06-30

Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

PubMed Central

Streck, Letícia; Sarmento, Víctor H. V.; Machado, Paula R. L.; Farias, Kleber J. S.; Fernandes-Pedrosa, Matheus F.; da Silva-Júnior, Arnóbio Antônio

2016-01-01

Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment. PMID:27376278

Space-Based Solar Power Conversion and Delivery Systems Study. Volume 1: Executive Summary

NASA Technical Reports Server (NTRS)

1977-01-01

The research concerning space-based solar power conversion and delivery systems is summarized. The potential concepts for a photovoltaic satellite solar power system was studied with emphasis on ground output power levels of 5,000 MW and 10,000 MW. A power relay satellite, and certain aspects of the economics of these systems were also studied. A second study phase examined in greater depth the technical and economic aspects of satellite solar power systems. Throughout this study, the focus was on the economics of satellite solar power. The results indicate technical feasibility of the concept, and provide a preliminary economic justification for the first phase of a substantial development program. A development program containing test satellites is recommended. Also, development of alternative solar cell materials (other than silicon) is recommended.

TIL system with nonlinear phase conjugation

NASA Astrophysics Data System (ADS)

Khizhnyak, Anatoliy; Markov, Vladimir

2007-09-01

Efficient laser beam delivery on a distant target remains a key problem for practical implementation of tactical laser systems. Since the conventional target-in-the-loop (TIL) concept is generally not effective in such operational environments, new solutions are needed. In this report we discuss an innovative approach for effective compensation of laser beam aberrations in TIL systems. It is based on a recently devised technique that combines optical phase conjugation (OPC) with a TIL system for effective hot-spot formation. The proposed method should enable delivery of enhanced density laser energy to a target within a finite number of iteration cycles. Using the model based on an analogy between the TIL system and laser resonator, pointing of the laser beam on the target is performed at the image plane, resulting in reduced hot-spot formation time.

Extinguishing Agent for Magnesium Fire: Phases 5 and 6.

DTIC Science & Technology

1987-07-01

This report documents the validation testing of the extinguishing system for metal fires developed as part of Phases I-IV. The results of this...system represented a reliable metal fire extinguishing system that could control and extinguish very large metal fires . The specifications developed for...the agent and for the delivery system are discussed in detail. Keywords: Fire suppression, Metal fires , Fire extinguishers.

Lecithin based lamellar liquid crystals as a physiologically acceptable dermal delivery system for ascorbyl palmitate.

PubMed

Gosenca, Mirjam; Bešter-Rogač, Marija; Gašperlin, Mirjana

2013-09-27

Liquid crystalline systems with a lamellar structure have been extensively studied as dermal delivery systems. Ascorbyl palmitate (AP) is one of the most studied and used ascorbic acid derivatives and is employed as an antioxidant to prevent skin aging. The aim of this study was to develop and characterize skin-compliant dermal delivery systems with a liquid crystalline structure for AP. First, a pseudoternary phase diagram was constructed using Tween 80/lecithin/isopropyl myristate/water at a Tween 80/lecithin mass ratio of 1/1, and the region of lamellar liquid crystals was identified. Second, selected unloaded and AP-loaded lamellar liquid crystal systems were physicochemically characterized with polarizing optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology techniques. The interlayer spacing and rheological parameters differ regarding quantitative composition, whereas the microstructure of the lamellar phase was affected by the AP incorporation, resulting either in additional micellar structures (at 25 and 32 °C) or being completely destroyed at higher temperature (37°C). After this, the study was oriented towards in vitro cytotoxicity evaluation of lamellar liquid crystal systems on a keratinocyte cell line. The results suggest that the lamellar liquid crystals that were developed could be used as a physiologically acceptable dermal delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Retinal Drug Delivery System, Phase I

DTIC Science & Technology

1997-06-01

retinal lesions, need an antibiotic, an anti-inflammatory agent, and an analgesic, and, recent research suggests that it might be advantageous to treat...predetermined) manner, that is, control over time, amount and sequence, either continuously or pulsed. This system would have all of the advantages of...delivery would produce the same therapeutic benefits while reducing side effects and toxic exposure. Recent studies have shown the advantages of pulse

Biophysics and Thermodynamics: The Scientific Building Blocks of Bio-inspired Drug Delivery Nano Systems.

PubMed

Demetzos, Costas

2015-06-01

Biophysics and thermodynamics are considered as the scientific milestones for investigating the properties of materials. The relationship between the changes of temperature with the biophysical variables of biomaterials is important in the process of the development of drug delivery systems. Biophysics is a challenge sector of physics and should be used complementary with the biochemistry in order to discover new and promising technological platforms (i.e., drug delivery systems) and to disclose the 'silence functionality' of bio-inspired biological and artificial membranes. Thermal analysis and biophysical approaches in pharmaceuticals present reliable and versatile tools for their characterization and for the successful development of pharmaceutical products. The metastable phases of self-assembled nanostructures such as liposomes should be taken into consideration because they represent the thermal events can affect the functionality of advanced drug delivery nano systems. In conclusion, biophysics and thermodynamics are characterized as the building blocks for design and development of bio-inspired drug delivery systems.

SU-E-T-151: Breathing Synchronized Delivery (BSD) Planning for RapicArc Treatment

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

Lu, W; Chen, M; Jiang, S

2015-06-15

Purpose: To propose a workflow for breathing synchronized delivery (BSD) planning for RapicArc treatment. Methods: The workflow includes three stages: screening/simulation, planning, and delivery. In the screening/simulation stage, a 4D CT with the corresponding breathing pattern is acquired for each of the selected patients, who are able to follow their own breathing pattern. In the planning stage, one breathing phase is chosen as the reference, and contours are delineated on the reference image. Deformation maps to other phases are performed along with contour propagation. Based on the control points of the initial 3D plan for the reference phase and themore » respiration trace, the correlation with respiration phases, the leaf sequence and gantry angles is determined. The beamlet matrices are calculated with the corresponding breathing phase and deformed to the reference phase. Using the 4D dose evaluation tool and the original 3D plan DVHs criteria, the leaf sequence is further optimized to meet the planning objectives and the machine constraints. In the delivery stage, the patients are instructed to follow the programmed breathing patterns of their own, and all other parts are the same as the conventional Rapid-Arc delivery. Results: Our plan analysis is based on comparison of the 3D plan with a static target (SD), 3D plan with motion delivery (MD), and the BSD plan. Cyclic motion of range 0 cm to 3 cm was simulated for phantoms and lung CT. The gain of the BSD plan over MD is significant and concordant for both simulation and lung 4DCT, indicating the benefits of 4D planning. Conclusion: Our study shows that the BSD plan can approach the SD plan quality. However, such BSD scheme relies on the patient being able to follow the same breathing curve that is used in the planning stage during radiation delivery. Funded by Varian Medical Systems.« less

Recent advances in oral pulsatile drug delivery.

PubMed

Kalantzi, Lida E; Karavas, Evangelos; Koutris, Efthimios X; Bikiaris, Dimitrios N

2009-01-01

Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

A reversed-phase high-performance liquid chromatography method for bovine serum albumin assay in pharmaceutical dosage forms and protein/antigen delivery systems.

PubMed

Hamidi, Mehrdad; Zarei, Najmeh

2009-05-01

Bovine serum albumin (BSA) is among the most widely used proteins in protein formulations as well as in the development of novel delivery systems as a typical model for therapeutic/diagnostic proteins and the new versions of vaccines. The development of reliable and easily available assay methods for quantitation of this protein would therefore play a crucial role in these types of studies. A simple gradient reversed-phase high-performance liquid chromatography with ultra-violet detection (HPLC-UV) method has been developed for quantitation of BSA in dosage forms and protein delivery systems. The method produced linear responses throughout the wide BSA concentration range of 1 to 100 micro g/mL. The average within-run and between-run variations of the method within the linear concentration range of BSA were 2.46% and 2.20%, respectively, with accuracies of 104.49% and 104.58% for within-run and between-run samples, respectively. The limits of detection (LOD) and quantitation (LOQ) of the method were 0.5 and 1 microg/mL, respectively. The method showed acceptable system suitability indices, which enabled us to use it successfully during our particulate vaccine delivery research project. Copyright 2009 John Wiley & Sons, Ltd.

Encapsulation of Polymethoxyflavones in Citrus Oil Emulsion-Based Delivery Systems.

PubMed

Yang, Ying; Zhao, Chengying; Chen, Jingjing; Tian, Guifang; McClements, David Julian; Xiao, Hang; Zheng, Jinkai

2017-03-01

The purpose of this work was to elucidate the effects of citrus oil type on polymethoxyflavone (PMF) solubility and on the physicochemical properties of PMF-loaded emulsion-based delivery systems. Citrus oils were extracted from mandarin, orange, sweet orange, and bergamot. The major constituents were determined by GC/MS: sweet orange oil (97.4% d-limonene); mandarin oil (72.4% d-limonene); orange oil (67.2% d-limonene); and bergamot oil (34.6% linalyl acetate and 25.3% d-limonene). PMF-loaded emulsions were fabricated using 10% oil phase (containing 0.1% w/v nobiletin or tangeretin) and 90% aqueous phase (containing 1% w/v Tween 80) using high-pressure homogenization. Delivery systems prepared using mandarin oil had the largest mean droplet diameters (386 or 400 nm), followed by orange oil (338 or 390 nm), bergamot oil (129 or 133 nm), and sweet orange oil (122 or 126 nm) for nobiletin- or tangeretin-loaded emulsions, respectively. The optical clarity of the emulsions increased with decreasing droplet size due to reduced light scattering. The viscosities of the emulsions (with or without PMFs) were similar (1.3 to 1.4 mPa·s), despite appreciable differences in oil phase viscosity. The loading capacity and encapsulation efficiency of the emulsions depended on carrier oil type, with bergamot oil giving the highest loading capacity. In summary, differences in the composition and physical characteristics of citrus oils led to PMF-loaded emulsions with different encapsulation and physicochemical characteristics. These results will facilitate the rational design of emulsion-based delivery systems for encapsulation of PMFs and other nutraceuticals in functional foods and beverages.

Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan.

PubMed

Bruce, Jeffrey N; Fine, Robert L; Canoll, Peter; Yun, Jonathan; Kennedy, Benjamin C; Rosenfeld, Steven S; Sands, Stephen A; Surapaneni, Krishna; Lai, Rose; Yanes, Candix L; Bagiella, Emilia; DeLaPaz, Robert L

2011-12-01

Convection-enhanced delivery of chemotherapeutics for the treatment of malignant glioma is a technique that delivers drugs directly into a tumor and the surrounding interstitium through continuous, low-grade positive-pressure infusion. This allows high local concentrations of drug while overcoming the limitations imposed by toxicity and the blood-brain barrier in systemic therapies that prevent the use of many potentially effective drugs. To examine the safety profile of a conventional chemotherapeutic agent, topotecan, via convection-enhanced delivery in the treatment of recurrent malignant gliomas and secondarily to assess radiographic response and survival. We performed a prospective, dose-escalation phase Ib study of the topoisomerase-I inhibitor topotecan given by convection-enhanced delivery in patients with recurrent malignant gliomas. Significant antitumor activity as described by radiographic changes and prolonged overall survival with minimal drug-associated toxicity was demonstrated. A maximum tolerated dose was established for future phase II studies. Topotecan by convection-enhanced delivery has significant antitumor activity at concentrations that are nontoxic to normal brain. The potential for use of this therapy as a generally effective treatment option for malignant gliomas will be tested in subsequent phase II and III trials.

Design, Construction, Demonstration and Delivery of an Automated Narrow Gap Welding System.

DTIC Science & Technology

1983-03-31

evaluated on the Narrow Gap welding system. By using the combinational qas shielding assembly, it is now possible to reduce the gas flow rates to a value...AD-A145 496 DESIGN CONSTRUCTION DEMONSTRATION AND DE IVER OF AN AUTOMATED NARROW GAP WELDING SYSTEM(U) CRC AUTOMATIC WELDING CO HODSTON SX 31 MAR 83...STANDARDS-963 - A CRC REPORT NO. NAV A/W 7 0PHASE 3 REPORT ON SDESIGN, CONSTRUCTION, DEMONSTRATION AND DELIVERY OF AN AUTOMATED NARROW GAP WELDING

California Integrated Service Delivery Evaluation Report. Phase I

ERIC Educational Resources Information Center

Moore, Richard W.; Rossy, Gerard; Roberts, William; Chapman, Kenneth; Sanchez, Urte; Hanley, Chris

2010-01-01

This study is a formative evaluation of the OneStop Career Center Integrated Service Delivery (ISD) Model within the California Workforce System. The study was sponsored by the California Workforce Investment Board. The study completed four in-depth case studies of California OneStops to describe how they implemented the ISD model which brings…

Characterization of the Dynamic Pressure Response of Fuels in Microchannels

NASA Astrophysics Data System (ADS)

Haendler, Brenda; Pisano, Albert; Liepmann, Dorian

2004-11-01

In order to create a self-pumping fuel vaporization and delivery systems for a MEMS rotary engine power system, the dynamic pressure response due to phase eruption of fuels in micro channels must be characterized. Testing is done using micro channels with diameters the same order of magnitude as the critical bubble radius, a constant mass flow rate syringe pump, and a steady heat source. Pressure changes in the micro channel due to the periodic movement of the phase change meniscus are measured for a variety of flow conditions. A discrete Fourier transform is performed on the data to determine the dominant frequencies in the signal. Critical trends are discussed comparing both the frequency and the amplitude of the pressure spikes for a variety of temperatures and flow rates. The results presented on the trends in the pressure signature due to phase eruption for fuels are then related back to the fuel delivery system, which is using a nozzle-diffuser design to accomplish positive flow rectification given the periodic pressure condition at the phase eruption interface.

Novel Surface Modification Method for Ultrasupercritical Coal-Fired Boilers

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

Xiao, T. Danny

2013-05-22

US Department of Energy seeks an innovative coating technology for energy production to reduce the emission of SOx, NOx, and CO2 toxic gaseous species. To realize this need, Inframat Corporation (IMC) proposed an SPS thermal spray coating technique to produce ultrafine/nanocoatings that can be deposited onto the surfaces of high temperature boiler tubes, so that higher temperatures of boiler operation becomes possible, leading to significantly reduced emission of toxic gaseous species. It should be noted that the original PI was Dr. Xinqing Ma, who after 1.5 year conducting this project left Inframat in December, 2008. Thus, the PI was transferredmore » to Dr. Danny Xiao, who originally co-authored the proposal with Dr. Ma, in order to carry the project into a completion. Phase II Objectives: The proposed technology has the following attributes, including: (1). Dispersion of a nanoparticle or alloyed particle in a solvent to form a uniform slurry feedstock; (2). Feeding of the slurry feedstock into a thermal spray flame, followed by deposition of the slurry feedstock onto substrates to form tenacious nanocoatings; (3). High coating performance: including high bonding strength, and high temperature service life in the temperature range of 760oC/1400oF. Following the above premises, our past Phase I project has demonstrated the feasibility in small scale coatings on boiler substrates. The objective of this Phase II project was to focus on scale-up the already demonstrated Phase I work for the fabrication of SPS coatings that can satisfy DOE's emission reduction goals for energy production operations. Specifically, they are: (1). Solving engineering problems to scale-up the SPS-HVOF delivery system to a prototype production sub-delivery system; (2). Produce ultrafine/nanocoatings using the scale-up prototype system; (3). Demonstrate the coated components using the scale-up device having superior properties. Proposed Phase II Tasks: In the original Phase II proposal, we have six (6) technical tasks plus one (1) reporting task, as described below: Task 1 Scale-up and optimize the SPS process; Task 2 Coating design and fabrication with desired microstructure; Task 3 Evaluate microstructure and physical properties; Task 4 Test performance of long-term corrosion and erosion; Task 5 Test mechanical property and reliability; Task 6 Coating of a prototype boiler tube for evaluation; Task 7 Reporting task. To date, we have already completed all the technical tasks of 1 through 6. Major Phase II Achievements: In this four (4) year working period, Inframat had spent great effort to complete the proposed tasks. The project had been completed; the goals have been accomplished. Major achievements obtained include: (1). Developed a prototype scale-up slurry feedstock delivery system for thermal spray coatings; (2). Successfully coated high performance coatings using this scale-up slurry delivery system; (3). Commercial applications in energy efficiency and clean energy components have been developed using this newly fabricated slurry feedstock delivery system.« less

In situ-forming hydrogels for sustained ophthalmic drug delivery.

PubMed

Nanjawade, Basavaraj K; Manvi, F V; Manjappa, A S

2007-09-26

Ophthalmic drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. The conventional ocular drug delivery systems like solutions, suspensions, and ointments show drawbacks such as increased precorneal elimination, high variability in efficiency, and blurred vision respectively. In situ-forming hydrogels are liquid upon instillation and undergo phase transition in the ocular cul-de-sac to form visco-elastic gel and this provides a response to environmental changes. In the past few years, an impressive number of novel temperature, pH, and ion induced in situ-forming systems have been reported for sustain ophthalmic drug delivery. Each system has its own advantages and drawbacks. The choice of a particular hydrogel depends on its intrinsic properties and envisaged therapeutic use. This review includes various temperature, pH, and ion induced in situ-forming polymeric systems used to achieve prolonged contact time of drugs with the cornea and increase their bioavailability.

Critical review: Injectability of calcium phosphate pastes and cements.

PubMed

O'Neill, R; McCarthy, H O; Montufar, E B; Ginebra, M-P; Wilson, D I; Lennon, A; Dunne, N

2017-03-01

Calcium phosphate cements (CPC) have seen clinical success in many dental and orthopaedic applications in recent years. The properties of CPC essential for clinical success are reviewed in this article, which includes properties of the set cement (e.g. bioresorbability, biocompatibility, porosity and mechanical properties) and unset cement (e.g. setting time, cohesion, flow properties and ease of delivery to the surgical site). Emphasis is on the delivery of calcium phosphate (CaP) pastes and CPC, in particular the occurrence of separation of the liquid and solid components of the pastes and cements during injection; and established methods to reduce this phase separation. In addition a review of phase separation mechanisms observed during the extrusion of other biphasic paste systems and the theoretical models used to describe these mechanisms are discussed. Occurrence of phase separation of calcium phosphate pastes and cements during injection limits their full exploitation as a bone substitute in minimally invasive surgical applications. Due to lack of theoretical understanding of the phase separation mechanism(s), optimisation of an injectable CPC that satisfies clinical requirements has proven difficult. However, phase separation of pastes during delivery has been the focus across several research fields. Therefore in addition to a review of methods to reduce phase separation of CPC and the associated constraints, a review of phase separation mechanisms observed during extrusion of other pastes and the theoretical models used to describe these mechanisms is presented. It is anticipated this review will benefit future attempts to develop injectable calcium phosphate based systems. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Protein-Based Nanomedicine Platforms for Drug Delivery

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

Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong

2009-08-03

Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They aremore » ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein based drug delivery system.« less

In situ gelling polymers in ocular drug delivery systems: a review.

PubMed

Mundada, Atish S; Avari, Jasmine G

2009-01-01

The review article aims to highlight the recent developments in various in situ gel-forming polymeric systems that are used to achieve prolonged contact time of drugs with the cornea and increase their ocular bioavailability. These phase-change polymers, which trigger the drug release in response to external stimuli, are the most investigated in controlled drug delivery. The present review summarizes in detail these various polymers, which undergo sol-gel transition due to physical (temperature) or chemical (pH, ions) stimuli when instilled in the eye. As a whole, this article provides valuable insight into current trends in the field of in situ gel-forming ocular drug delivery systems.

A concise review on smart polymers for controlled drug release.

PubMed

Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali

2016-06-01

Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications.

Design and evaluation of self-nanoemulsifying pellets of repaglinide.

PubMed

Desai, N S; Nagarsenker, M S

2013-09-01

The aim of study was to develop self-nanoemulsifying pellets (SNEP) for oral delivery of poorly water soluble drug, repaglinide (RPG). Solubility of RPG in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). The surfactants and cosurfactants were screened for their ability to emulsify oily phase. Ternary phase diagrams were constructed to identify nanoemulsification area for the selected systems. SNEDDS formulations with globule size less than 100 nm were evaluated for in vivo anti-hyperglycemic activity in neonatal streptozotocin rat model. A significant reduction in glucose levels was produced by optimized SNEDDS formulation in comparison to the control group. The optimized SNEDDS formulations were pelletized via extrusion/spheronization technique using microcrystalline cellulose and lactose. SNEP were characterized by X-ray powder diffraction and scanning electron microscopy. X-ray diffraction study indicated loss of crystallinity of RPG in SNEP. The SNEP exhibited good flow properties, mechanical strength and formed nanoemulsion with globule size less than 200 nm. SNEP showed in vitro release of more than 80% RPG in 10 min which was significantly higher than RPG containing reference pellets. In conclusion, our studies illustrated that RPG, a poorly water soluble drug can be successfully formulated into SNEP which can serve as a promising system for the delivery of poorly water soluble drugs.

[Strategy and collaboration between medicinal chemists and pharmaceutical scientists for drug delivery systems].

PubMed

Mano, Takashi

2013-01-01

In order to successfully apply drug delivery systems (DDS) to new chemical entities (NCEs), collaboration between medicinal chemists and formulation scientists is critical for efficient drug discovery. Formulation scientists have to use 'language' that medicinal chemists understand to help promote mutual understanding, and medicinal chemists and formulation scientists have to set up strategies to use suitable DDS technologies at the discovery phase of the programmes to ensure successful transfer into the development phase. In this review, strategies of solubilisation formulation for oral delivery, inhalation delivery, nasal delivery and bioconjugation are all discussed. For example, for oral drug delivery, multiple initiatives can be proposed to improve the process to select an optimal delivery option for an NCE. From a technical perspective, formulation scientists have to explain the scope and limitations of formulations as some DDS technologies might be applicable only to limited chemical spaces. Other limitations could be the administered dose and, cost, time and resources for formulation development and manufacturing. Since DDS selection is best placed as part of lead-optimisation, formulation scientists need to be involved in discovery projects at lead selection and optimisation stages. The key to success in their collaboration is to facilitate communication between these two areas of expertise at both a strategic and scientific level. Also, it would be beneficial for medicinal chemists and formulation scientists to set common goals to improve the process of collaboration and build long term partnerships to improve DDS.

Factors influencing the purity of electronic grade phosphine delivered to MOCVD tools

NASA Astrophysics Data System (ADS)

Feng, Jun; Owens, Mitch; Raynor, Mark W.

2010-04-01

Increasing mobility of InP films with usage time of one PH 3 cylinder prompted an investigation into factors influencing the purity of delivered PH 3. The presence of hygroscopic H xPO y residues in a delivery system greatly increases the dry-down time compared to that of a clean system. Static delivery system tests show increasing H 2O concentration with time and twice the increase in PH 3 versus N 2 over 48 h indicating reaction of metal oxides in components with PH 3 to generate H 2O. Gas purity may also vary during cylinder usage. Depletion of a high-purity PH 3 cylinder shows consistently low gas phase H 2O levels before phase-break but increasing levels after phase-break, as the cylinder depressurizes. The results highlight the importance of using pure PH 3, employing rigorous cycle-purging procedures to prevent H xPO y contamination, switching out cylinders in good time and using purification technology to control H 2O.

IDC System Specification Document.

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

Clifford, David J.

2014-12-01

This document contains the system specifications derived to satisfy the system requirements found in the IDC System Requirements Document for the IDC Reengineering Phase 2 project. Revisions Version Date Author/Team Revision Description Authorized by V1.0 12/2014 IDC Reengineering Project Team Initial delivery M. Harris

Preparation and evaluation of injectable Rasagiline mesylate dual-controlled drug delivery system for the treatment of Parkinson's disease.

PubMed

Jiang, Ying; Zhang, Xuemei; Mu, Hongjie; Hua, Hongchen; Duan, Dongyu; Yan, Xiuju; Wang, Yiyun; Meng, Qingqing; Lu, Xiaoyan; Wang, Aiping; Liu, Wanhui; Li, Youxin; Sun, Kaoxiang

2018-11-01

A microsphere-gel in situ forming implant (MS-Gel ISFI) dual-controlled drug delivery system was applied to a high water-soluble small-molecule compound Rasagiline mesylate (RM) for effective treatment of Parkinson's disease. This injectable complex depot system combined an in situ phase transition gel with high drug-loading and encapsulation efficiency RM-MS prepared by a modified emulsion-phase separation method and optimized by Box-Behnken design. It was evaluated for in vitro drug release, in vivo pharmacokinetics, and in vivo pharmacodynamics. We found that the RM-MS-Gel ISFI system showed no initial burst release and had a long period of in vitro drug release (60 days). An in vivo pharmacokinetic study indicated a significant reduction (p < .01) in the initial high plasma drug concentration of the RM-MS-Gel ISFI system compared to that of the single RM-MS and RM-in situ gel systems after intramuscular injection to rats. A pharmacodynamic study demonstrated a significant reduction (p < .05) in 6-hydroxydopamine-induced contralateral rotation behavior and an effective improvement (p < .05) in dopamine levels in the striatum of the lesioned side after 28 days in animals treated with the RM-MS-Gel ISFI compared with that of animals treated with saline. MS-embedded in situ phase transition gel is superior for use as a biodegradable and injectable sustained drug delivery system with a low initial burst and long period of drug release for highly hydrophilic small molecule drugs.

Commissioning of an integrated platform for time-resolved treatment delivery in scanned ion beam therapy by means of optical motion monitoring.

PubMed

Fattori, G; Saito, N; Seregni, M; Kaderka, R; Pella, A; Constantinescu, A; Riboldi, M; Steidl, P; Cerveri, P; Bert, C; Durante, M; Baroni, G

2014-12-01

The integrated use of optical technologies for patient monitoring is addressed in the framework of time-resolved treatment delivery for scanned ion beam therapy. A software application has been designed to provide the therapy control system (TCS) with a continuous geometrical feedback by processing the external surrogates tridimensional data, detected in real-time via optical tracking. Conventional procedures for phase-based respiratory phase detection were implemented, as well as the interface to patient specific correlation models, in order to estimate internal tumor motion from surface markers. In this paper, particular attention is dedicated to the quantification of time delays resulting from system integration and its compensation by means of polynomial interpolation in the time domain. Dedicated tests to assess the separate delay contributions due to optical signal processing, digital data transfer to the TCS and passive beam energy modulation actuation have been performed. We report the system technological commissioning activities reporting dose distribution errors in a phantom study, where the treatment of a lung lesion was simulated, with both lateral and range beam position compensation. The zero-delay systems integration with a specific active scanning delivery machine was achieved by tuning the amount of time prediction applied to lateral (14.61 ± 0.98 ms) and depth (34.1 ± 6.29 ms) beam position correction signals, featuring sub-millimeter accuracy in forward estimation. Direct optical target observation and motion phase (MPh) based tumor motion discretization strategies were tested, resulting in 20.3(2.3)% and 21.2(9.3)% median (IQR) percentual relative dose difference with respect to static irradiation, respectively. Results confirm the technical feasibility of the implemented strategy towards 4D treatment delivery, with negligible percentual dose deviations with respect to static irradiation.

Investigation of Fragment Antibody Stability and Its Release Mechanism from Poly(Lactide-co-Glycolide)-Triacetin Depots for Sustained-Release Applications.

PubMed

Chang, Debby P; Garripelli, Vivek Kumar; Rea, Jennifer; Kelley, Robert; Rajagopal, Karthikan

2015-10-01

Achieving long-term drug release from polymer-based delivery systems continues to be a challenge particularly for the delivery of large hydrophilic molecules such as therapeutic antibodies and proteins. Here, we report on the utility of an in situ-forming and injectable polymer-solvent system for the long-term release of a model antibody fragment (Fab1). The delivery system was prepared by dispersing a spray-dried powder of Fab1 within poly(lactide-co-glycolide) (PLGA)-triacetin solution. The formulation viscosity was within the range 1.0 ± 0.3 Pa s but it was injectable through a 27G needle. The release profile of Fab1, measured in phosphate-buffered saline (PBS), showed a lag phase followed by sustained-release phase for close to 80 days. Antibody degradation during its residence within the depot was comparable to its degradation upon long-term incubation in PBS. On the basis of temporal changes in surface morphology, stiffness, and depot mass, a mechanism to account for the drug release profile has been proposed. The unprecedented release profile and retention of greater than 80% of antigen-binding capacity even after several weeks demonstrates that PLGA-triacetin solution could be a promising system for the long-term delivery of biologics. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

PubMed

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

2015-12-07

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

Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

PubMed

Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

2016-02-10

Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

PubMed

Jug, Mario; Hafner, Anita; Lovrić, Jasmina; Kregar, Maja Lusina; Pepić, Ivan; Vanić, Željka; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena

2018-01-05

In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Smart sign enhancement, phase 2 : final report, September 2007.

DOT National Transportation Integrated Search

2007-09-01

An on line ordering system, called Smart Sign Ordering System (SSOS), was : developed by The University of Akron for Ohio Department of Transportation (ODOT) : in 2004. Driven by the demand of managing planning, fabrication, packaging and : delivery,...

NLC Special Projects

Science.gov Websites

Measurement (with NLC RF group) LCLS and related technologies (LCLS work related to NLC work) Collimation Systems (with Beam Delivery group) Combined Laser System (with NLC sources group) Polarized Positron Sources (with NLC sources group) Crab Cavity Phase Control System Timing and RF distribution System (with

Active phase compensation system for fiber optic holography

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Beheim, Glenn

1988-01-01

Fiber optic delivery systems promise to extend the application of holography to severe environments by simplifying test configurations and permitting the laser to be remotely placed in a more benign location. However, the introduction of optical fiber leads to phase stability problems. Environmental effects cause the pathlengths of the fibers to change randomly, preventing the formation of stationary interference patterns which are required for holography. An active phase control system has been designed and used with an all-fiber optical system to stabilize the phase difference between light emitted from two fibers, and to step the phase difference by 90 deg without applying any constraints on the placement of the fibers. The accuracy of the phase steps is shown to be better than 0.02 deg., and a stable phase difference can be maintained for 30 min. This system can be applied to both conventional and electro-optic holography, as well as to any system where the maintenance of an accurate phase difference between two coherent beams is required.

Active phase compensation system for fiber optic holography

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Beheim, Glenn

1989-01-01

Fiber optic delivery systems promise to extend the application of holography to severe environments by simplifying test configurations and permitting the laser to be remotely placed in a more benign location. However, the introduction of optical fiber leads to phase stability problems. Environmental effects cause the pathlengths of the fibers to change randomly, preventing the formation of stationary interference patterns which are required for holography. An active phase control system has been designed and used with an all-fiber optical system to stabilize the phase difference between light emitted from two fibers, and to step the phase difference by 90 deg without applying any constraints on the placement of the fibers. The accuracy of the phase steps is shown to be better than 0.02 deg., and a stable phase difference can be maintained for 30 min. This system can be applied to both conventional and electro-optic holography, as well as to any system where the maintenance of an accurate phase difference between two coherent beams is required.

The role of technology in reducing health care costs. Phase II and phase III.

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

Cilke, John F.; Parks, Raymond C.; Funkhouser, Donald Ray

2004-04-01

In Phase I of this project, reported in SAND97-1922, Sandia National Laboratories applied a systems approach to identifying innovative biomedical technologies with the potential to reduce U.S. health care delivery costs while maintaining care quality. The effort provided roadmaps for the development and integration of technology to meet perceived care delivery requirements and an economic analysis model for development of care pathway costs for two conditions: coronary artery disease (CAD) and benign prostatic hypertrophy (BPH). Phases II and III of this project, which are presented in this report, were directed at detailing the parameters of telemedicine that influence care deliverymore » costs and quality. These results were used to identify and field test the communication, interoperability, and security capabilities needed for cost-effective, secure, and reliable health care via telemedicine.« less

In Vivo Formation of Cubic Phase in Situ after Oral Administration of Cubic Phase Precursor Formulation Provides Long Duration Gastric Retention and Absorption for Poorly Water-Soluble Drugs.

PubMed

Pham, Anna C; Hong, Linda; Montagnat, Oliver; Nowell, Cameron J; Nguyen, Tri-Hung; Boyd, Ben J

2016-01-04

Lipid-based liquid crystalline systems based on the combination of digestible and nondigestible lipids have been proposed as potential sustained release delivery systems for oral delivery of poorly water-soluble drugs. The potential for cubic phase liquid crystal formation to induce dramatically extended gastric retention in vivo has been shown previously to strongly influence the resulting pharmacokinetics of incorporated drug. In vitro studies showing the in situ formation of cubic phase from a disordered precursor comprising a mixture of digestible and nondigestible lipids under enzymatic digestion have also recently been reported. Combining both concepts, here we show the potential for such systems to form in vivo, increasing gastric retention, and providing a sustained release effect for a model poorly water-soluble drug cinnarizine. A mixture of phytantriol and tributyrin at an 85:15 mass ratio, shown previously to form cubic phase under the influence of digestion, induced a similar pharmacokinetic profile to that in the absence of tributyrin, but completely different from tributyrin alone. The gastric retention of the formulation, assessed using micro-X-ray CT imaging, was also consistent with the pharmacokinetic behavior, where phytantriol alone and with 15% tributyrin was greater than that of tributyrin in the absence of phytantriol. Thus, the concept of precursor lipid systems that form cubic phase in situ during digestion in vivo has been demonstrated and opens new opportunities for sustained release of poorly water-soluble drugs.

Formulation and evaluation of lecithin organogel for topical delivery of fluconazole.

PubMed

Jadhav, Kisan R; Kadam, Vilasrao J; Pisal, Sambhaji S

2009-04-01

The purpose of the present study was to develop and investigate the suitability of microemulsion based lecithin organogel formulations for topical delivery of fluconazole in order to bypass its gastrointestinal adverse effects. The ternary phase diagrams were developed and various organogel formulations were prepared using pharmaceutically acceptable surfactant (lecithin) and ethyl oleate (EO). Solubility of fluconazole in EO and EO-lecithin reverse micellar system was determined. The transdermal permeability of fluconazole from different concentrations of lecithin organogels containing EO as oil phase was analyzed using Keshary-Chien diffusion cell through excised rat skin. Solubility of fluconazole in EO-lecithin reverse micellar system was almost 3 folds higher than that in EO. Gelation and immobilization of oil require critical solubility-insolubility balance of gelator. The occurrence of gel phase was lecithin concentration dependent and was observed in 10-60% w/v of system. Organogel containing 300 mM of lecithin showed the higher drug release and better relative consistency. Hence, it was selected for antifungal activity. The increase in antifungal activity of fluconazole in lecithin organogel may be because of the surfactant action of the lecithin and EO that may help in the diffusion of drug. The histopathological data showed that EO-lecithin organogels were safe enough for the topical purpose. Hence, the present lecithin based organogel appears beneficial for topical delivery of fluconazole in terms of easy preparation, safety, stability and low cost.

S4(13)-PV cell-penetrating peptide induces physical and morphological changes in membrane-mimetic lipid systems and cell membranes: implications for cell internalization.

PubMed

Cardoso, Ana M S; Trabulo, Sara; Cardoso, Ana L; Lorents, Annely; Morais, Catarina M; Gomes, Paula; Nunes, Cláudia; Lúcio, Marlene; Reis, Salette; Padari, Kärt; Pooga, Margus; Pedroso de Lima, Maria C; Jurado, Amália S

2012-03-01

The present work aims to gain insights into the role of peptide-lipid interactions in the mechanisms of cellular internalization and endosomal escape of the S4(13)-PV cell-penetrating peptide, which has been successfully used in our laboratory as a nucleic acid delivery system. A S4(13)-PV analogue, S4(13)-PVscr, displaying a scrambled amino acid sequence, deficient cell internalization and drug delivery inability, was used in this study for comparative purposes. Differential scanning calorimetry, fluorescence polarization and X-ray diffraction at small and wide angles techniques showed that both peptides interacted with anionic membranes composed of phosphatidylglycerol or a mixture of this lipid with phosphatidylethanolamine, increasing the lipid order, shifting the phase transition to higher temperatures and raising the correlation length between the bilayers. However, S4(13)-PVscr, in contrast to the wild-type peptide, did not promote lipid domain segregation and induced the formation of an inverted hexagonal lipid phase instead of a cubic phase in the lipid systems assayed. Electron microscopy showed that, as opposed to S4(13)-PVscr, the wild-type peptide induced the formation of a non-lamellar organization in membranes of HeLa cells. We concluded that lateral phase separation and destabilization of membrane lamellar structure without compromising membrane integrity are on the basis of the lipid-driven and receptor-independent mechanism of cell entry of S4(13)-PV peptide. Overall, our results can contribute to a better understanding of the role of peptide-lipid interactions in the mechanisms of cell-penetrating peptide membrane translocation, helping in the future design of more efficient cell-penetrating peptide-based drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Self-assembling complexes between binary mixtures of lipids with different linkers and nucleic acids promote universal mRNA, DNA and siRNA delivery.

PubMed

Colombani, Thibault; Peuziat, Pauline; Dallet, Laurence; Haudebourg, Thomas; Mével, Mathieu; Berchel, Mathieu; Lambert, Olivier; Habrant, Damien; Pitard, Bruno

2017-03-10

Protein expression and RNA interference require efficient delivery of DNA or mRNA and small double stranded RNA into cells, respectively. Although cationic lipids are the most commonly used synthetic delivery vectors, a clear need still exists for a better delivery of various types of nucleic acids molecules to improve their biological activity. To optimize the transfection efficiency, a molecular approach consisting in modifying the chemical structure of a given cationic lipid is usually performed, but an alternative strategy could rely on modulating the supramolecular assembly of lipidic lamellar phases sandwiching the nucleic acids molecules. To validate this new concept, we synthesized on one hand two paromomycin-based cationic lipids, with either an amide or a phosphoramide linker, and on the other hand two imidazole-based neutral lipids, having as well either an amide or a phosphoramide function as linker. Combinations of cationic and helper lipids containing the same amide or phosphoramide linkers led to the formation of homogeneous lamellar phases, while hybrid lamellar phases were obtained when the linkers on the cationic and helper lipids were different. Cryo-transmission electron microscopy and fluorescence experiments showed that liposomes/nucleic acids complexes resulting from the association of nucleic acids with hybrid lamellar phases led to complexes that were more stable in the extracellular compartment compared to those obtained with homogeneous systems. In addition, we observed that the most active supramolecular assemblies for the delivery of DNA, mRNA and siRNA were obtained when the cationic and helper lipids possess linkers of different natures. The results clearly show that this supramolecular strategy modulating the property of the lipidic lamellar phase constitutes a new approach for increasing the delivery of various types of nucleic acid molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent.

PubMed

Qin, Lingzhen; Mei, Liling; Shan, Ziyun; Huang, Ying; Pan, Xin; Li, Ge; Gu, Yukun; Wu, Chuanbin

2016-01-01

Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol-solvent-water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48 h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.

Menstrual cycle phase modulates reward-related neural function in women.

PubMed

Dreher, Jean-Claude; Schmidt, Peter J; Kohn, Philip; Furman, Daniella; Rubinow, David; Berman, Karen Faith

2007-02-13

There is considerable evidence from animal studies that the mesolimbic and mesocortical dopamine systems are sensitive to circulating gonadal steroid hormones. Less is known about the influence of estrogen and progesterone on the human reward system. To investigate this directly, we used functional MRI and an event-related monetary reward paradigm to study women with a repeated-measures, counterbalanced design across the menstrual cycle. Here we show that during the midfollicular phase (days 4-8 after onset of menses) women anticipating uncertain rewards activated the orbitofrontal cortex and amygdala more than during the luteal phase (6-10 days after luteinizing hormone surge). At the time of reward delivery, women in the follicular phase activated the midbrain, striatum, and left fronto-polar cortex more than during the luteal phase. These data demonstrate augmented reactivity of the reward system in women during the midfollicular phase when estrogen is unopposed by progesterone. Moreover, investigation of between-sex differences revealed that men activated ventral putamen more than women during anticipation of uncertain rewards, whereas women more strongly activated the anterior medial prefrontal cortex at the time of reward delivery. Correlation between brain activity and gonadal steroid levels also revealed that the amygdalo-hippocampal complex was positively correlated with estradiol level, regardless of menstrual cycle phase. Together, our findings provide evidence of neurofunctional modulation of the reward system by gonadal steroid hormones in humans and establish a neurobiological foundation for understanding their impact on vulnerability to drug abuse, neuropsychiatric diseases with differential expression across males and females, and hormonally mediated mood disorders.

Determination of prospective displacement-based gate threshold for respiratory-gated radiation delivery from retrospective phase-based gate threshold selected at 4D CT simulation.

PubMed

Vedam, S; Archambault, L; Starkschall, G; Mohan, R; Beddar, S

2007-11-01

Four-dimensional (4D) computed tomography (CT) imaging has found increasing importance in the localization of tumor and surrounding normal structures throughout the respiratory cycle. Based on such tumor motion information, it is possible to identify the appropriate phase interval for respiratory gated treatment planning and delivery. Such a gating phase interval is determined retrospectively based on tumor motion from internal tumor displacement. However, respiratory-gated treatment is delivered prospectively based on motion determined predominantly from an external monitor. Therefore, the simulation gate threshold determined from the retrospective phase interval selected for gating at 4D CT simulation may not correspond to the delivery gate threshold that is determined from the prospective external monitor displacement at treatment delivery. The purpose of the present work is to establish a relationship between the thresholds for respiratory gating determined at CT simulation and treatment delivery, respectively. One hundred fifty external respiratory motion traces, from 90 patients, with and without audio-visual biofeedback, are analyzed. Two respiratory phase intervals, 40%-60% and 30%-70%, are chosen for respiratory gating from the 4D CT-derived tumor motion trajectory. From residual tumor displacements within each such gating phase interval, a simulation gate threshold is defined based on (a) the average and (b) the maximum respiratory displacement within the phase interval. The duty cycle for prospective gated delivery is estimated from the proportion of external monitor displacement data points within both the selected phase interval and the simulation gate threshold. The delivery gate threshold is then determined iteratively to match the above determined duty cycle. The magnitude of the difference between such gate thresholds determined at simulation and treatment delivery is quantified in each case. Phantom motion tests yielded coincidence of simulation and delivery gate thresholds to within 0.3%. For patient data analysis, differences between simulation and delivery gate thresholds are reported as a fraction of the total respiratory motion range. For the smaller phase interval, the differences between simulation and delivery gate thresholds are 8 +/- 11% and 14 +/- 21% with and without audio-visual biofeedback, respectively, when the simulation gate threshold is determined based on the mean respiratory displacement within the 40%-60% gating phase interval. For the longer phase interval, corresponding differences are 4 +/- 7% and 8 +/- 15% with and without audiovisual biofeedback, respectively. Alternatively, when the simulation gate threshold is determined based on the maximum average respiratory displacement within the gating phase interval, greater differences between simulation and delivery gate thresholds are observed. A relationship between retrospective simulation gate threshold and prospective delivery gate threshold for respiratory gating is established and validated for regular and nonregular respiratory motion. Using this relationship, the delivery gate threshold can be reliably estimated at the time of 4D CT simulation, thereby improving the accuracy and efficiency of respiratory-gated radiation delivery.

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

PubMed

Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

2017-01-01

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

PubMed Central

Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

2017-01-01

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. PMID:28243062

An evolutionary approach to the architecture of effective healthcare delivery systems.

PubMed

Towill, D R; Christopher, M

2005-01-01

Aims to show that material flow concepts developed and successfully applied to commercial products and services can form equally well the architectural infrastructure of effective healthcare delivery systems. The methodology is based on the "power of analogy" which demonstrates that healthcare pipelines may be classified via the Time-Space Matrix. A small number (circa 4) of substantially different healthcare delivery pipelines will cover the vast majority of patient needs and simultaneously create adequate added value from their perspective. The emphasis is firmly placed on total process mapping and analysis via established identification techniques. Healthcare delivery pipelines must be properly engineered and matched to life cycle phase if the service is to be effective. This small family of healthcare delivery pipelines needs to be designed via adherence to very specific-to-purpose principles. These vary from "lean production" through to "agile delivery". The proposition for a strategic approach to healthcare delivery pipeline design is novel and positions much currently isolated research into a comprehensive organisational framework. It therefore provides a synthesis of the needs of global healthcare.

Numerical Comparison of Nasal Aerosol Administration Systems for Efficient Nose-to-Brain Drug Delivery.

PubMed

Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Chan, Hak-Kim; Tu, Jiyuan

2017-12-29

Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

75 FR 22810 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... System (EHRDS)--practice application and profile update system; Use: In 2008, the Secretary of the... new demonstration initiative using Medicare waiver authority to reward the delivery of high-quality... system was first developed with the intention of having practices applying to participate in Phase 2 of...

75 FR 41487 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

...: Electronic Health Records Demonstration System (EHRDS)--practice application and profile update system; Use... reward the delivery of high-quality care supported by the adoption and use of electronic health records... demonstration system was first developed with the intention of having practices applying to participate in Phase...

Regional freight information resources for market opportunities in the Great Lakes maritime transportation system : phase II.

DOT National Transportation Integrated Search

2009-11-01

The Great Lakes Maritime Information Delivery System (GLMIDS) is designed to facilitate the acquisition, storage, management, analysis and exchange of data between analysts and decision-makers within maritime commerce. (See http://maritime.utoledo.ed...

Efficacy of nano- and microemulsion-based topical gels in delivery of ibuprofen: an in vivo study.

PubMed

Azizi, Mosayeb; Esmaeili, Fariba; Partoazar, Alireza; Ejtemaei Mehr, Shahram; Amani, Amir

2017-03-01

Nanoemulsion has shown many advantages in drug delivery systems. In this study, for the first time, analgesic and anti-inflammatory properties of a nanomelusion of almond oil with and without ibuprofen was compared with corresponding microemulsion and commercial topical gel of the drug using formalin and carrageenan tests, respectively. Almond oil (oil phase) was mixed with Tween 80 and Span 80 (surfactants), and ethanol (co-surfactant) and them distilled water (aqueous phase) was then added to the mixture at once. Prepared nanoemulsions were pre-emulsified into a 100 ml beaker using magnet/stirrer (1000 rpm). Then, using a probe ultrasonicator (Hielscher UP400s, Hielscher, Ringwood, NJ) the nanoemulsions were formed. The optimised nanoemulsion formulation containing 2.5% ibuprofen, showed improved analgesic and anti-inflammatory effects compared with commercial product and corresponding microemulsion product containing 5% ibuprofen (i.e. twice the content of ibuprofen in the nanoemulsion) in vivo. The nanoemulsion preparation showed superior analgesic activities during chronic phase. Also, it decreased the inflammation from the first hour, while the microemulsion and the commercial product started to show their anti-inflammatory effects after 2 and 3 h, respectively. Our finding suggests that the size of the emulsion particles must be considered as an important factor in topical drug delivery systems.

Self-nanoemulsifying drug-delivery system for improved oral bioavailability of rosuvastatin using natural oil antihyperlipdemic.

PubMed

Abo Enin, Hadel A

2015-01-01

The aim is improving the antihyperlipidemic activity of Rosuvastatin Calcium (Rs) through improving its solubility using self-nanoemulsifying drug delivery system (SNEDDS) containing natural oil full of unsaturated fatty acid and omega 3. A 7 × 3(2) full factorial design was adopted for optimization of oil ratio, Surfactant: Co-surfactant (S:CoS) ratio and oil:S/CoS ratio. Ternary phase diagrams were constructed for optimizing the system with drug loading (10 and 20%). The optimized SNEDD systems were evaluated according to their physical evaluation and drug release. Furthermore, the anti-hyperlipidemia efficacy was compared with commercially marketed product on rates followed by clinical study. The system containing Tween 80:PEG 400 (3:1) and olive oil:garlic oil (1:1) as an oily phase has droplet size less than 100 nm, ZP (+23.43 ± 2.58 mV), PDI (<0.02) and cloud point (>90 °C). In vitro drug release studies showed remarkable enhancement of the Rs release from Rs-SNEDDS. The antihyperlipidemic effect of Rs-SNEDDS is greater than that of the commercial tablets and the pure drug on rates and in hyperlipidemic patients. Rs-SNEDDS is a promising drug delivery system for improving the drug solubility and antihyperlipidemic effect using natural oils as (olive oil and garlic oil).

A phase 1, randomized, controlled dose-escalation study of EP-1300 polyepitope DNA vaccine against Plasmodium falciparum malaria administered via electroporation.

PubMed

Spearman, Paul; Mulligan, Mark; Anderson, Evan J; Shane, Andi L; Stephens, Kathy; Gibson, Theda; Hartwell, Brooke; Hannaman, Drew; Watson, Nora L; Singh, Karnail

2016-11-04

Plasmodium falciparum malaria is one of the leading infectious causes of childhood mortality in Africa. EP-1300 is a polyepitope plasmid DNA vaccine expressing 38 cytotoxic T cell epitopes and 16 helper T cell epitopes derived from P. falciparum antigens expressed predominantly in the liver phase of the parasite's life cycle. We performed a phase 1 randomized, placebo-controlled, dose escalation clinical trial of the EP-1300 DNA vaccine administered via electroporation using the TriGrid Delivery System device (Ichor Medical Systems). Although the delivery of the EP-1300 DNA vaccine via electroporation was safe, tolerability was less than that usually observed with standard needle and syringe intramuscular administration. This was primarily due to acute local discomfort at the administration site during electroporation. Despite the use of electroporation, the vaccine was poorly immunogenic. The reasons for the poor immunogenicity of this polyepitope DNA vaccine remain uncertain. ClinicalTrials.gov NCT01169077. Copyright © 2016 Elsevier Ltd. All rights reserved.

Determination of prospective displacement-based gate threshold for respiratory-gated radiation delivery from retrospective phase-based gate threshold selected at 4D CT simulation

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

Vedam, S.; Archambault, L.; Starkschall, G.

2007-11-15

Four-dimensional (4D) computed tomography (CT) imaging has found increasing importance in the localization of tumor and surrounding normal structures throughout the respiratory cycle. Based on such tumor motion information, it is possible to identify the appropriate phase interval for respiratory gated treatment planning and delivery. Such a gating phase interval is determined retrospectively based on tumor motion from internal tumor displacement. However, respiratory-gated treatment is delivered prospectively based on motion determined predominantly from an external monitor. Therefore, the simulation gate threshold determined from the retrospective phase interval selected for gating at 4D CT simulation may not correspond to the deliverymore » gate threshold that is determined from the prospective external monitor displacement at treatment delivery. The purpose of the present work is to establish a relationship between the thresholds for respiratory gating determined at CT simulation and treatment delivery, respectively. One hundred fifty external respiratory motion traces, from 90 patients, with and without audio-visual biofeedback, are analyzed. Two respiratory phase intervals, 40%-60% and 30%-70%, are chosen for respiratory gating from the 4D CT-derived tumor motion trajectory. From residual tumor displacements within each such gating phase interval, a simulation gate threshold is defined based on (a) the average and (b) the maximum respiratory displacement within the phase interval. The duty cycle for prospective gated delivery is estimated from the proportion of external monitor displacement data points within both the selected phase interval and the simulation gate threshold. The delivery gate threshold is then determined iteratively to match the above determined duty cycle. The magnitude of the difference between such gate thresholds determined at simulation and treatment delivery is quantified in each case. Phantom motion tests yielded coincidence of simulation and delivery gate thresholds to within 0.3%. For patient data analysis, differences between simulation and delivery gate thresholds are reported as a fraction of the total respiratory motion range. For the smaller phase interval, the differences between simulation and delivery gate thresholds are 8{+-}11% and 14{+-}21% with and without audio-visual biofeedback, respectively, when the simulation gate threshold is determined based on the mean respiratory displacement within the 40%-60% gating phase interval. For the longer phase interval, corresponding differences are 4{+-}7% and 8{+-}15% with and without audio-visual biofeedback, respectively. Alternatively, when the simulation gate threshold is determined based on the maximum average respiratory displacement within the gating phase interval, greater differences between simulation and delivery gate thresholds are observed. A relationship between retrospective simulation gate threshold and prospective delivery gate threshold for respiratory gating is established and validated for regular and nonregular respiratory motion. Using this relationship, the delivery gate threshold can be reliably estimated at the time of 4D CT simulation, thereby improving the accuracy and efficiency of respiratory-gated radiation delivery.« less

Manufacturing Techniques and Surface Engineering of Polymer Based Nanoparticles for Targeted Drug Delivery to Cancer

PubMed Central

Wang, Yichao; Li, Puwang; Truong-Dinh Tran, Thao; Zhang, Juan; Kong, Lingxue

2016-01-01

The evolution of polymer based nanoparticles as a drug delivery carrier via pharmaceutical nano/microencapsulation has greatly promoted the development of nano- and micro-medicine in the past few decades. Poly(lactide-co-glycolide) (PLGA) and chitosan, which are biodegradable and biocompatible polymers, have been approved by both the Food & Drug Administration (FDA) and European Medicine Agency (EMA), making them ideal biomaterials that can be advanced from laboratory development to clinical oral and parental administrations. PLGA and chitosan encapsulated nanoparticles (NPs) have successfully been developed as new oral drug delivery systems with demonstrated high efficacy. This review aims to provide a comprehensive overview of the fabrication of PLGA and chitosan particulate systems using nano/microencapsulation methods, the current progress and the future outlooks of the nanoparticulate drug delivery systems. Especially, we focus on the formulations and nano/micro-encapsulation techniques using top-down techniques. It also addresses how the different phases including the organic and aqueous ones in the emulsion system interact with each other and subsequently influence the properties of the drug delivery system. Besides, surface modification strategies which can effectively engineer intrinsic physicochemical properties are summarised. Finally, future perspectives and potential directions of PLGA and chitosan nano/microencapsulated drug systems are outlined. PMID:28344283

Gold nanorods in an oil-base formulation for transdermal treatment of type 1 diabetes in mice

NASA Astrophysics Data System (ADS)

Nose, Keisuke; Pissuwan, Dakrong; Goto, Masahiro; Katayama, Yoshiki; Niidome, Takuro

2012-05-01

Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients.Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr30651d

BOA: Asbestos pipe-insulation removal robot system, Phase 2. Topical report, January--June 1995

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

Schempf, H.; Bares, J.E.

This report explored the regulatory impact and cost-benefit of a robotic thermal asbestos pipe-insulation removal system over the current manual abatement work practice. The authors are currently in the second phase of a two-phase program to develop a robotic asbestos abatement system, comprised of a ground-based support system (including vacuum, fluid delivery, computing/electronics/power, and other subsystems) and several on-pipe removal units, each sized to handle pipes within a given diameter range. The intent of this study was to (i) aid in developing design and operational criteria for the overall system to maximize cost-efficiency, and (ii) to determine the commercial potentialmore » of a robotic pipe-insulation abatement system.« less

Cubosomes as targeted drug delivery systems - a biopharmaceutical approach.

PubMed

Lakshmi, Naga M; Yalavarthi, Prasanna R; Vadlamudi, Harini C; Thanniru, Jyotsna; Yaga, Gowri; K, Haritha

2014-01-01

Cubosomes are reversed bicontinuous cubic phases and possess unique physicochemical properties. These special systems are receiving much attention for the delivery of various hydrophilic, hydrophobic and amphiphilic drugs with enhanced bioavailability and high loading capacity. A wide variety of drugs are applicable for cubosome formulation for various routes of delivery. The lipids used in cubosome formulation are more stable and offer stability to the formulation during shelf-life. The article reviews about the back ground, techniques of cubosome preparation such as high pressure homogenization, probe ultrasonication and automated cubosome preparation; and also methods of cubosomes preparation such as top down, bottom up and other methods with pictorial presentation. This article emphasizes the phase transition and also targeted approaches of cubosomes. The characterization studies for cubosomes such as cryo transmission electron microscopy, differential scanning calorimetry and scanning electron microscopy followed by in-vitro and in-vivo evaluation studies of cubosomes were explained with appropriate examples. Recent applications of cubosomes were explained with reference to flurbiprofen, odorranalectin, diazepam and dexamethasone. The advantages, disadvantages and limitations of cubosomal technology were emphasized.

Consistency and Reproducibility of Bioaerosol Delivery for Infectivity Studies on Mice

DTIC Science & Technology

2010-03-01

respiration, the most common being the common laboratory rat (strains of Rattus norvegicus) and mouse ( Mus musculus ). Animal respiratory systems are...validation U U U UU 92 Joseph D. Wander Reset CONSISTENCY AND REPRODUCIBILITY OF BIOAEROSOL DELIVERY FOR INFECTIVITY STUDIES ON MICE...design and construction phase of the project. The data from this thesis appear as part of the US Air Force Research Laboratory technical report AFRL

Driving Circuitry for Focused Ultrasound Noninvasive Surgery and Drug Delivery Applications

PubMed Central

El-Desouki, Munir M.; Hynynen, Kullervo

2011-01-01

Recent works on focused ultrasound (FUS) have shown great promise for cancer therapy. Researchers are continuously trying to improve system performance, which is resulting in an increased complexity that is more apparent when using multi-element phased array systems. This has led to significant efforts to reduce system size and cost by relying on system integration. Although ideas from other fields such as microwave antenna phased arrays can be adopted in FUS, the application requirements differ significantly since the frequency range used in FUS is much lower. In this paper, we review recent efforts to design efficient power monitoring, phase shifting and output driving techniques used specifically for high intensity focused ultrasound (HIFU). PMID:22346589

Driving circuitry for focused ultrasound noninvasive surgery and drug delivery applications.

PubMed

El-Desouki, Munir M; Hynynen, Kullervo

2011-01-01

Recent works on focused ultrasound (FUS) have shown great promise for cancer therapy. Researchers are continuously trying to improve system performance, which is resulting in an increased complexity that is more apparent when using multi-element phased array systems. This has led to significant efforts to reduce system size and cost by relying on system integration. Although ideas from other fields such as microwave antenna phased arrays can be adopted in FUS, the application requirements differ significantly since the frequency range used in FUS is much lower. In this paper, we review recent efforts to design efficient power monitoring, phase shifting and output driving techniques used specifically for high intensity focused ultrasound (HIFU).

Nanoemulsion-based delivery systems for polyunsaturated (ω-3) oils: formation using a spontaneous emulsification method.

PubMed

Gulotta, Alessandro; Saberi, Amir Hossein; Nicoli, Maria Cristina; McClements, David Julian

2014-02-19

Nanoemulsion-based delivery systems are finding increasing utilization to encapsulate lipophilic bioactive components in food, personal care, cosmetic, and pharmaceutical applications. In this study, a spontaneous emulsification method was used to fabricate nanoemulsions from polyunsaturated (ω-3) oils, that is, fish oil. This low-energy method relies on formation of fine oil droplets when an oil/surfactant mixture is added to an aqueous solution. The influence of surfactant-to-oil ratio (SOR), oil composition (lemon oil and MCT), and cosolvent composition (glycerol, ethanol, propylene glycol, and water) on the formation and stability of the systems was determined. Optically transparent nanoemulsions could be formed by controlling SOR, oil composition, and aqueous phase composition. The spontaneous emulsification method therefore has considerable potential for fabricating nanoemulsion-based delivery systems for incorporating polyunsatured oils into clear food, personal care, and pharmaceutical products.

Anti-Inflammatory Activity of Babassu Oil and Development of a Microemulsion System for Topical Delivery

PubMed Central

Reis, Mysrayn Y. F. A.; dos Santos, Simone M.; Silva, Danielle R.; Navarro, Daniela M. A. Ferraz; Santos, Geanne K. N.; Hallwass, Fernando; Bianchi, Otávio; Silva, Alexandre G.; Melo, Janaína V.; Machado, Giovanna; Saraiva, Karina L. A.

2017-01-01

Babassu oil extraction is the main income source in nut breakers communities in northeast of Brazil. Among these communities, babassu oil is used for cooking but also medically to treat skin wounds and inflammation, and vulvovaginitis. This study aimed to evaluate the anti-inflammatory activity of babassu oil and develop a microemulsion system with babassu oil for topical delivery. Topical anti-inflammatory activity was evaluated in mice ear edema using PMA, arachidonic acid, ethyl phenylpropiolate, phenol, and capsaicin as phlogistic agents. A microemulsion system was successfully developed using a Span® 80/Kolliphor® EL ratio of 6 : 4 as the surfactant system (S), propylene glycol and water (3 : 1) as the aqueous phase (A), and babassu oil as the oil phase (O), and analyzed through conductivity, SAXS, DSC, TEM, and rheological assays. Babassu oil and lauric acid showed anti-inflammatory activity in mice ear edema, through inhibition of eicosanoid pathway and bioactive amines. The developed formulation (39% A, 12.2% O, and 48.8% S) was classified as a bicontinuous to o/w transition microemulsion that showed a Newtonian profile. The topical anti-inflammatory activity of microemulsified babassu oil was markedly increased. A new delivery system of babassu microemulsion droplet clusters was designed to enhance the therapeutic efficacy of vegetable oil. PMID:29430254

Lunar Cycle Influences Spontaneous Delivery in Cows

PubMed Central

Yonezawa, Tomohiro; Uchida, Mona; Tomioka, Michiko; Matsuki, Naoaki

2016-01-01

There is a popular belief that the lunar cycle influences spontaneous delivery in both humans and cattle. To assess this relationship, we investigated the synodic distribution of spontaneous deliveries in domestic Holstein cows. We used retrospective data from 428 spontaneous, full-term deliveries within a three-year period derived from the calving records of a private farm in Hokkaido, Japan. Spontaneous birth frequency increased uniformly from the new moon to the full moon phase and decreased until the waning crescent phase. There was a statistically significant peak between the waxing gibbous and full moon phases compared with those between the last quarter and the waning crescent. These changes were clearly observed in deliveries among multiparous cows, whereas they were not evident in deliveries among nulliparous cows. These data suggest the utility of dairy cows as models for bio-meteorological studies, and indicate that monitoring lunar phases may facilitate comprehensive understanding of parturition. PMID:27580019

Zein-based Nanocarriers as Potential Natural Alternatives for Drug and Gene Delivery: Focus on Cancer Therapy.

PubMed

Elzoghby, Ahmed; Freag, May; Mamdouh, Hadeer; Elkhodairy, Kadria

2017-01-01

Protein nanocarriers possess unique merits including minimal cytotoxicity, numerous renewable sources, and high drug-binding capability. In opposition to delivery carriers utilizing hydrophilic animal proteins, hydrophobic plant proteins (e.g, zein) have great tendency in fabricating controlled-release particulate carriers without additional chemical modification to stiffen them, which in turn evades the use of toxic chemical crosslinkers. Moreover, zein is related to a class of alcohol-soluble prolamins and generally recognized as safe (GRAS) carrier for drug delivery. Various techniques have been adopted to fabricate zein-based nanoparticulate systems including phase separation coacervation, spray-drying, supercritical anti-solvent approach, electrospinning and self-assembly. This manuscript reviews the recent advances in the zein-based colloidal nano-carrier systems such as nanospheres, nanocapsules, micelles and nanofibers with a special focus on their physicochemical characteristics and drug delivery applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Formulation and characterization of liquid crystal systems containing azelaic acid for topical delivery.

PubMed

Aytekin, Merve; Gursoy, R Neslihan; Ide, Semra; Soylu, Elif H; Hekimoglu, Sueda

2013-02-01

The aim of this study is to prepare and characterize azelaic acid (AzA) containing liquid crystal (LC) drug delivery systems for topical use. Two ternary phase diagrams, containing liquid paraffin as the oil component and a mixture of two nonionic surfactants (Brij 721P and Brij 72), were constructed. Formulations chosen from the phase diagrams were characterized by polarized light microscopy, rheological analyses, differential scanning calorimetry (DSC), and small angle x-ray scattering spectroscopy. Polarized light microscopy proved that except the oil/water emulsion (O/W E), other formulations showed lamellar LC structure. In vitro release studies indicated that the fastest release was achieved by the Lamellar LC (LLC) and O/W E systems, whereas slower release was obtained from the emulsion containing lamellar LC (E-LLC) and distorted lamellar LC (D-LLC) systems. Results of rheological measurements both supported the results of in vitro release studies and showed that the emulsion containing the LC (E-LLC) system had the most stable structure. The formulations and their effect on stratum corneum (SC) were evaluated by DSC studies. The lamellar LC (LLC), emulsion containing lamellar liquid crystal (E-LLC), and O/W E formulations had an effect on both lipid and protein components of SC, whereas distorted lamellar liquid crystal (D-LLC) system had an effect on only the lipid components of SC. LLC systems could be considered promising for the topical delivery of AzA.

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

PubMed

Ye, Bai-Liang; Zheng, Ru; Ruan, Xiao-Jiao; Zheng, Zhi-Hai; Cai, Hua-Jie

2018-01-01

Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Solving multi-customer FPR model with quality assurance and discontinuous deliveries using a two-phase algebraic approach.

PubMed

Chiu, Yuan-Shyi Peter; Chou, Chung-Li; Chang, Huei-Hsin; Chiu, Singa Wang

2016-01-01

A multi-customer finite production rate (FPR) model with quality assurance and discontinuous delivery policy was investigated in a recent paper (Chiu et al. in J Appl Res Technol 12(1):5-13, 2014) using differential calculus approach. This study employs mathematical modeling along with a two-phase algebraic method to resolve such a specific multi-customer FPR model. As a result, the optimal replenishment lot size and number of shipments can be derived without using the differential calculus. Such a straightforward method may assist practitioners who with insufficient knowledge of calculus in learning and managing the real multi-customer FPR systems more effectively.

Drug Delivery in Cancer Therapy, Quo Vadis?

PubMed

Lu, Zheng-Rong; Qiao, Peter

2018-03-22

The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody-drug conjugates, liposomes, polymer-drug conjugates, polymer implants, micelles, and nanoparticles. The clinical outcomes of these delivery systems from various phases of clinical trials are summarized. The success and limitations of the drug delivery strategies are discussed based on the clinical observations. In addition, the challenges in applying drug delivery for efficacious cancer therapy, including physical barriers, tumor heterogeneity, drug resistance, and metastasis, are discussed along with future perspectives of drug delivery in cancer therapy. In doing so, we intend to underscore that efficient delivery of cancer therapeutics to solid malignancies remains a major challenge in cancer therapy, and requires a multidisciplinary approach that integrates knowledge from the diverse fields of chemistry, biology, engineering, and medicine. The overall objective of this review is to improve our understanding of the clinical fate of commonly investigated drug delivery strategies, and to identify the limitations that must be addressed in future drug delivery strategies, toward the pursuit of curative therapies for cancer.

[Remarks Prepared for Delivery to the National School Boards Association.

ERIC Educational Resources Information Center

Bond, Julian

The history of the twenty-five year period since the Brown v. Board of Education decision can be divided into three phases. The first phase was from '54 to '64, during which the Court applied its rule of "all deliberate speed." The focus was on desegregating the dual systems of the South, the products of de jure segregation, and all…

The Children's Services Delivery System in California: Preliminary Report--Phase I.

ERIC Educational Resources Information Center

Commission on California State Government Organization and Economy, Sacramento.

Concerned because California now annually administers an estimated $5.9 billion in funding for children's services programs, the Little Hoover Commission initiated a study on the state's provision for children's services. This report, on Phase I of the study, identifies the extent of the problem in 23 findings and provides a plan of action in 15…

Constellation Program Thermal and Environmental Control and Life Support System Status: 2009 - 2010

NASA Technical Reports Server (NTRS)

Williams, David E.; Carrasquillo, Robyn L.; Bagdigian, Robert M.

2009-01-01

The Constellation Program (CxP) consists of spacecrafts, launch vehicles, and support systems to execute the Exploration Architecture. The Program is currently divided into three distinct phases. The first phase is to develop a vehicle to provide limited cargo resupply capability and allow crew member rotation to the International Space Station (ISS). The second phase is to support the return of humans to the moon. The final phase is currently envisioned to allow the delivery of humans and cargo to Mars for an extended time. To implement this phased approach the CxP is currently working on the first vehicle and support systems to replace the Space Shuttle and allow continued access to space. This paper provides a summary of the CxP Thermal and Environmental Control and Life Support (ECLS) work that that has occurred across the different parts of the Program in support of these three phases over the past year.

IDC System Specification Document Version 1.1.

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

Harris, James M.; Lober, Randall R.

2015-02-01

This document contains the system specifications derived to satisfy the system requirements found in the IDC System Requirements Document for the IDC Reengineering Phase 2 project. Revisions Version Date Author/Team Revision Description Authorized by V1.0 12/2014 IDC Reengineering Project Team Initial delivery M. Harris V1.1 2/2015 IDC Reengineering Project Team Iteration I2 Review Comments M. Harris

Combined effects of the drug distribution and mucus diffusion properties of self-microemulsifying drug delivery systems on the oral absorption of fenofibrate.

PubMed

Sunazuka, Yushi; Ueda, Keisuke; Higashi, Kenjirou; Tanaka, Yusuke; Moribe, Kunikazu

2018-05-24

We present the absorption improvement mechanism of fenofibrate (FFB), a Biopharmaceutics Classification System (BCS) class II drug, from self-microemulsifying drug delivery systems (SMEDDS), centered on improving the diffusion of FFB through the unstirred water layer (UWL). Four SMEDDS formulations containing Labrafac™ lipophile WL 1349 (WL1349) or Labrafil ® M 1944CS (M1944) oils and NIKKOL HCO-40 (HCO40) or NIKKOL HCO-60 (HCO60) surfactants were prepared. Every SMEDDS formulation formed microemulsion droplets of approximately 30 nm. In vitro tests showed that the microemulsion droplets containing M1944 had relatively small FFB solubilization capacities, causing larger amounts of FFB to be dissolved in the bulk water phase, compared to the droplets containing WL1349. The diffusivity of the microemulsion droplets through the mucin solution layer was enhanced when using HCO40 compared to HCO60. The oral absorption in rats was the highest when using the SMEDDS formulation containing M1944 and HCO40. High FFB distribution in the bulk water phase and fast diffusion of microemulsion droplets through the mucus layer contributed to the efficient delivery of FFB molecules through the UWL to the epithelial cells, leading to enhanced FFB absorption. Copyright © 2018 Elsevier B.V. All rights reserved.

Phase-shift, stimuli-responsive drug carriers for targeted delivery

PubMed Central

O’Neill, Brian E; Rapoport, Natalya

2011-01-01

The intersection of particles and directed energy is a rich source of novel and useful technology that is only recently being realized for medicine. One of the most promising applications is directed drug delivery. This review focuses on phase-shift nanoparticles (that is, particles of submicron size) as well as micron-scale particles whose action depends on an external-energy triggered, first-order phase shift from a liquid to gas state of either the particle itself or of the surrounding medium. These particles have tremendous potential for actively disrupting their environment for altering transport properties and unloading drugs. This review covers in detail ultrasound and laser-activated phase-shift nano- and micro-particles and their use in drug delivery. Phase-shift based drug-delivery mechanisms and competing technologies are discussed. PMID:22059114

Microemulsion Using Polyoxyethylene Sorbitan Trioleate and its Usage for Skin Delivery of Resveratrol to Protect Skin against UV-Induced Damage.

PubMed

Yutani, Reiko; Teraoka, Reiko; Kitagawa, Shuji

2015-01-01

We examined the phase behavior of various polyoxyethylene sorbitan fatty acid ester (polysorbates)/ethanol/isopropyl myristate (IPM)/150 mM NaCl solution (NaClaq) systems in order to prepare a microemulsion containing a low ratio of ethanol, which is more suitable for in vivo application. Using polyoxyethylene sorbitan trioleate (Tween 85), which has a large lipophilic moiety, as a surfactant component, single-phase domain of the phase diagram was the largest of all the polysorbates examined, and in particular a large oil-rich single-phase domain was obtained. When the ratio of Tween 85 to ethanol was changed from 1 : 1 to 3 : 1, the oil-rich single-phase domain further expanded, which led to a reduced ethanol concentration in the preparation. Thus, we determined the composition of the microemulsion to be Tween 85 : ethanol : IPM : NaClaq=30 : 10 : 53 : 7, and used it for skin delivery of resveratrol. Microemulsion gel was also prepared by adding 6.5% Aerosil) 200 into the microemulsion for ease of topical application. When applied with each vehicle, delivery of resveratrol into guinea pig skin in vitro was significantly enhanced compared with that by IPM, and resveratrol incorporated into the skin by microemulsion gel decreased lipid peroxidation to 29.5% compared with that of the control. Pretreatment of guinea pig dorsal skin with the microemulsion gel containing resveratrol almost completely prevented UV-B-induced erythema formation in vivo. These findings demonstrate that the microemulsion using Tween 85 containing a minimal concentration of ethanol enhanced the skin delivery of resveratrol and the incorporated resveratrol exhibited a protective effect against UV-induced oxidative damage.

Lecithin-linker formulations for self-emulsifying delivery of nutraceuticals.

PubMed

Chu, Jacquelene; Cheng, Yu-Ling; Rao, A Venketeshwer; Nouraei, Mehdi; Zarate-Muñoz, Silvia; Acosta, Edgar J

2014-08-25

Lecithin-linker microemulsions are formulations produced with soybean lecithin in combination with a highly lipophilic (lipophilic linker) and highly hydrophilic (hydrophilic linkers) surfactant-like additives. In this work, lecithin-linker systems were formulated to produce self-emulsifying delivery systems for β-carotene and β-sitosterol. The concentration of the lipophilic linker, sorbitan monooleate, was adjusted to minimize the formation of liquid crystals. The concentration of hydrophilic linkers, decaglyceryl caprylate/caprate and PEG-6-caprylic/capric glycerides, was gradually increased (scanned) until single phase clear microemulsions were obtained. For these scans, the oil (ethyl caprate) to water ratio was set to 1. The single phase, clear microemulsions were diluted with fed-state simulated intestinal fluid (FeSSIF) and produced stable emulsions, with drop sizes close to 200 nm. Using pseudo-ternary phase diagrams to evaluate the process of dilution of microemulsion preconcentrates (mixtures of oil, lecithin and linkers with little or no water) with FeSSIF, it was determined that self-emulsifying systems are obtained when the early stages of the dilution produce single phase microemulsions. If liquid crystals or multiple phase systems are obtained during those early stages, then the emulsification yields unstable emulsions with large drop sizes. An in vitro permeability study conducted using a Flow-Thru Dialyzer revealed that stable emulsions with drop sizes of 150-300 nm produce large and irreversible permeation of β-carotene to sheep intestine. On the other hand, unstable emulsions produced without the linker combination separated in the dialyzer chamber. Copyright © 2014 Elsevier B.V. All rights reserved.

Stimuli-sensitive hydrogels: ideal carriers for chronobiology and chronotherapy.

PubMed

Peppas, Nicholas A; Leobandung, William

2004-01-01

The development of solid-phase peptide synthesis in the early 1960s and recombinant DNA technology in the early 1970s boosted the scientific interest of utilizing proteins and peptides as potential therapeutic agents to battle poorly controlled diseases. While there has been rapid progress in the development and synthesis of new proteins and peptides as potential therapeutic agents, the formulation and development of the associated delivery systems is lacking. The development of delivery systems is equally important due to the problems of stability, low bioavailability and short half-life of proteins and peptides. The main problem in this field is that low stability leads to low bioavailability. In this review we draw attention to chrono-pharmacological drug-delivery systems, which can be used to match the delivery of therapeutic agents with the biological rhythm. They are very important especially in endocrinology and in vaccine therapy. We show that the treatment of hypopituitary dwarfism by administration of human growth-hormone-releasing hormone (GHRH) is more effective when GHRH is administered in a pulsatile manner that exhibits a period characteristic of the patient's circadian rhythm. Here we examine how to design novel chrono-pharmacological drug-delivery systems that should be able to release the therapeutic agents at predetermined intervals.

Portable system for temperature monitoring in all phases of wine production.

PubMed

Boquete, Luciano; Cambralla, Rafael; Rodríguez-Ascariz, J M; Miguel-Jiménez, J M; Cantos-Frontela, J J; Dongil, J

2010-07-01

This paper presents a low-cost and highly versatile temperature-monitoring system applicable to all phases of wine production, from grape cultivation through to delivery of bottled wine to the end customer. Monitoring is performed by a purpose-built electronic system comprising a digital memory that stores temperature data and a ZigBee communication system that transmits it to a Control Centre for processing and display. The system has been tested under laboratory conditions and in real-world operational applications. One of the system's advantages is that it can be applied to every phase of wine production. Moreover, with minimum modification, other variables of interest (pH, humidity, etc.) could also be monitored and the system could be applied to other similar sectors, such as olive-oil production. 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Measuring in vitro biotransformation rates of super hydrophobic chemicals in rat liver s9 fractions using thin-film sorbent-phase dosing.

PubMed

Lee, Yung-Shan; Otton, S Victoria; Campbell, David A; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2012-01-03

Methods for rapid and cost-effective assessment of the biotransformation potential of very hydrophobic and potentially bioaccumulative chemicals in mammals are urgently needed for the ongoing global evaluation of the environmental behavior of commercial chemicals. We developed and tested a novel solvent-free, thin-film sorbent-phase in vitro dosing system to measure the in vitro biotransformation rates of very hydrophobic chemicals in male Sprague-Dawley rat liver S9 homogenates and compared the rates to those measured by conventional solvent-delivery dosing. The thin-film sorbent-phase dosing system using ethylene vinyl acetate coated vials was developed to eliminate the incomplete dissolution of very hydrophobic substances in largely aqueous liver homogenates, to determine biotransformation rates at low substrate concentrations, to measure the unbound fraction of substrate in solution, and to simplify chemical analysis by avoiding the difficult extraction of test chemicals from complex biological matrices. Biotransformation rates using sorbent-phase dosing were 2-fold greater than those measured using solvent-delivery dosing. Unbound concentrations of very hydrophobic test chemicals were found to decline with increasing S9 and protein concentrations, causing measured biotransformation rates to be independent of S9 or protein concentrations. The results emphasize the importance of specifying both protein content and unbound substrate fraction in the measurement and reporting of in vitro biotransformation rates of very hydrophobic substances, which can be achieved in a thin-film sorbent-phase dosing system.

Nitric oxide-sensing actuators for modulating structure in lipid-based liquid crystalline drug delivery systems.

PubMed

Liu, Qingtao; Hu, Jinming; Whittaker, Michael R; Davis, Thomas P; Boyd, Ben J

2017-12-15

Herein we report on the development of a nitric oxide-sensing lipid-based liquid crystalline (LLC) system specifically designed to release encapsulated drugs on exposure to NO through a stimulated phase change. A series of nitric oxide (NO)-sensing lipids compatible with phytantriol and GMO cubic phases were designed and synthesized, and utilized in enabling nitric oxide-sensing LLC systems. The nitric oxide (NO)-sensing lipids react with nitric oxide, resulting in hydrolysis of these lipids and phase transition of the LLC system. Specifically, the N-3-aminopyridinyl myristylamine (NAPyM)+phytantriol mixture formed a lamellar phase in excess aqueous environment. The NAPyM+phytantriol LLC responded to the nitric oxide gas as a chemical stimulus which triggers a phase transition from lamellar phase to inverse cubic and hexagonal phase. The nitric oxide-triggered phase transition of the LLC accelerated the release of encapsulated model drug from the LLC bulk phase, resulting in a 15-fold increase in the diffusion coefficient compared to the starting lamellar structure. The nitric oxide-sensing LLC system has potential application in the development of smart medicines to treat nitric oxide implicated diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation

PubMed Central

Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Wu, Wei

2011-01-01

Background: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery. Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH. Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and α-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate. Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally. PMID:21822379

On the feasibility to conduct gradient liquid chromatography separations in narrow-bore columns at pressures up to 2000bar.

PubMed

De Pauw, Ruben; Swier, Tim; Degreef, Bart; Desmet, Gert; Broeckhoven, Ken

2016-11-18

The limits in operating pressures are extended for narrow-bore columns in gradient elution up to 2000bar. As the required pumps for these pressures are incompatible with common chromatographic solvents and are not suitable to apply a mobile phase composition gradient, a mobile phase delivery and injection system is described and experimentally validated which allows to use any possible chromatographic solvent in isocratic and gradient elution. The mobile phase delivery and injection system also allows to perform multiple separations without the need to depressurize the column. This system consists out of 5 dual on/off valves and two large volume loops in which the gradient and equilibration volume of initial mobile phase are loaded by a commercial liquid chromatography pump. The loops are then flushed toward the column at extreme pressures. The mobile phase delivery and injection system is first evaluated in isocratic elution and shows a comparable performance to a state-of-the-art commercial flow-through-needle injector but with twice the pressure rating. Distortion of the loaded gradient by dispersion in the gradient storage loop is studied. The effect of the most important parameters (such as flow rate, pressure and gradient steepness) is experimentally investigated. Different gradient steepnesses and volumes can be applied at different flow rates and operating pressures with a good repeatability. Due to the isobaric operation of the pumps, the gradient is monitored in real-time by a mass flow meter installed at the detector outlet. The chromatograms are then converted from time to volume-base. A separation of a 19-compound sample is performed on a 300×2.1mm column at 1000bar and on a 600×2.1mm column at 2000bar. The peak capacity was found to increase from 141 to 199 and thus scales with L as is predicted by theory. This allows to conclude that the inlet pressure for narrow-bore columns in gradient elution can be increased up to 2000bar without fundamental pressure-induced limitations. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison across Three Hybrid Lipid-Based Drug Delivery Systems for Improving the Oral Absorption of the Poorly Water-Soluble Weak Base Cinnarizine.

PubMed

Joyce, Paul; Yasmin, Rokhsana; Bhatt, Achal; Boyd, Ben J; Pham, Anna; Prestidge, Clive A

2017-11-06

Three state-of-the-art drug delivery vehicles engineered by nanostructuring lipid colloids within solid particle matrices were fabricated for the oral delivery of the poorly water-soluble, weak base, cinnarizine (CIN). The lipid and solid phase of each formulation was varied to systematically analyze the impact of key material characteristics, such as nanostructure and surface chemistry, on the in vitro and in vivo fate of CIN. The three systems formulated were: silica-stabilized lipid cubosomes (SSLC), silica-solid lipid hybrid (SSLH), and polymer-lipid hybrid (PLH) particles. Significant biopharmaceutical advantages were presented for CIN when solubilized in the polymer (poly(lactic-co-glycolic) acid; PLGA) and lipid phase of PLH particles compared to the lipid phases of SSLC and SSLH particles. In vitro dissolution in simulated intestinal conditions highlighted reduced precipitation of CIN when administered within PLH particles, given by a 4-5-fold improvement in the extent of CIN dissolution compared to the other delivery vehicles. Furthermore, CIN solubilization was enhanced 1.5-fold and 6-fold under simulated fasted state lipid digestion conditions when formulated with PLH particles compared to SSLH and SSLC particles, respectively. In vivo pharmacokinetics correlated well with in vitro solubilization data, whereby oral CIN bioavailability in rats, when encapsulated in the corresponding formulations, increased from SSLC < SSLH < PLH. The pharmacokinetic data obtained throughout this study indicated a synergistic effect between PLGA nanoparticles and lipid droplets in preventing CIN precipitation and thus, enhancing oral absorption. This synergy can be harnessed to efficiently deliver challenging poorly water-soluble, weak bases through oral administration.

Physical Factors Affecting Plasmid DNA Compaction in Stearylamine-Containing Nanoemulsions Intended for Gene Delivery

PubMed Central

Silva, André Leandro; Júnior, Francisco Alexandrino; Verissimo, Lourena Mafra; Agnez-Lima, Lucymara Fassarella; Egito, Lucila Carmem Monte; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Socrates Tabosa

2012-01-01

Cationic lipids have been used in the development of non-viral gene delivery systems as lipoplexes. Stearylamine, a cationic lipid that presents a primary amine group when in solution, is able to compact genetic material by electrostatic interactions. In dispersed systems such as nanoemulsions this lipid anchors on the oil/water interface confering a positive charge to them. The aim of this work was to evaluate factors that influence DNA compaction in cationic nanoemulsions containing stearylamine. The influence of the stearylamine incorporation phase (water or oil), time of complexation, and different incubation temperatures were studied. The complexation rate was assessed by electrophoresis migration on agarose gel 0.7%, and nanoemulsion and lipoplex characterization was done by Dynamic Light Scattering (DLS). The results demonstrate that the best DNA compaction process occurs after 120 min of complexation, at low temperature (4 ± 1 °C), and after incorporation of the cationic lipid into the aqueous phase. Although the zeta potential of lipoplexes was lower than the results found for basic nanoemulsions, the granulometry did not change. Moreover, it was demonstrated that lipoplexes are suitable vehicles for gene delivery. PMID:24281666

Mg2+-induced DNA compaction, condensation, and phase separation in gene delivery vehicles based on zwitterionic phospholipids: a dynamic light scattering and surface-enhanced Raman spectroscopic study.

PubMed

Süleymanoğlu, Erhan

2017-12-01

Despite the significant efforts towards applying improved non-destructive and label-free measurements of biomolecular structures of lipid-based gene delivery vectors, little is achieved in terms of their structural relevance in gene transfections. Better understanding of structure-activity relationships of lipid-DNA complexes and their gene expression efficiencies thus becomes an essential issue. Raman scattering offers a complimentary measurement technique for following the structural transitions of both DNA and lipid vesicles employed for their transfer. This work describes the use of SERS coupled with light scattering approaches for deciphering the bioelectrochemical phase formations between nucleic acids and lipid vesicles within lipoplexes and their surface parameters that could influence both the uptake of non-viral gene carriers and the endocytic routes of interacting cells. As promising non-viral alternatives of currently employed risky viral systems or highly cytotoxic cationic liposomes, complexations of both nucleic acids and zwitterionic lipids in the presence of Mg 2+ were studied applying colloidal Ag nanoparticles. It is shown that the results could be employed in further conformational characterizations of similar polyelectrolyte gene delivery systems.

Enhancement of oral bioavailability of atorvastatin calcium by self-emulsifying drug delivery systems (SEDDS).

PubMed

Kadu, Pawan J; Kushare, Sachin S; Thacker, Dhaval D; Gattani, Surendra G

2011-02-01

The aim of the present study was to formulate a self-emulsifying drug delivery system of atorvastatin calcium and its characterization including in vitro and in vivo potential. The solubility of atorvastatin calcium was determined in various vehicles such as Captex 355, Captex 355 EP/NF, Ethyl oleate, Capmul MCM, Capmul PG-8, Gelucire 44/14, Tween 80, Tween 20, and PEG 400. Pseudoternary phase diagrams were plotted on the basis of solubility data of drug in various components to evaluate the microemulsification region. Formulation development and screening was carried out based on results obtained from phase diagrams and characteristics of resultant microemulsion. Prepared formulations were tested for microemulsifying properties and evaluated for clarity, precipitation, viscosity determination, drug content and in vitro dissolution. The optimized formulation further evaluated for particle size distribution, zeta potential, stability studies and in vivo potential. In vivo performance of the optimized formulation was evaluated using a Triton-induced hypercholesterolemia model in male Albino Wistar rats. The formulation significantly reduced serum lipid levels as compared with atorvastatin calcium. Thus studies illustrated the potential use for the delivery of hydrophobic drug such as atorvastatin calcium by oral route.

Building a polysaccharide hydrogel capsule delivery system for control release of ibuprofen.

PubMed

Chen, Zhi; Wang, Ting; Yan, Qing

2018-02-01

Development of a delivery system which can effectively carry hydrophobic drugs and have pH response is becoming necessary. Here we demonstrate that through preparation of β-cyclodextrin polymer (β-CDP), a hydrophobic drug molecule of ibuprofen (IBU) was incorporated into our prepared β-CDP inner cavities, aiming to improve the poor water solubility of IBU. A core-shell capsule structure has been designed for achieving the drug pH targeted and sustained release. This delivery system was built with polysaccharide polymer of Sodium alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC) by physical cross-linking. The drug pH-response control release is this hydrogel system's chief merit, which has potential value for synthesizing enteric capsule. Besides, due to our simple preparing strategy, optimal conditions can be readily determined and the synthesis process can be accurately controlled, leading to consistent and reproducible hydrogel capsules. In addition, phase-solubility method was used to investigate the solubilization effect of IBU by β-CDP. SEM was used to prove the forming of core and shell structure. FT-IR and 1 H-NMR were also used to perform structural characteristics. By the technique of UV determination, the pH targeted and sustained release study were also performed. The results have proved that our prepared polysaccharide hydrogel capsule delivery system has potential applications as oral drugs delivery in the field of biomedical materials.

Reinforcement: Food Signals the Time and Location of Future Food

PubMed Central

Cowie, Sarah; Davison, Michael; Elliffe, Douglas

2011-01-01

It has long been understood that food deliveries may act as signals of future food location, and not only as strengtheners of prefood responding as the law of effect suggests. Recent research has taken this idea further—the main effect of food deliveries, or other “reinforcers”, may be signaling rather than strengthening. The present experiment investigated the ability of food deliveries to signal food contingencies across time after food. In Phase 1, the next food delivery was always equally likely to be arranged for a left- or a right-key response. Conditions were arranged such that the next food delivery was likely to occur either sooner on the left (or right) key, or sooner on the just-productive (or not-just-productive) key. In Phase 2, similar contingencies were arranged, but the last-food location was signaled by a red keylight. Preference, measured in 2-s bins across interfood intervals, was jointly controlled by the likely time and location of the next food delivery. In Phase 1, when any food delivery signaled a likely sooner next food delivery on a particular key, postfood preference was strongly toward that key, and moved toward the other key across the interreinforcer interval. In other conditions in which food delivery on the two keys signaled different subsequent contingencies, postfood preference was less extreme, and quickly moved toward indifference. In Phase 2, in all three conditions, initial preference was strongly toward the likely-sooner food key, and moved to the other key across the interfood interval. In both phases, at a more extended level of analysis, sequences of same-key food deliveries caused a small increase in preference for the just-productive key, suggesting the presence of a “reinforcement effect”, albeit one that was very small. PMID:21765546

Ultrasound-triggered drug delivery using acoustic droplet vaporization

NASA Astrophysics Data System (ADS)

Fabiilli, Mario Leonardo

The goal of targeted drug delivery is the spatial and temporal localization of a therapeutic agent and its associated bioeffects. One method of drug localization is acoustic droplet vaporization (ADV), whereby drug-laden perfluorocarbon (PFC) emulsions are vaporized into gas bubbles using ultrasound, thereby releasing drug locally. Transpulmonary droplets are converted into bubbles that occlude capillaries, sequestering the released drug within an organ or tumor. This research investigates the relationship between the ADV and inertial cavitation (IC) thresholds---relevant for drug delivery due to the bioffects generated by IC---and explores the delivery of lipophilic and hydrophilic compounds using PFC double emulsions. IC can positively and negatively affect ultrasound mediated drug delivery. The ADV and IC thresholds were determined for various bulk fluid, droplet, and acoustic parameters. At 3.5 MHz, the ADV threshold occurred at a lower rarefactional pressure than the IC threshold. The results suggest that ADV is a distinct phenomenon from IC, the ADV nucleus is internal to the droplet, and the IC nucleus is the bubble generated by ADV. The ADV triggered release of a lipophilic chemotherapeutic agent, chlorambucil (CHL), from a PFC-in-oil-in-water emulsion was explored using plated cells. Cells exposed to a CHL-loaded emulsion, without ADV, displayed 44% less growth inhibition than cells exposed to an equal concentration of CHL in solution. Upon ADV of the CHL-loaded emulsion, the growth inhibition increased to the same level as cells exposed to CHL in solution. A triblock copolymer was synthesized which enabled the formulation of stable water-in-PFC-in-water (W1/PFC/W2) emulsions. The encapsulation of fluorescein in the W1 phase significantly decreased the mass flux of fluorescein; ADV was shown to completely release the fluorescein from the emulsions. ADV was also shown to release thrombin, dissolved in the W1 phase, which could be used in vivo to extend synergistically the duration of ADV-generated, microbubble-based embolizations. Overall, the results suggest that PFC double emulsions can be used as an ultrasound-triggered drug delivery system. Compared to traditional drug delivery systems, ADV could be used to increase the therapeutic efficacy and decrease the systemic toxicity of drug therapy.

Delivery of Epinephrine in the Vapor Phase for the Treatment of Croup.

PubMed

Leung, Kitty; Newth, Christopher J L; Hotz, Justin C; O'Brien, Kevin C; Fink, James B; Coates, Allan L

2016-04-01

The Vapotherm system delivers high humidity to the airway of patients by using semipermeable tubules where heated liquid water is in contact with air. The humidified air is conducted to the patient via a heated tube. Preliminary clinical observations in infants with croup suggested that epinephrine added to the water supplying the humidity was delivered successfully in the vapor phase. The purpose of this study was to evaluate the efficiency of the delivery of epinephrine in the vapor phase and to develop the feasibility criteria for a clinical pilot study. Thirty milligrams of epinephrine in a 1-L bag of sterile water was used as the humidification source for a Vapotherm 2000i. The output of the heated circuit was condensed and collected into a small Erlenmeyer flask via a metal coil while the whole collection system was submerged in an ice slurry to maintain the outflow temperature from the flask between 0°C and 2°C. The in vitro system was tested at 40°C with flows of 5, 10, and 15 L/min and L-epinephrine concentrations of 15, 30, and 60 mg/L. Each test was duplicated at each of the six conditions. Academic children's hospital research laboratory. None. None. The system recovered more than 90% of the water vapor from the fully saturated air at 40°C. The epinephrine concentration recovery quantified by ultraviolet-visible spectrophotometry was 23.9% (27.5-20.4%) (mean and range) of the initial concentration. At flows of 5, 10, and 15 L/min, the delivery of epinephrine would be 1.8, 3.6, and 4.2 μg/min, respectively, which is in the therapeutic range used for parenteral infusion in young children. The Vapotherm system can be used to deliver epinephrine in pharmacological doses to the respiratory system as a vapor and thus as an alternative to droplets by conventional nebulization.

Hybrid films with phase-separated domains: A new class of functional materials

NASA Astrophysics Data System (ADS)

Kang, Minjee; Leal, Cecilia

The cell membrane is highly compartmentalized over micro-and nano scale. The compartmentalized domains play an important role in regulating the diffusion and distribution of species within and across the membrane. In this work, we introduced nanoscale heterogeneities into lipid films for the purpose of developing nature-mimicking phase-separated materials. The mixtures of phospholipids and amphiphilic block copolymers self-assemble into supported 1D multi-bilayers. We observed that in each lamella, mixtures of lipid and polymer phase-separate into domains that differ in their composition akin to sub-phases in cholesterol-containing lipid bilayers. Interestingly, we found evidence that like-domains are in registry across multilayers, making phase separation three-dimensional. To exploit such distinctive domain structure for surface-mediated drug delivery, we incorporated pharmaceutical molecules into the films. The drug release study revealed that the presence of domains in hybrid films modifies the diffusion pathways of drugs that become confined within phase-separated domains. A comprehensive domain structure coupled with drug diffusion pathways in films will be presented, offering new perspectives in designing a thin-film matrix system for controlled drug delivery. This work was supported by the National Science Foundation under Grant No. DMR-1554435.

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

[Breaking bad news in oncology: the Belgian experience].

PubMed

Delevallez, F; Lienard, A; Gibon, A-S; Razavi, D

2014-10-01

Breaking bad news is a complex and frequent clinical task for physicians working in oncology. It can have a negative impact on patients and their relatives who are often present during breaking bad news consultations. Many factors influence how the delivery of bad news will be experienced especially the communication skills used by physicians. A three-phase process (post-delivery phase, delivery phase, pre-delivery phase) has been developed to help physician to handle this task more effectively. Communication skills and specific breaking bad news training programs are both necessary and effective. A recent study conducted in Belgium has shown their impact on the time allocated to each of the three phases of this process, on the communication skills used, on the inclusion of the relative in the consultation and on physicians' physiological arousal. These results underscore the importance of promoting intensive communication skills and breaking bad news training programs for health care professionals.

Aerobrake concepts for NTP systems study

NASA Technical Reports Server (NTRS)

Cruz, Manuel I.

1992-01-01

Design concepts are described for landing large spacecraft masses on the Mars surface in support of manned missions with interplanetary transportation using Nuclear Thermal Propulsion (NTP). Included are the mission and systems analyses, trade studies and sensitivity analyses, design analyses, technology assessment, and derived requirements to support this concept. The mission phases include the Mars de-orbit, entry, terminal descent, and terminal touchdown. The study focuses primarily on Mars surface delivery from orbit after Mars orbit insertion using an NTP. The requirements associated with delivery of logistical supplies, habitats, and other equipment on minimum energy Earth to Mars transfers are also addressed in a preliminary fashion.

Drug delivery technologies for autoimmune disease.

PubMed

Phillips, Brett E; Giannoukakis, Nick

2010-11-01

Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome. Herein, the range of drug delivery methods available and under development and how they can be useful to treat autoimmune diseases are discussed. Polymer delivery methods, as well as biological methods that include fusion proteins, targeted antibodies, recombinant viruses and cell products are compared. Readers will gain insight into the progression of clinical trials for different technologies and drug delivery methods useful for targeting and modulating the function of autoreactive immune cells. Several tissue-specific polymer-based and biologic drug delivery systems are now in Phase II/III clinical trials. Although these trials are focused mainly on cancer treatment, lessons from these trials can guide the use of the same agents for autoimmunity therapeutics.

Inflatable Aeroponic System

NASA Technical Reports Server (NTRS)

Pelt, Jennifer Van

2005-01-01

Aeroponics Internationals (AI) innovation is a self-contained, self-supporting, flexible low mass aeroponic crop production unit with integral environmental systems for the control and delivery of a nutrient mist to the roots. This FLEX Aeroponic System model was developed for commercialization as a result of the NASA SBIR Phase I contract for the research and development of a low-mass, Inflatable Aeroponic System (IAS) for producing pesticide-free lettuces, grains, peppers, tomatoes and other vegetables. The innovation addresses the needs of water and nutrient delivery systems technologies for food production in space. The inflatable nature of the innovation makes it lightweight, allowing it to be deflated so it takes up less volume during transportation and storage. It improves upon AI's current aeroponic system design that uses more rigid structures and takes advantage of vertical inclines to increase bio-mass production by over 600%.

Reaching help on time in an emergency delivery.

PubMed

1991-01-01

Many maternal deaths in developing countries occur because mothers with complicated pregnancies or deliveries cannot be transported at all or fast enough to a health facility. A pregnant woman hemorrhaging greatly had to wait for a taxi because an unauthorized person had the health center's vehicle in Tanzania. Since most physicians practice in cities, most maternal deaths involve rural women. Further the less educated, lower the socioeconomic status, and lower the family's income the more likely she is to die. 3 phases contributed to transport delays of pregnant women. The 1st phase includes the time it take for a woman and her family to decide if her condition is serious enough to require medical attention, and if so, can they afford to pay for transport. Sometimes the services scare her or she considers the services to be of poor quality. The next phase involves the availability of transport and the distance between the mother and the services. Indeed in Nigeria, 96% of mothers who do not use medical delivery services report that they do not do so because of distance. Once at the health facility, the waiting period between arrival and meeting the woman's medical needs make up the 3rd phase. Often health facilities have inadequate number of medical personnel. Moreover the family must buy needed medical supplies before treatment can even begin. Alarm and transport systems are needed. In 1 area of India, pigeons carry messages to a physician that a woman is experiencing labor difficulties. Prior to the civil war in Somalia, a distinct flag informed passing motorists that emergency transport was needed for a pregnant woman who was carried to the roadside on a stretcher or in a cart. High technology transport is not cost effective and should not be part of a primary health care system.

Increasing the use of patient decision aids in orthopaedic care: results of a quality improvement project.

PubMed

Mangla, Mahima; Cha, Thomas D; Dorrwachter, Janet M; Freiberg, Andrew A; Leavitt, Lauren J; Rubash, Harry E; Simmons, Leigh H; Wendell, Emily L; Sepucha, Karen R

2018-05-01

To integrate patient decision aid (DA) delivery to promote shared decision-making and provide more patient-centred care within an orthopaedic surgery department for treatment of hip and knee osteoarthritis, lumbar herniated disc and lumbar spinal stenosis. Different strategies were used across three distinct phases to promote DA delivery. First, we used a quality improvement bonus to generate awareness and interest in the DAs among specialists. Second, we adapted the electronic referral management system to enable DA orders at referral to a specialist. Third, we engaged clinic staff and specialists to design workflows that promoted DA delivery. We tracked the number of patients who received a DA, who ordered the DA, and collected usage data from a subset of patients. Our target was to reach 60% of patients with DAs. In phase 1, 28% (43/155) of spine patients and 37% (114/308) of hip/knee patients received a DA. In phase 2, 54% (64/118) of spine referrals and 58% (189/324) of hip/knee referrals included a request to send a patient a DA. In phase 3, 56% (90/162) of spine patients and 69% (213/307) of hip/knee patients received a DA, significantly more than in phase 1 (P<0.0001). In phase 3, both more DAs were ordered by clinic staff compared with specialists (56% phase 3 vs 34% phase 1, P<0.001) and sent before the visit (74% phase 3 vs 17% phase 1, P<0.001). Patients were more likely to report reviewing the DA when delivered before the visit (63% before vs 50% after, P=0.005). DA implementation into clinic workflow is possible and facilitated by engagement of the entire care team and the support of health information technology. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Barriers to the Accessibility and Continuity of Health-Care Services in People with Multiple Sclerosis

PubMed Central

Bishop, Malachy; Pionke, J.J.; Strauser, David; Santens, Ryan L.

2017-01-01

Background: Individuals with multiple sclerosis (MS) face a range of barriers to accessing and using health-care services. The aim of this review was to identify specific barriers to accessing and using health-care services based on a continuum of the health-care delivery system. Methods: Literature searches were conducted in the PubMed, PsycINFO, CINAHL, and Web of Science databases. The following terms were searched as subject headings, key words, or abstracts: health care, access, barriers, physical disability, and multiple sclerosis. The literature search produced 361 potentially relevant citations. After screening titles, abstracts, and citations, eight citations were selected for full-text review. Results: Health-care barriers were divided into three continuous phases of receiving health care. In the before-visit phase, the most commonly identified barrier was transportation. In the during-visit phase, communication quality was the major concern. In the after-visit phase, discontinued referral was the major barrier encountered. Conclusions: There are multiple interrelated barriers to accessing and using health-care services along the health-care delivery continuum for people with MS and its associated physical disabilities, ranging from complex and long-recognized barriers that will likely require extended advocacy to create policy changes to issues that can and should be addressed through relatively minor changes in health-care delivery practices, improved care coordination, and increased provider awareness, education, and responsiveness to patients' needs. PMID:29270089

National Health Insurance and Health Education: Strategies for Change.

ERIC Educational Resources Information Center

Dwore, Richard B.

1980-01-01

The concept of National Health Insurance (NHI) as one of several strategies for resolving health problems in the U.S. is discussed. NHI goals include comprehensive health care, quality health care, efficient delivery systems, phased-in benefits, and consumer representation. (JD)

Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

NASA Astrophysics Data System (ADS)

Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

Planetary formation and water delivery in the habitable zone around solar-type stars in different dynamical environments

NASA Astrophysics Data System (ADS)

Zain, P. S.; de Elía, G. C.; Ronco, M. P.; Guilera, O. M.

2018-01-01

Context. Observational and theoretical studies suggest that there are many and various planetary systems in the Universe. Aims: We study the formation and water delivery of planets in the habitable zone (HZ) around solar-type stars. In particular, we study different dynamical environments that are defined by the most massive body in the system. Methods: First of all, a semi-analytical model was used to define the mass of the protoplanetary disks that produce each of the five dynamical scenarios of our research. Then, we made use of the same semi-analytical model to describe the evolution of embryos and planetesimals during the gaseous phase. Finally, we carried out N-body simulations of planetary accretion in order to analyze the formation and water delivery of planets in the HZ in the different dynamical environments. Results: Water worlds are efficiently formed in the HZ in different dynamical scenarios. In systems with a giant planet analog to Jupiter or Saturn around the snow line, super-Earths tend to migrate into the HZ from outside the snow line as a result of interactions with other embryos and accrete water only during the gaseous phase. In systems without giant planets, Earths and super-Earths with high water by mass contents can either be formed in situ in the HZ or migrate into it from outer regions, and water can be accreted during the gaseous phase and in collisions with water-rich embryos and planetesimals. Conclusions: The formation of planets in the HZ with very high water by mass contents seems to be a common process around Sun-like stars. Our research suggests that such planets are still very efficiently produced in different dynamical environments. Moreover, our study indicates that the formation of planets in the HZ with masses and water contents similar to those of Earth seems to be a rare process around solar-type stars in the systems under consideration.

Bioaccessibility of hydroxytyrosol and n-3 fatty acids as affected by the delivery system: simple, double and gelled double emulsions.

PubMed

Cofrades, Susana; Bou, Ricard; Flaiz, Linda; Garcimartín, Alba; Benedí, Juana; Mateos, Raquel; Sánchez-Muniz, Francisco J; Olivero-David, Raúl; Jiménez-Colmenero, Francisco

2017-06-01

This study examines the influence of different food-grade n-3 PUFA-enriched simple emulsion (SE), double emulsion (DE) and gelled double emulsion (GDE) delivery systems on the extent of lipolysis, antioxidant capacity and the bioaccessibility of hydroxytyrosol (HTy). GDE emulsion offered better protection for HTy (89%) than the other systems (79% in SE and DE). The reducing capacity of the emulsions containing HTy were not altered during oral digestion. However, "in vitro" gastric and intestinal phases significantly reduced the antioxidant activity of all systems. The structural and physical state of GDE entailed a slowing-down of triacylglyceride hydrolysis (36.4%) in comparison with that of SE and DE (22.7 and 24.8% for SE and DE, respectively).

A study on the gas-solid particle flows in a needle-free drug delivery device

NASA Astrophysics Data System (ADS)

Rasel, Md. Alim Iftekhar; Taher, Md. Abu; Kim, H. D.

2013-08-01

Different systems have been used over the years to deliver drug particles to the human skin for pharmaceutical effect. Research has been done to improve the performance and flexibility of these systems. In recent years a unique system called the transdermal drug delivery has been developed. Transdermal drug delivery opened a new door in the field of drug delivery as it is more flexible and offers better performance than the conventional systems. The principle of this system is to accelerate drug particles with a high speed gas flow. Among different transdermal drug delivery systems we will concentrate on the contour shock tube system in this paper. A contoured shock tube is consists of a rupture chamber, a shock tube and a supersonic nozzle section. The drug particles are retained between a set of bursting diaphragm. When the diaphragm is ruptured at a certain pressure, a high speed unsteady flow is initiated through the shock tube which accelerates the particles. Computational fluid dynamics is used to simulate and analyze the flow field. The DPM (discrete phase method) is used to model the particle flow. As an unsteady flow is initiated though the shock tube the drag correlation proposed by Igra et al is used other than the standard drag correlation. The particle velocities at different sections including the nozzle exit are investigated under different operating conditions. Static pressure histories in different sections in the shock tube are investigated to analyze the flow field. The important aspects of the gas and particle dynamics in the shock tube are discussed and analyzed in details.

Shuttle free-flying teleoperator system experiment definition. Volume 3: program development requirements

NASA Technical Reports Server (NTRS)

1972-01-01

The planning data are presented for subsequent phases of free-flying teleoperator program (FFTO) and includes costs, schedules and supporting research and technology activities required to implement the free-flying teleoperator system and associated flight equipment. The purpose of the data presented is to provide NASA with the information needed to continue development of the FFTO and integrate it into the space shuttle program. The planning data describes three major program phases consisting of activities and events scheduled to effect integrated design, development, fabrication and operation of an FFTO system. Phase A, Concept Generation, represents a study effort directed toward generating and evaluating a number of feasible FFTO experiment system concepts. Phase B, Definition, will include preliminary design and supporting analysis of the FFTO, the shuttle based equipment and ground support equipment. Phase C/D, Design, Development and Operations will include detail design of the operational FFTO, its integration into the space shuttle, hardware fabrication and testing, delivery of flight hardware and support of flight operations. Emphasis is placed on the planning for Phases A and B since these studies will be implemented early in the development cycle. Phase C/D planning is more general and subject to refinement during the definition phase.

Safe Active Scanning for Energy Delivery Systems Final Report

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

Helms, J.; Salazar, B.; Scheibel, P.

The Department of Energy’s Cybersecurity for Energy Delivery Systems Program has funded Safe(r) Active Scanning for Energy Delivery Systems, led by Lawrence Livermore National Laboratory, to investigate and analyze the impacts of active scanning in the operational environment of energy delivery systems. In collaboration with Pacific Northwest National Laboratory and Idaho National Laboratory, active scans across three testbeds including 38 devices were performed. This report gives a summary of the initial literature survey performed on the SASEDS project as well as industry partner interview summaries and main findings from Phase 1 of the project. Additionally, the report goes into themore » details of scanning techniques, methodologies for testing, testbed descriptions, and scanning results, with appendices to elaborate on the specific scans that were performed. As a result of testing, a single device out of 38 exhibited problems when actively scanned, and a reboot was required to fix it. This single failure indicates that active scanning is not likely to have a detrimental effect on the safety and resilience of energy delivery systems. We provide a path forward for future research that could enable wide adoption of active scanning and lead utilities to incorporate active scanning as part of their default network security plans to discover and rectify rogue devices, adversaries, and services that may be on the network. This increased network visibility will allow operational technology cybersecurity practitioners to improve their situational awareness of networks and their vulnerabilities.« less

Space shuttle phase B extension, volume 1

NASA Technical Reports Server (NTRS)

1971-01-01

In order to define a system which would significantly reduce payload delivery costs, activities were extended to modifications of the reusable space shuttle design concept. Considered were systems using orbiters with external propellant tanks and an interim expendable booster which allowed phased development of the usable orbiter and booster. Analyzed were: Merits of internal and external propellant tanks and the impact of external LH2 compared to L02 and LH2; impact of cargo bay size; impact abort; merit of expendable booster options; and merit of a phased development program. Studies showed that external L02/LH2 and the continued use of the J-2S engine on the orbiter reduced program cost and risk.

Innovating in health delivery: The Penn medicine innovation tournament.

PubMed

Terwiesch, Christian; Mehta, Shivan J; Volpp, Kevin G

2013-06-01

Innovation tournaments can drive engagement and value generation by shifting problem-solving towards the end user. In health care, where the frontline workers have the most intimate understanding of patients' experience and the delivery process, encouraging them to generate and develop new approaches is critical to improving health care delivery. In many health care organizations, senior managers and clinicians retain control of innovation. Frontline workers need to be engaged in the innovation process. Penn Medicine launched a system-wide innovation tournament with the goal of improving the patient experience. We set a quantitative goal of receiving 500 ideas and getting at least 1000 employees to participate in the tournament. A secondary goal was to involve various groups of the care process (doctors, nurses, clerical staff, transporters). The tournament was broken up into three phases. During Phase 1, employees were encouraged to submit ideas. Submissions were judged by an expert panel and crowd sourcing based on their potential to improve patient experience and ability to be implemented within 6 months. During Phase 2, the best 200 ideas were pitched during a series of 5 workshops and ten finalists were selected. During Phase 3, the best 10 ideas were presented to and judged by an audience of about 200 interested employees and a judging panel of 15 administrators. Two winners were selected. A total of 1739 ideas were submitted and over 5000 employees participated in the innovation tournament. Patient convenience/amenities (21%) was the top category of submission, with other popular areas including technology optimization (11%), assistance with navigation within UPHS (10%), and improving patient/family centered care (9%) and care delivery models/transitions (9%). A combination of winning and submitted ideas were implemented. Copyright © 2013 Elsevier Inc. All rights reserved.

Improved oral bioavailability of glyburide by a self-nanoemulsifying drug delivery system.

PubMed

Liu, Hongzhuo; Shang, Kuimao; Liu, Weina; Leng, Donglei; Li, Ran; Kong, Ying; Zhang, Tianhong

2014-01-01

The present study aimed at the development and characterisation of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble glyburide. The solubility of glyburide was determined in various oils, surfactants and co-surfactants which were grouped into two different combinations to construct ternary phase diagrams. The formulations were evaluated for emulsification time, droplet size, zeta-potential, electrical conductivity and stability of nanoemulsions. The optimised SNEDDS loading with 5 mg/g glyburide comprised 55% Cremophor® RH 40, 15% propanediol and 30% Miglyol® 812, which rapidly formed fine oil-in-water nanoemulsions with 46 ± 4 nm particle size. Compared with the commercial micronised tablets (Glynase®PresTab®), enhanced in vitro release profiles of SNEDDS were observed, resulting in the 1.5-fold increase of AUC following oral administration of SNEDDS in fasting beagle dogs. These results indicated that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of glyburide.

Stories and Music for Adolescent/Young Adult Resilience During Transplant Partnerships: Strategies to Support Academic-Clinical Nurse Collaborations in Behavioral Intervention Studies.

PubMed

Hendricks-Ferguson, Verna L; Barnes, Yvonne J; Cherven, Brooke; Stegenga, Kristin; Roll, Lona; Docherty, Sharon L; Haase, Joan E

Evidence-based nursing is in the forefront of healthcare delivery systems. Federal and state agencies, academic institutions, and healthcare delivery systems recognize the importance of nursing research. This article describes the mechanisms that facilitate nursing partnerships yielding high-level research outcomes in a clinical setting. A phase-II multicenter behavioral intervention study with pediatric stem cell transplant patients was the context of this academic/clinical research partnership. Strategies to develop and maintain this partnership involved a thorough understanding of each nurse's focus and barriers. A variety of communication plans and training events maximized preexisting professional networks. Academic/clinical nurses' discussions identified barriers to the research process, the most significant being role conflict. Communication and validation of benefits to each individual and institution facilitated the research process during challenging times. Establishing strong academic/clinical partnerships should lead to evidence-based research outcomes for the nursing profession, healthcare delivery systems, and patients and families.

System-Level Health-Care Integration and the Costs of Cancer Care Across the Disease Continuum.

PubMed

Kaye, Deborah R; Min, Hye Sung; Norton, Edward C; Ye, Zaojun; Li, Jonathan; Dupree, James M; Ellimoottil, Chad; Miller, David C; Herrel, Lindsey A

2018-03-01

Policy reforms in the Affordable Care Act encourage health care integration to improve quality and lower costs. We examined the association between system-level integration and longitudinal costs of cancer care. We used linked SEER-Medicare data to identify patients age 66 to 99 years diagnosed with prostate, bladder, esophageal, pancreatic, lung, liver, kidney, colorectal, breast, or ovarian cancer from 2007 to 2012. We attributed each patient to one or more phases of care (ie, initial, continuing, and end of life) according to time from diagnosis until death or end of study interval. For each phase, we aggregated all claims with the primary cancer diagnosis and identified patients treated in an integrated delivery network (IDN), as defined by the Becker Hospital Review list of the top 100 most integrated health delivery systems. We then determined if care provided in an IDN was associated with decreased payments across cancers and for each individual cancer by phase and across phases. We identified 428,300 patients diagnosed with one of 10 common cancers. Overall, there were no differences in phase-based payments between IDNs and non-IDNs. Average adjusted annual payments by phase for IDN versus non-IDNs were as follows: initial, $14,194 versus $14,421, respectively ( P = .672); continuing, $2,051 versus $2,099 ( P = .566); and end of life, $16,257 versus $16,232 ( P = .948). However, in select cancers, we observed lower payments in IDNs. For bladder cancer, payments at the end of life were lower for IDNs ($11,041 v $12,331; P = .008). Of the four cancers with the lowest 5-year survival rates (ie, pancreatic, lung, esophageal, and liver), average expenditures during the initial and continuing-care phases were lower for patients with liver cancer treated in IDNs. For patients with one of 10 common malignancies, treatment in an IDN generally is not associated with lower costs during any phase of cancer care.

Collagen and hyaluronic acid hydrogel in water-in-oil microemulsion delivery systems.

PubMed

Kupper, Sylwia; Kłosowska-Chomiczewska, Ilona; Szumała, Patrycja

2017-11-01

The increase in skin related health issues has promoted interest in research on the efficacy of microemulsion in dermal and transdermal delivery of active ingredients. Here, we assessed the water-in-oil microemulsion capacity to incorporate two natural polymers, i.e. collagen and hyaluronic acid with low and high molecular weight. Systems were extensively characterized in terms of conductivity, phase inversion studies, droplet diameter, polydispersity index and rheological properties. The results of this research indicate that the structure and extent of water phase in microemulsions is governed by ratio and amount of surfactant mixture (sorbitan ester derivatives). However, results have also shown that collagen, depending upon the weight of the molecule and its surface activity, influence the droplet size of the microemulsions. While the hyaluronic acid, especially with high molecular weight, due to the water-binding ability and hydrogel formation alters the rheological properties of the microemulsion, thus providing viscous consistency of the formulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel microemulsion-based gels for topical delivery of indomethacin: Formulation, physicochemical properties and in vitro drug release studies.

PubMed

Froelich, Anna; Osmałek, Tomasz; Snela, Agnieszka; Kunstman, Paweł; Jadach, Barbara; Olejniczak, Marta; Roszak, Grzegorz; Białas, Wojciech

2017-12-01

Microemulsion-based semisolid systems may be considered as an interesting alternative to the traditional dosage forms applied in topical drug delivery. Mechanical properties of topical products are important both in terms of application and dosage form effectiveness. In this study we designed and evaluated novel microemulsion-based gels with indomethacin and analyzed the factors affecting their mechanical characteristics and drug release. The impact of the microemulsion composition on the extent of isotropic region was investigated with the use of pseudoternary phase diagrams. Selected microemulsions were analyzed in terms of electrical conductivity and surface tension in order to determine the microemulsion type. Microemulsions were transformed into polymer-based gels and subjected to rheological and textural studies. Finally, the indomethacin release from the analyzed gels was studied and compared to commercially available product. The extent of isotropic domain in pseudoternary phase diagrams seems to be dependent on the polarity of the oil phase. The surface tension and conductivity monitored as a function of water content in microemulsion systems revealed possible structural transformations from w/o through bicontinuous systems into o/w. The mechanical properties of semisolid microemulsion-based systems depended on the composition of surface active agents and the drug presence. The drug release profiles observed in the case of the investigated gels differed from those recorded for the commercially available product which was most probably caused by the different structure of both systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Thermodynamics of Indomethacin Adsorption to Phospholipid Membranes.

PubMed

Fearon, Amanda D; Stokes, Grace Y

2017-11-22

Using second-harmonic generation, we directly monitored adsorption of indomethacin, a nonsteroidal anti-inflammatory drug, to supported lipid bilayers composed of phospholipids of varying phase, cholesterol content, and head group charge without the use of extrinsic labels at therapeutically relevant aqueous concentrations. Indomethacin adsorbed to gel-phase lipids with a high binding affinity, suggesting that like other arylacetic acid-containing drugs, it preferentially interacts with ordered lipid domains. We discovered that adsorption of indomethacin to gel-phase phospholipids was endothermic and entropically driven, whereas adsorption to fluid-phase phospholipids was exothermic and enthalpically driven. As temperature increased from 19 to 34 °C, binding affinities to gel-phase lipids increased by 7-fold but relative surface concentration decreased to one-fifth of the original value. We also compared our results to the entropies reported for indomethacin adsorbed to surfactant micelles, which are used in drug delivery systems, and assert that adsorbed water molecules in the phospholipid bilayer may be buried deeper into the acyl chains and less accessible for disruption. The thermodynamic studies reported here provide mechanistic insight into indomethacin interactions with mammalian plasma membranes in the gastrointestinal tract and inform studies of drug delivery, where indomethacin is commonly used as a prototypical, hydrophobic small-molecule drug.

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.

Improving drug delivery technology for treating neurodegenerative diseases.

PubMed

Choonara, Yahya E; Kumar, Pradeep; Modi, Girish; Pillay, Viness

2016-07-01

Neurodegenerative diseases (NDs) represent intricate challenges for efficient uptake and transport of drugs to the brain mainly due to the restrictive blood-brain barrier (BBB). NDs are characterized by the loss of neuronal subtypes as sporadic and/or familial and several mechanisms of neurodegeneration have been identified. This review attempts to recap, organize and concisely evaluate the advanced drug delivery systems designed for treating common NDs. It highlights key research gaps and opinionates on new neurotherapies to overcome the BBB as an addition to the current treatments of countering oxidative stress, inflammation and apoptotic mechanisms. Current treatments do not fully address the biological, drug and therapeutic factors faced. This has led to the development of vogue treatments such as nose-to-brain technologies, bio-engineered systems, fusion protein chaperones, stem cells, gene therapy, use of natural compounds, neuroprotectants and even vaccines. However, failure of these treatments is mainly due to the BBB and non-specific delivery in the brain. In order to increase neuroavailability various advanced drug delivery systems provide promising alternatives that are able to augment the treatment of Alzheimer's disease and Parkinson's disease. However, much work is still required in this field beyond the preclinical testing phase.

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

Thyrotropin-Releasing Hormone Loaded and Chitosan Engineered Polymeric Nanoparticles: Towards Effective Delivery of Neuropeptides.

PubMed

Kaur, Sarabjit; Bhararia, Avani; Sharma, Krishna; Mittal, Sherry; Jain, Rahul; Wangoo, Nishima; Sharma, Rohit K

2016-05-01

Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L-pGlu-L-His-L- Pro-NH2, is used in the treatment of brain/spinal injury and certain central nervous system (CNS) disorders, including schizophrenia, Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound effects on the CNS. However, TRH's therapeutic activity is severely hampered because of instability and hydrophilicity owing to its peptidic nature which results into ineffective penetration into the blood brain barrier. In the present study, we report the synthesis and stability studies of novel chitosan engineered TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim of such an encapsulation is to allow effective delivery of TRH in biological systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out manually in solution phase followed by its encapsulation using PLGA to form polymeric nanoparticles (NPs) via nanoprecipitation technique. Different parameters such as type of organic phase, concentration of stabilizer, ratio of organic phase and aqueous phase, rate of addition of organic phase were optimized, tested and evaluated for particle size, encapsulation efficiency, and stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to achieve positive surface charge rendering them potential membrane penetrating agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom Electron Microscopy (TEM) and Infra-red spectroscopic techniques.

Characterization of caprylocaproyl macrogolglycerides based microemulsion drug delivery vehicles for an amphiphilic drug.

PubMed

Djordjevic, Ljiljana; Primorac, Marija; Stupar, Mirjana; Krajisnik, Danina

2004-03-01

Microemulsion systems composed of water, isopropyl myristate, PEG-8 caprylic/capric glycerides (Labrasol), and polyglyceryl-6 dioleate (Plurol Oleique), were investigated as potential drug delivery vehicles for an amphiphilic model drug (diclofenac diethylamine). Pseudo-ternary phase diagram of the investigated system, at constant surfactant/cosurfactant mass ratio (Km 4:1) was constructed at room temperature by titration, and the oil-to-surfactant/cosurfactant mass ratios (O/SC) that exhibit the maximum in the solubilization of water were found. This allowed the investigation of the continuous structural inversion from water-in-oil to oil-in-water microemulsions on dilution with water phase. Furthermore, electrical conductivity (sigma) of the system at Km 1:4, and O/SC 0.250 was studied, and the percolation phenomenon was observed. Conductivity and apparent viscosity (eta') measurement results well described colloidal microstructure of the selected formulations, including gradual changes during their formation. Moreover, sigma, eta', and pH values of six selected microemulsion vehicles which differ in water phase volume fraction (phi(w)) at the selected Km and O/SC values, were measured. In order to investigate the influence of the amphiphilic drug on the vehicle microstructures, each system was formulated with 1.16% (w/w) diclofenac diethylamine. Electrical conductivity, and eta' of the investigated systems were strongly affected by drug incorporation. The obtained results suggest that diclofenac diethylamine interacts with the specific microstructure of the investigated vehicles, and that the different drug release kinetics from these microemulsions may be expected. The investigated microemulsions should be very interesting as new drug carrier systems for dermal application of diclofenac diethylamine.

The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model.

PubMed

Cherniakov, Irina; Izgelov, Dvora; Domb, Abraham J; Hoffman, Amnon

2017-11-15

The lipophilic phytocannabinoids cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) show therapeutic efficacy in various medical conditions. Both molecules are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%. We have developed an advanced lipid based Self-Emulsifying Drug Delivery System termed Advanced Pro-NanoLiposphere (PNL) pre-concentrate. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds. Advanced PNLs are PNLs with an incorporated natural absorption enhancers. These molecules are natural alkaloids and phenolic compounds which were reported to inhibit certain phase I and phase II metabolism processes. Here we use piperine, curcumin and resveratrol to formulate the Advanced-PNL formulations. Consequently, we have explored the utility of these Advanced-PNLs on CBD and THC oral bioavailability. Oral administration of CBD-piperine-PNL resulted in 6-fold increase in AUC compared to CBD solution, proving to be the most effective of the screened formulations. The same trend was found in pharmacokinetic experiments of THC-piperine-PNL which resulted in a 9.3-fold increase in AUC as compared to THC solution. Our Piperine-PNL can be used as a platform for synchronized delivery of piperine and CBD or THC to the enterocyte site. This co-localization provides an increase in CBD and THC bioavailability by its effect at the pre-enterocyte and the enterocyte levels of the absorption process. The extra augmentation in the absorption of CBD and THC by incorporating piperine into PNL is attributed to the inhibition of Phase I and phase II metabolism by piperine in addition to the Phase I metabolism and P-gp inhibition by PNL. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized compounds that currently cannot be administered orally. Copyright © 2017. Published by Elsevier B.V.

Emerging therapies for Parkinson's disease.

PubMed

Poewe, Werner; Mahlknecht, Philipp; Jankovic, Joseph

2012-08-01

The experimental therapeutics of Parkinson's disease are reviewed, highlighting the current pipeline of emerging therapeutic approaches. This review includes novel approaches to dopaminergic drug delivery such as intraintestinal infusions or new extended-release formulations of levodopa and also intrapulmonary delivery of apomorphine as well as novel dopaminergic agents like the monoamine oxidase-B inhibitor safinamide or novel catechol-O-methyl transferase inhibitors. An even greater number of ongoing clinical trials assess the efficacy and safety of nondopaminergic approaches to enhance motor control or reduce motor complications like fluctuations and dyskinesias. These include adenosine A2A antagonists, α-adrenergic and serotonergic agonists as well as drugs acting on the glutamatergic system. Gene-based or cell-based intrastriatal delivery of therapeutic principles that enhance striatal dopaminergic transmission directly or via the stimulation of trophic activity has also reached phase II clinical development with encouraging results in some studies. Finally, a wide spectrum of agents with a potential for slowing disease progression is currently tested. A variety of medical and nonmedical interventions in different phases of clinical development provide an interesting and promising portfolio of emerging therapies for Parkinson's disease.

Dynamically accumulated dose and 4D accumulated dose for moving tumors

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

Li Heng; Li Yupeng; Zhang Xiaodong

2012-12-15

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove themore » principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and/or total deliver time was also established.« less

Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.

PubMed

Boonme, Prapaporn; Kaewbanjong, Jarika; Amnuaikit, Thanaporn; Andreani, Tatiana; Silva, Amélia M; Souto, Eliana B

2016-01-01

Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals.

Pieter Cullis' quest for a lipid-based, fusogenic delivery system for nucleic acid therapeutics: success with siRNA so what about mRNA?

PubMed

Tam, Ying K; Madden, Thomas D; Hope, Michael J

2016-11-01

For the best part of 40 years, lipids and membrane fusion have been at the center of Pieter's research. Projects range from the purely academic quest of understanding the roles of lipids in biological membranes, to the translation of this knowledge into the most advanced lipid nanoparticle (LNP) drug delivery systems in clinical trials to-date. Pieter's pioneering work in lipid polymorphism and characterizing the unique properties of unsaturated phospatidyethanolamines (PE), together with the introduction of ionizable, dialkylamino lipids to trigger membrane fusion at acidic pH, provided the foundation on which a new generation of highly potent, well-tolerated LNPs for intravenous delivery of nucleic acid therapeutics has been built. In this contribution to the special edition honoring Pieter's achievements we highlight key research conducted in Pieter's laboratory and at several biotechnology companies, some spun out of his research group, which resulted in the development of a fusogenic delivery system for siRNA therapeutics. Patisiran®, an LNP encapsulating siRNA for hepatic gene silencing, is currently in Phase III clinical trials for treatment of Transthyretin amyloidosis as are several other siRNA products employing this delivery technology. Finally, we describe more recent work in which the platform shows real promise in the rapidly growing new field of mRNA therapeutics.

Conceptual and Preliminary Design of a Low-Cost Precision Aerial Delivery System

DTIC Science & Technology

2016-06-01

test results. It includes an analysis of the failure modes encountered during flight experimentation , methodology used for conducting coordinate...and experimentation . Additionally, the current and desired end state of the research is addressed. Finally, this chapter outlines the methodology ...preliminary design phases are utilized to investigate and develop a potentially low-cost alternative to existing systems. Using an Agile methodology

Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption

PubMed Central

Zeng, Ni; Gao, Xiaoling; Hu, Quanyin; Song, Qingxiang; Xia, Huimin; Liu, Zhongyang; Gu, Guangzhi; Jiang, Mengyin; Pang, Zhiqing; Chen, Hongzhuan; Chen, Jun; Fang, Liang

2012-01-01

Background Lipid-based liquid crystalline nanoparticles (LCNPs) have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized. Methods In this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a “ ball-like”/“hexagonal” morphology. Results Cellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and to fuse with the cell membrane. An in vivo pharmacokinetic study showed that the oral bioavailability of paclitaxel-loaded LCNPs (13.16%) was 2.1 times that of Taxol® (the commercial formulation of paclitaxel, 6.39%). Conclusion The findings of this study suggest that this LCNP delivery system may be a promising candidate for improving the oral bioavailability of poorly water-soluble agents. PMID:22888230

Evaluating Innovations in Home Care for Performance Accountability.

PubMed

Collister, Barbara; Gutscher, Abram; Ambrogiano, Jana

2016-01-01

Concerns about rising costs and the sustainability of our healthcare system have led to a drive for innovative solutions and accountability for performance. Integrated Home Care, Calgary Zone, Alberta Health Services went beyond traditional accountability measures to use evaluation methodology to measure the progress of complex innovations to its organization structure and service delivery model. This paper focuses on the first two phases of a three-phase evaluation. The results of the first two phases generated learning about innovation adoption and sustainability, and performance accountability at the program-level of a large publicly funded healthcare organization.

Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

PubMed Central

Zhang, Youwen; Tong, Deyin; Che, Daobiao; Pei, Bing; Xia, Xiaodong; Yuan, Gaofeng; Jin, Xin

2017-01-01

The roles of ginsenoside compound K (CK) in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP)/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS) mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 μg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects. PMID:28144142

Delivering Coordinated Cancer Care by Building Transactive Memory in a Team of Teams.

PubMed

Henry, Elizabeth; Silva, Abigail; Tarlov, Elizabeth; Czerlanis, Cheryl; Bernard, Margie; Chauhan, Cynthia; Schalk, Denise; Stewart, Greg

2016-11-01

Cancer care delivery is highly complex. Treatment involves coordination within oncology health-care teams and across other teams of referring primary and specialty providers (a team of teams). Each team interfaces with patients and caregivers to offer component parts of comprehensive care. Because patients frequently obtain specialty care from divergent health-care systems resulting in cross-system health-care use, oncology teams need mechanisms to coordinate and collaborate within and across health-care systems to optimize clinical outcomes for all cancer patients. Transactive memory is one potential strategy that can help improve comprehensive patient care delivery. Transactive memory is a process by which two or more team professionals develop a shared system for encoding, storing, and retrieving information. Each professional is responsible for retaining only part of the total information. Applying this concept to a team of teams results in system benefits wherein all teams share an understanding of specialized knowledge held by each component team. The patient's role as the unifying member of the team of teams is central to successful treatment delivery. This clinical case presents a patient who is receiving oral treatment for advanced prostate cancer within two health systems. The case emphasizes the potential for error when multiple teams function without a point team (the team coordinating efforts of all other primary and specialty teams) and when the specialty knowledge of providers and patients is not well integrated into all phases of the care delivery process.

Oral Vaccination Against Anthrax Using a Transgenic Plant Expressing Protective Antigen.

DTIC Science & Technology

1996-09-01

unpublished results). In Phase II, development of a tomato -based system for edible vaccine delivery will be carried out in parallel with experiments testing...Frederick, MD 21702-5012. AUTHORITY USAMRMC ltr, 4 Dec 2002 THIS PAGE IS UNCLASSIFIED AD CONTRACT NUMBER: DAMD17-95-C-5102 TITLE: Oral Vaccination ...COVERED I September 1996 Final - Phase I, 15 Auxg 95-14 Aug 96 4. TITLE AND 9UBTITLE 5. FUNDING NUMBERS Oral Vaccination Against Anthrax Using a Transgenic

Combustor oscillation attenuation via the control of fuel-supply line dynamics

DOEpatents

Richards, George A.; Gemmen, Randall S.

1998-01-01

Combustion oscillation control in combustion systems using hydrocarbon fuels is provided by acoustically tuning a fuel-delivery line to a desired phase of the combustion oscillations for providing a pulse of a fuel-rich region at the oscillating flame front at each time when the oscillation produced pressure in the combustion chamber is in a low pressure phase. The additional heat release produced by burning such fuel-rich regions during low combustion chamber pressure effectively attenuates the combustion oscillations to a selected value.

Predicting protein instability in sustained protein delivery systems using spectral-phase interference.

PubMed

Seidel, Nina; Sitterberg, Johannes; Vornholt, Wolfgang; Bakowsky, Udo; Keusgen, Michael; Kissel, Thomas

2012-02-01

Biodegradable and non-biodegradable polymers represent promising materials for sustained protein delivery systems. However, structural protein instabilities due to interactions with the polymer surface are often observed. Aim of the present study was to analyze and predict these instabilities by determination of adsorption pattern and extent via biomolecular interaction analysis. A new optical method based on spectral-phase interference successfully demonstrated its suitability for this new application scope. It was characterized in terms of sensitivity, reproducibility and dynamic range using bovine serum albumin (BSA) as model compound. For protein-polymer interaction studies, materials with different wettabilities and zeta potential were selected and successfully applied on the sensor chip: Glass, poly(styrene), poly(lactic acid), poly(lactic-co-glycolic acid), and poly(ethylene carbonate). Concentration dependent adsorption curves revealed two principal adsorption patterns based on the connection between BSA spreading and supply rate. This connection was stronger influenced by polymer hydrophobicity than surface charge. Association, dissociation and binding rate constants in the range from 0.15 to 34.19 × 10(-6) M were obtained. Atomic force microscopy images of the films before and after adsorption confirmed the previous elaborated model. Poly(ethylene carbonate) emerged as highly promising biomaterial for protein delivery due to its favorable adsorption behavior based on low polymer-protein interactions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

PubMed

Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

2013-12-28

Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

Time-reversal Techniques in Ultrasound-assisted Convection-enhanced Drug Delivery to the Brain: Technology Development and In Vivo Evaluation

PubMed Central

Lewis, George K.; Guarino, Sabrina; Gandhi, Gaurav; Filinger, Laurent; Lewis, George K.; Olbricht, Willam L.; Sarvazyan, Armen

2011-01-01

We describe a drug delivery method that combines Time-Reversal Acoustics (TRA) with Convection-Enhanced Delivery (CED) to improve the delivery of therapeutics to the interstitium of the brain. The Ultrasound-assisted CED approach (UCED) circumvents the blood-brain barrier by infusing compounds through a cannula that is inserted into the brain while simultaneously delivering ultrasound to improve the penetration of pharmaceuticals. CED without ultrasound-assistance has been used to treat a variety of neural disorders, including glioblastoma multiforme, a malignancy that presents a very poor prognosis for patients. We describe a novel system that is used to infuse fluids into the brain parenchyma while simultaneously exposing the tissue to safe levels of 1-MHz, low intensity, ultrasound energy. The system includes a combined infusion needle-hydrophone, a 10-channel ultralow-output impedance amplifier, a broad-band ultrasound resonator, and MatLab®-based TRA control and user-interface. TRA allows easy coupling of ultrasound therapy through the skull without complex phase-correction and array design. The smart targeting UCED system has been tested in vivo and results show it provides 1.5-mm spatial resolution for UCED and improves tracer distribution in the brain over CED alone. PMID:21881622

Green fluorescent protein (GFP): is seeing believing and is that enough?

PubMed

Shorter, Susan A; Pettit, Marie W; Dyer, Paul D R; Coakley Youngs, Emma; Gorringe-Pattrick, Monique A M; El-Daher, Samer; Richardson, Simon

Intracellular compartmentalisation is a significant barrier to the successful nucleocytosolic delivery of biologics. The endocytic system has been shown to be responsible for compartmentalisation, providing an entry point, and trigger(s) for the activation of drug delivery systems. Consequently, many of the technologies used to understand endocytosis have found utility within the field of drug delivery. The use of fluorescent proteins as markers denoting compartmentalisation within the endocytic system has become commonplace. Several of the limitations associated with the use of green fluorescent protein (GFP) within the context of drug delivery have been explored here by asking a series of related questions: (1) Are molecules that regulate fusion to a specific compartment (i.e. Rab- or SNARE-GFP fusions) a good choice of marker for that compartment? (2) How reliable was GFP-marker overexpression when used to define a given endocytic compartment? (3) Can glutathione-s-transferase (GST) fused in frame with GFP (GST-GFP) act as a fluid phase endocytic probe? (4) Was GFP fluorescence a robust indicator of (GFP) protein integrity? This study concluded that there are many appropriate and useful applications for GFP; however, thought and an understanding of the biological and physicochemical character of these markers are required for the generation of meaningful data.

The Apollo experiment for document delivery via satellite communication

NASA Astrophysics Data System (ADS)

1985-03-01

Dutch participation possibilities in the Apollo document delivery project, wishes and idea's of potential user and tender groups, and plans and activities of Dutch institutes and companies, are surveyed. The Apollo storage and transport system, demand and administration network, potential markets, and subject areas of the documents are investigated. Utilization areas (scientific, technical, administration, and business information) are listed. High tariffs and the lack of necessary provision make a direct participation strategy impossible. However, in the experimental phase, Dutch companies must be allowed to contribute in technical developments and availability of organizational and technical facilities must be stimulated.

PLGA based drug delivery systems: Promising carriers for wound healing activity.

PubMed

Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

2016-03-01

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.

Solar cell power for field instrumentation at White Sands Missile range. Final report

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

Bond, J.W. Jr..; Reckart, D.H. Jr; Milway, W.B.

1978-01-01

The initial phase of an Instrumentation Development Project to explore and document what solar power can do for remote field instrumentation systems is described. The work scope consisted of selection, design, construction, test, and delivery of a solar cell power system for White Sands Missile Range. A Drone Formation Control System Interrogator was selected; a power supply was built and installed in the San Andres Mountain Range at WSMR in late August 1977.

A nanoparticulate drug-delivery system for rivastigmine: physico-chemical and in vitro biological characterization.

PubMed

Craparo, Emanuela Fabiola; Pitarresi, Giovanna; Bondì, Maria Luisa; Casaletto, Maria Pia; Licciardi, Mariano; Giammona, Gaetano

2008-03-10

The preparation and characterization of surface-PEGylated polymeric nanoparticles are described. These systems were obtained by UV irradiation of PHM and PHM-PEG(2000) as an inverse microemulsion, using an aqueous solution of the PHM/PHM-PEG(2000) copolymer mixture as the internal phase and triacetin saturated with water as the external phase, and characterized by dimensional analysis, zeta-potential measurements and XPS. in vitro biological tests demonstrated their cell compatibility and their ability to escape from phagocytosis. Rivastigmine was encapsulated into the nanoparticle structure and drug-release profiles from loaded samples were investigated in PBS at pH = 7.4 and human plasma.

Formation of highly structured cubic micellar lipid nanoparticles of soy phosphatidylcholine and glycerol dioleate and their degradation by triacylglycerol lipase.

PubMed

Wadsäter, Maria; Barauskas, Justas; Nylander, Tommy; Tiberg, Fredrik

2014-05-28

Lipid nanoparticles of reversed internal phase structures, such as cubic micellar (I2) structure show good drug loading ability of peptides and proteins as well as some small molecules. Due to their controllable small size and inner morphology, such nanoparticles are suitable for drug delivery using several different administration routes, including intravenous, intramuscular, and subcutaneous injection. A very interesting system in this regard, is the two component soy phosphatidylcholine (SPC)/glycerol dioleate (GDO) system, which depending on the ratio of the lipid components form a range of reversed liquid crystalline phases. For a 50/50 (w/w) ratio in excess water, these lipids have been shown to form a reversed cubic micellar (I2) phase of the Fd3m structure. Here, we demonstrate that this SPC/GDO phase, in the presence of small quantities (5-10 wt %) of Polysorbate 80 (P80), can be dispersed into nanoparticles, still with well-defined Fd3m structure. The resulting nanoparticle dispersion has a narrow size distribution and exhibit good long-term stability. In pharmaceutical applications, biodegradation pathways of the drug delivery vehicles and their components are important considerations. In the second part of the study we show how the structure of the particles evolves during exposure to a triacylglycerol lipase (TGL) under physiological-like temperature and pH. TGL catalyzes the lipolytic degradation of acylglycerides, such as GDO, to monoglycerides, glycerol, and free fatty acids. During the degradation, the interior phase of the particles is shown to undergo continuous phase transitions from the reversed I2 structure to structures of less negative curvature (2D hexagonal, bicontinuous cubic, and sponge), ultimately resulting in the formation of multilamellar vesicles.

COLLABORATIVE RESEARCH AND DEVELOPMENT (CR&D) Delivery Order 0067: Molecular Simulations for Hydrated Polymer Fuel Membranes

DTIC Science & Technology

2007-11-01

proton transfer. 1. INTRODUCTION While polymer electrolyte membrane fuel cells ( PEMFCs ) hold out the possibility for providing several important...Among the broader aims of the research is to develop PEMFC systems which can operate at higher temperatures than presently achievable while still...efforts have provided insight into the mechanisms which enable proton conduction in PEMFCs . Hydrated membranes are two-phase systems, an

Microemulsions containing lecithin and sugar-based surfactants: nanoparticle templates for delivery of proteins and peptides.

PubMed

Graf, Anja; Ablinger, Elisabeth; Peters, Silvia; Zimmer, Andreas; Hook, Sarah; Rades, Thomas

2008-02-28

Two pseudo-ternary systems comprising isopropyl myristate, soybean lecithin, water, ethanol and either decyl glucoside (DG) or capryl-caprylyl glucoside (CCG) as surfactant were investigated for their potential to form microemulsion templates to produce nanoparticles as drug delivery vehicles for proteins and peptides. All microemulsion and nanoparticle compounds used were pharmaceutically acceptable and biocompatible. Phase diagrams were established and characterized using polarizing light microscopy, viscosity, conductivity, electron microscopy, differential scanning calorimetry and self-diffusion NMR. An area in the phase diagrams containing optically isotropic, monophasic systems was designated as the microemulsion region and systems therein identified as solution-type microemulsions. Poly(alkylcyanoacrylate) nanoparticles prepared by interfacial polymerisation from selected microemulsions ranged from 145 to 660nm in size with a unimodal size distribution depending on the type of monomer (ethyl (2) or butyl (2) cyanoacrylate) and microemulsion template. Generally larger nanoparticles were formed by butyl (2) cyanoacrylate. Insulin was added as a model protein and did not alter the physicochemical behaviour of the microemulsions or the morphology of the nanoparticles. However, insulin-loaded nanoparticles in the CCG containing system decreased in size when using butyl (2) cyanoacrylate. This study shows that microemulsions containing sugar-based surfactants are suitable formulation templates for the formation of nanoparticles to deliver peptides.

Design of microemulsion system suitable for the oral delivery of poorly aqueous soluble beta-carotene.

PubMed

Peng, Cheng; Svirskis, Darren; Lee, Sung Je; Oey, Indrawati; Kwak, Hae-Soo; Chen, Guanyu; Bunt, Craig; Wen, Jingyuan

2017-02-14

Beta-carotene is a potent antioxidant for maintaining human health. However, its oral absorption is low due to poor aqueous solubility of less than 1 μg/ml. A microemulsion delivery system was designed to solubilize beta-carotene toward enhancing its oral bioavailability. From seven pseudoternary diagrams constructed, three systems were selected with large microemulsion areas suitable for oral administration and dilution in the predominately aqueous gastrointestinal fluids. Conductivity and rheology characterization were conducted along four dilution lines within the selected systems. Three pseudoternary-phase diagrams were selected with large microemulsion regions, >60% of the total phase diagram area, which provide microemulsions with higher drug-loading capacity. A phenomenon was observed by which both propylene glycol and Capmul MCM EP stabilize the microstructure of the microemulsions has been proposed based on the characterization studies. An optimal bicontinuous microemulsion formulation was selected comprising 12% orange oil, 24% Capmul MCM, 18% Tween 20, 6% Labrasol, 20% propylene glycol and 20% water, with a high beta-carotene loading capacity of 140.8 μg/ml and droplet size of 117.4 nm. In conclusion, the developed novel microemulsion formulation allows solubilizing beta-carotene and is a promising basis for further development as a functional beverage.

Clinical implementation of target tracking by breathing synchronized delivery

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

Tewatia, Dinesh; Zhang Tiezhi; Tome, Wolfgang

2006-11-15

Target-tracking techniques can be categorized based on the mechanism of the feedback loop. In real time tracking, breathing-delivery phase correlation is provided to the treatment delivery hardware. Clinical implementation of target tracking in real time requires major hardware modifications. In breathing synchronized delivery (BSD), the patient is guided to breathe in accordance with target motion derived from four-dimensional computed tomography (4D-CT). Violations of mechanical limitations of hardware are to be avoided at the treatment planning stage. Hardware modifications are not required. In this article, using sliding window IMRT delivery as an example, we have described step-by-step the implementation of targetmore » tracking by the BSD technique: (1) A breathing guide is developed from patient's normal breathing pattern. The patient tries to reproduce this guiding cycle by following the display in the goggles; (2) 4D-CT scans are acquired at all the phases of the breathing cycle; (3) The average tumor trajectory is obtained by deformable image registration of 4D-CT datasets and is smoothed by Fourier filtering; (4) Conventional IMRT planning is performed using the images at reference phase (full exhalation phase) and a leaf sequence based on optimized fluence map is generated; (5) Assuming the patient breathes with a reproducible breathing pattern and the machine maintains a constant dose rate, the treatment process is correlated with the breathing phase; (6) The instantaneous average tumor displacement is overlaid on the dMLC position at corresponding phase; and (7) DMLC leaf speed and acceleration are evaluated to ensure treatment delivery. A custom-built mobile phantom driven by a computer-controlled stepper motor was used in the dosimetry verification. A stepper motor was programmed such that the phantom moved according to the linear component of tumor motion used in BSD treatment planning. A conventional plan was delivered on the phantom with and without motion. The BSD plan was also delivered on the phantom that moved with the prescheduled pattern and synchronized with the delivery of each beam. Film dosimetry showed underdose and overdose in the superior and inferior regions of the target, respectively, if the tumor motion is not compensated during the delivery. BSD delivery resulted in a dose distribution very similar to the planned treatments.« less

Drug delivery properties of macroporous polystyrene solid foams.

PubMed

Canal, Cristina; Aparicio, Rosa Maria; Vilchez, Alejandro; Esquena, Jordi; García-Celma, Maria José

2012-01-01

Polymeric porous foams have been evaluated as possible new pharmaceutical dosage forms. These materials were obtained by polymerization in the continuous phase of highly concentrated emulsions prepared by the phase inversion temperature method. Their porosity, specific surface and surface topography were characterized, and the incorporation and release of active principles was studied using ketoprofen as model lipophilic molecule. Solid foams with very high pore volume, mainly inside macropores, were obtained by this method. The pore morphology of the materials was characterized, and very rough topography was observed, which contributed to their nearly superhydrophobic properties. These solid foams could be used as delivery systems for active principles with pharmaceutical interest, and in the present work ketoprofen was used as a model lipophilic molecule. Drug incorporation and release was studied from solid foam disks, using different concentrations of the loading solutions, achieving a delayed release with short lag-time.

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

PubMed Central

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

2016-01-01

An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release. PMID:27876876

Liquid-liquid two phase systems for the production of porous hydrogels and hydrogel microspheres for biomedical applications: A tutorial review

PubMed Central

Elbert, Donald L.

2010-01-01

Macroporous hydrogels may have direct applications in regenerative medicine as scaffolds to support tissue formation. Hydrogel microspheres may be used as drug delivery vehicles or as building blocks to assemble modular scaffolds. A variety of techniques exist to produce macroporous hydrogels and hydrogel microspheres. A subset of these relies on liquid-liquid two phase systems. Within this subset, vastly different types of polymerization processes are found. In this review, the history, terminology and classification of liquid-liquid two phase polymerization and crosslinking are described. Instructive examples of hydrogel microsphere and macroporous scaffold formation by precipitation/dispersion, emulsion and suspension polymerizations are used to illustrate the nature of these processes. The role of the kinetics of phase separation in determining the morphology of scaffolds and microspheres is also delineated. Brief descriptions of miniemulsion, microemulsion polymerization and ionotropic gelation are also included. PMID:20659596

Interleukin-2: Old and New Approaches to Enhance Immune-Therapeutic Efficacy.

PubMed

Dhupkar, Pooja; Gordon, Nancy

2017-01-01

Interleukin-2 (IL-2) is a very well-known cytokine that has been studied for the past 35 years. It plays a major role in the growth and proliferation of many immune cells such NK and T cells. It is an important immunotherapy cytokine for the treatment of various diseases including cancer. Systemic delivery of IL-2 has shown clinical benefit in renal cell carcinoma and melanoma patients. However, its use has been limited by the numerous toxicities encountered with the systemic delivery. Intravenous IL-2 causes the well-known "capillary leak syndrome," or the leakage of fluid from the circulatory system to the interstitial space resulting in hypotension (low blood pressure), edema, and dyspnea that can lead to circulatory shock and eventually cardiopulmonary collapse and multiple organ failure. Due to the toxicities associated with systemic IL-2, an aerosolized delivery approach has been developed, which enables localized delivery and a higher local immune cell activation. Since proteins are absorbed via pulmonary lymphatics, after aerosol deposition in the lung, aerosol delivery provides a means to more specifically target IL-2 to the local immune system in the lungs with less systemic effects. Its benefits have extended to diseases other than cancer. Delivery of IL-2 via aerosol or as nebulized IL-2 liposomes has been previously shown to have less toxicity and higher efficacy against sarcoma lung metastases. Dogs with cancer provided a highly relevant means to determine biodistribution of aerosolized IL-2 and IL-2 liposomes. However, efficacy of single-agent IL-2 is limited. As in general, for most immune-therapies, its effect is more beneficial in the face of minimal residual disease. To overcome this limitation, combination therapies using aerosol IL-2 with adoptive transfer of T cells or NK cells have emerged.Using a human osteosarcoma (OS) mouse model, we have demonstrated the efficacy of single-agent aerosol IL-2 and combination therapy aerosol IL-2 and NK cells or aerosol IL-2 and interleukin 11 receptor alpha-directed chimeric antigen receptor-T cells (IL-11 receptor α CAR-T cells) against OS pulmonary metastases. Combination therapy resulted in a better therapeutic effect. A Phase-I trial of aerosol IL-2 was done in Europe and proved to be safe. Others and our preclinical studies provided the basis for the development of a Phase-I aerosol IL-2 trial in our institution to include younger patients with lung metastases. OS, our disease of interest, has a peak incidence in the adolescent and young adult years. Our goal is to complete this trial in the next 2 years.In this chapter, we summarize the different effects of IL-2 and cover the advantages of the aerosol delivery route for diseases of the lung with an emphasis on some of our most recent work using combination therapy aerosol IL-2 and NK cells for the treatment of OS lung metastases.

Paclitaxel loaded phospholipid-based gel as a drug delivery system for local treatment of glioma.

PubMed

Chen, Tijia; Gong, Ting; Zhao, Ting; Liu, Xing; Fu, Yao; Zhang, Zhirong; Gong, Tao

2017-08-07

Paclitaxel (PTX) is a chemotherapeutic agent and has been widely used in clinic against human cancer. However, it has limited application in brain tumor treatment due to the poor penetration of blood brain barrier. Local delivery system is a promising carrier of PTX in the treatment of glioma. A biodegradable phospholipid-based gel (PG) system was developed for intratumoral injection and evaluated in brain glioma-bearing mice model. PTX loaded PG was composed of phospholipid, ethanol, medium chain triglyceride, triacetin and PTX. It was prepared by a very simple method. The system was a transparent solution with good fluidity, while turned into a gel after phase-transition when ethanol diffused. Both in vitro dissolution and in vivo imaging study proved the sustained release effect of PG system. In vivo tolerability study showed a better tolerability after mice treated with PTX PG compared with free PTX. The survival time of brain glioma-bearing mice after treatment with PTX PG was significantly prolonged compared with mice treated by free PTX (P<0.05). In conclusion, this study developed a novel PG based local PTX delivery system with simple preparation method, good tolerability and high therapeutic efficacy. It has a great potential to improve the clinical management of glioma. Copyright © 2017 Elsevier B.V. All rights reserved.

Systemically administered gp100 encoding DNA vaccine for melanoma using water-in-oil-in-water multiple emulsion delivery systems.

PubMed

Kalariya, Mayurkumar; Amiji, Mansoor M

2013-09-10

The purpose of this study was to develop a water-in-oil-in-water (W/O/W) multiple emulsions-based vaccine delivery system for plasmid DNA encoding the gp100 peptide antigen for melanoma immunotherapy. The gp100 encoding plasmid DNA was encapsulated in the inner-most aqueous phase of squalane oil containing W/O/W multiple emulsions using a two-step emulsification method. In vitro transfection ability of the encapsulated plasmid DNA was investigated in murine dendritic cells by transgene expression analysis using fluorescence microscopy and ELISA methods. Prophylactic immunization using the W/O/W multiple emulsions encapsulated the gp100 encoding plasmid DNA vaccine significantly reduced tumor volume in C57BL/6 mice during subsequent B16-F10 tumor challenge. In addition, serum Th1 cytokine levels and immuno-histochemistry of excised tumor tissues indicated activation of cytotoxic T-lymphocytes mediated anti-tumor immunity causing tumor growth suppression. The W/O/W multiple emulsions-based vaccine delivery system efficiently delivers the gp100 plasmid DNA to induce cell-mediated anti-tumor immunity. Copyright © 2013 Elsevier B.V. All rights reserved.

Population Health Management for Inflammatory Bowel Disease.

PubMed

Dulai, Parambir S; Singh, Siddharth; Ohno-Machado, Lucilla; Sandborn, William J

2018-01-01

Inflammatory bowel diseases (IBDs) are chronic and impose significant, multidimensional burdens on patients and health care systems. The increasing prevalence of IBD will only worsen this problem globally-population health management (PHM) strategies are needed to increase quality of care and population health outcomes while reducing health care costs. We discuss the key components of PHM in IBD. Effective implementation of PHM strategies requires accurate identification of at-risk patients and key areas of variability in care. Improving outcomes of the at-risk population requires implementation of a multicomponent chronic care model designed to shift delivery of ambulatory care from acute, episodic, and reactive encounters, to proactive, planned, long-term care. This is achieved through team care of an activated patient with the help of remote monitoring, clinical information systems, and integrated decision support, with accompanying changes in delivery systems. Performance measurement is integral to any PHM strategy. This involves developing and implementing meaningful metrics of different phases of quality of IBD care and measuring them efficiently using modern clinical information systems. Such an integrated framework of PHM in IBD will facilitate the delivery of high-value care to patients. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio

PubMed Central

Lai, Jui-Yang

2013-01-01

Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations. PMID:24187486

Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio.

PubMed

Lai, Jui-Yang

2013-01-01

Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations.

Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery

NASA Astrophysics Data System (ADS)

Wang, Xiaoyong; Zhou, Zijian; Wang, Zhiyong; Xue, Yunxin; Zeng, Yun; Gao, Jinhao; Zhu, Lei; Zhang, Xianzhong; Liu, Gang; Chen, Xiaoyuan

2013-08-01

This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability.This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02797j

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

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

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi

2012-09-15

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase weremore » extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When {+-}20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. Conclusions: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.« less

Magnetic water-in-water droplet microfluidics

NASA Astrophysics Data System (ADS)

Navi, Maryam; Abbasi, Niki; Tsai, Scott

2017-11-01

Aqueous two-phase systems (ATPS) have shown to be ideal candidates for replacing the conventional water-oil systems used in droplet microfluidics. We use an ATPS of Polyethylene Glycol (PEG) and Dextran (DEX) for microfluidic generation of magnetic water-in-water droplets. As ferrofluid partitions to DEX phase, there is no significant diffusion of ferrofluid at the interface of the droplets, rendering generation of magnetic DEX droplets in a non-magnetic continuous phase of PEG possible. In this system, both phases are water-based and highly biocompatible. We microfluidically generate magnetic DEX droplets at a flow-focusing junction in a jetting regime. We sort the droplets based on their size by placing a permanent magnet downstream of the droplet generation region, and show that the deflection of droplets is in good agreement with a mathematical model. We also show that the magnetic DEX droplets can be stabilized by lysozyme and be used for separation of single cell containing water-in-water droplets. This system of magnetic water-in-water droplet manipulation may find biomedical applications such as single-cell studies and drug delivery.

Intranasal delivery of antiviral siRNA.

PubMed

Barik, Sailen

2011-01-01

Intranasal administration of synthetic siRNA is an effective modality of RNAi delivery for the prevention and therapy of respiratory diseases, including pulmonary infections. Vehicles used for nasal siRNA delivery include established as well as novel reagents, many of which have been recently optimized. In general, they all promote significant uptake of siRNA into the lower respiratory tract, including the lung. When properly designed and optimized, these siRNAs offer significant protection against respiratory viruses such as influenza virus, parainfluenza virus and respiratory syncytial virus (RSV). Nasally administered siRNA remains within the lung and does not access systemic blood flow, as judged by its absence in other major organs such as liver, heart, kidney, and skeletal muscle. Adverse immune reaction is generally not encountered, especially when immunogenic and/or off-target siRNA sequences and toxic vehicles are avoided. In fact, siRNA against RSV has entered Phase II clinical trials in human with promising results. Here, we provide a standardized procedure for using the nose as a specific route for siRNA delivery into the lung of laboratory animals. It should be clear that this simple and efficient system has enormous potential for therapeutics.

An Initiative to Reduce the Episiotomy Rate: Association of Feedback and the Hawthorne Effect With Leapfrog Goals.

PubMed

Zhang-Rutledge, Kathy; Clark, Steven L; Denning, Stacie; Timmins, Audra; Dildy, Gary A; Gandhi, Manisha

2017-07-01

To assess the association of education, performance feedback, and the Hawthorne effect with a reduction in the episiotomy rate in a large academic institution. We describe a prospective observational study of a project conducted between March 2012 and February 2017 to assist clinicians in meeting the Leapfrog Group (www.leapfroggroup.org) target rates for episiotomy. Phases of this project included preintervention (phase 1, March 2012 to April 2014), education and provision of collective department episiotomy rates (phase 2, May 2014 to December 2014), ongoing education with emphasis on a revised Leapfrog target rate (phase 3, January 2015 to February 2016), and provision of individual episiotomy rates to practitioners on a monthly basis (phase 4, March 2016 to February 2017). We analyzed the department episiotomy rates before, during, and after these efforts. Cases of shoulder dystocia were excluded from this analysis. Statistical analysis was performed using a two-tailed Student t test and χ test with P<.05 considered significant. During the study period 1,176 episiotomies were performed in 16,441 vaginal deliveries (7.2%). In phase 2 (2,352 vaginal deliveries), there was a nonsignificant drop in the episiotomy rate with education alone (9.0-8.2%, P=.21). In phase 3 (4,379 vaginal deliveries), the episiotomy rate demonstrated an additional, significant drop to 5.9% (P<.001), but this reduction did not reach the new Leapfrog goal of 5%. In phase 4 (3,160 vaginal deliveries), the hospital episiotomy rate again dropped significantly from 5.9% to 4.37% (P=.007) and met the target rate of 5%. This reduction was sustained over a 12-month time period. During this same time period, the rate of operative vaginal delivery among vaginal births increased (4.5-5.4%, P=.003) and there was no significant change in the rates of third- and fourth-degree perineal laceration (3.8-3.3%, P=.19). Education, performance feedback, and the Hawthorne effect were associated with a reduction in the episiotomy rate in a large academic institution without a reduction in the rate of operative vaginal delivery or an increase in the rate of third- and fourth-degree lacerations.

Self-nanoemulsifying drug delivery systems of tamoxifen citrate: design and optimization.

PubMed

Elnaggar, Yosra S R; El-Massik, Magda A; Abdallah, Ossama Y

2009-10-01

Tamoxifen citrate is an antiestrogen for peroral breast cancer treatment. The drug delivery encounters problems of poor water solubility and vulnerability to enzymatic degradation in both intestine and liver. In the current study, tamoxifen citrate self-nanoemulsifying drug delivery systems (SNEDDS) were prepared in an attempt to circumvent such obstacles. Preliminary screening was carried out to select proper ingredient combinations. All surfactants screened were recognized for their bioactive aspects. Ternary phase diagrams were then constructed and an optimum system was designated. Three tamoxifen SNEDDS were then compared for optimization. The systems were assessed for robustness to dilution, globule size, cloud point, surface morphology and drug release. An optimum system composed of tamoxifen citrate (1.6%), Maisine 35-1 (16.4%), Caproyl 90 (32.8%), Cremophor RH40 (32.8%) and propylene glycol (16.4%) was selected. The system was robust to different dilution volumes and types. It possessed a mean globule size of 150 nm and a cloud point of 80 degrees C. Transmission electron microscopy demonstrated spherical particle morphology. The drug release from the selected formulation was significantly higher than other SNEDDS and drug suspension, as well. Realizing drug incorporation into an optimized nano-sized SNEDD system that encompasses a bioactive surfactant, our results proposed that the prepared system could be promising to improve oral efficacy of the tamoxifen citrate.

Effect of Prime Contractor Financial Position on Major Weapon System Cost and Delivery Performance

DTIC Science & Technology

1990-12-01

financial healh , before before and during both development and production phases of a program. Major findings indicate that a relationship does exist...curves were constructed for 35 major military aircraft and missile weapon systems to operationalize the concept of pricing strategy. [Ref. 4:p. 14]. To...Meaningfulness of coefficients, i.e., predictors must have "correct" coefficient signs. The following discriminarit model resulted: Concept Ratio

Alternatives generation and analysis for double-shell tank primary ventilation systems emissions control and monitoring

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

SEDERBURG, J.P.

1999-09-30

This AGA addresses the question: ''What equipment upgrades, operational changes, and/or other actions are required relative to the DST tanks farms' ventilation systems to support retrieval, staging (including feed sampling), and delivery of tank waste to the Phase I private contractor?'' Issues and options for the various components within the ventilation subsystem affect each other. Recommended design requirements are presented and the preferred alternatives are detailed.

Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

PubMed

Babaei, S; Ghanbarzadeh, S; Adib, Z M; Kouhsoltani, M; Davaran, S; Hamishehkar, H

2016-05-01

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

Analysis of phase conjugation in a turbid medium

NASA Astrophysics Data System (ADS)

Hollmann, Joseph L.; Cantero, Sergio; Tseng, Snow; DiMarzio, Charles A.

2014-03-01

The ability to focus light in most tissue degrades quickly with depth due to high optical scattering. Recently, researchers have found they can concentrate light tightly despite these scattering effects by using a guidestar and optical phase conjugation to focus light to greater distances in tissue. An optical or probe signal is transmitted through a scattering medium and its resulting wavefront is detected. The wavefront is then conjugated and utilized as a new optical source or delivery wave that focuses back to the guidestar's location with minimal scattering. The power in the delivery wave may be greatly increased for enhanced energy delivery at the focus. Modulation by an ultrasound (US) beam may be utilized to generate the guidestar dynamically and allow for US-resolution at depths of several millimeters. The delivery wave is successful at focusing light back at the guidestar because it creates constructive interference at the desired focus. However, if the phases of the field contributions change, we expect the delivered power at the focus to be reduced. This paper will analyze the robustness of this method when the probe beam is at one wavelength and the delivery wave is at another. This will allow us to characterize the deleterious effects of varying the phase contributions at the focus.

Amorphous Calcium Carbonate Based-Microparticles for Peptide Pulmonary Delivery.

PubMed

Tewes, Frederic; Gobbo, Oliviero L; Ehrhardt, Carsten; Healy, Anne Marie

2016-01-20

Amorphous calcium carbonate (ACC) is known to interact with proteins, for example, in biogenic ACC, to form stable amorphous phases. The control of amorphous/crystalline and inorganic/organic ratios in inhalable calcium carbonate microparticles may enable particle properties to be adapted to suit the requirements of dry powders for pulmonary delivery by oral inhalation. For example, an amorphous phase can immobilize and stabilize polypeptides in their native structure and amorphous and crystalline phases have different mechanical properties. Therefore, inhalable composite microparticles made of inorganic (i.e., calcium carbonate and calcium formate) and organic (i.e., hyaluronan (HA)) amorphous and crystalline phases were investigated for peptide and protein pulmonary aerosol delivery. The crystalline/amorphous ratio and polymorphic form of the inorganic component was altered by changing the microparticle drying rate and by changing the ammonium carbonate and HA initial concentration. The bioactivity of the model peptide, salmon calcitonin (sCT), coprocessed with alpha-1-antitrypsin (AAT), a model protein with peptidase inhibitor activity, was maintained during processing and the microparticles had excellent aerodynamic properties, making them suitable for pulmonary aerosol delivery. The bioavailability of sCT after aerosol delivery as sCT and AAT-loaded composite microparticles to rats was 4-times higher than that of sCT solution.

Benchmarking Course Completion Rates: A Method with an Example from the British Columbia Open University

ERIC Educational Resources Information Center

Giguere, Louis

2007-01-01

We report findings on the methodological phase of a research project designed to assess the progress of the British Columbia Open University (BCOU) toward a 1997 goal of increasing distance education course completion rates to British Columbia system levels by adapting existing "off-line" courses for online delivery (a virtualization…

Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

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

J Torin Huzil; S Sivaloganathan; M Kohandel

The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein andmore » nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.« less

Combustor oscillation attenuation via the control of fuel-supply line dynamics

DOEpatents

Richards, G.A.; Gemmen, R.S.

1998-09-22

Combustion oscillation control in combustion systems using hydrocarbon fuels is provided by acoustically tuning a fuel-delivery line to a desired phase of the combustion oscillations for providing a pulse of a fuel-rich region at the oscillating flame front at each time when the oscillation produced pressure in the combustion chamber is in a low pressure phase. The additional heat release produced by burning such fuel-rich regions during low combustion chamber pressure effectively attenuates the combustion oscillations to a selected value. 9 figs.

Design, characterization, and biological evaluation of curcumin-loaded surfactant-based systems for topical drug delivery.

PubMed

Fonseca-Santos, Bruno; Dos Santos, Aline Martins; Rodero, Camila Fernanda; Gremião, Maria Palmira Daflon; Chorilli, Marlus

From previous studies, it has been found that curcumin exhibits an anti-inflammatory activity and is being used for the treatment of skin disorders; however, it is hydrophobic and has weak penetrating ability, resulting in poor drug transport through the stratum corneum. The aim of this study was to develop liquid crystalline systems for topical administration of curcumin for the treatment of inflammation. These liquid crystalline systems were developed from oleic acid, polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol, and water as the surfactant, oil phase, and aqueous phase, respectively. These systems were characterized, and polarized light microscopy showed anisotropy with lamellar mesophases (Formulation 1) and hexagonal mesophases (Formulations 2 and 3), which were confirmed by the peak ratio measured using small-angle X-ray scattering. In addition, rheological tests revealed that the formulations exhibited gel-like behavior (G'>G″), as evidenced by the increased G' values that indicate structured systems. Texture profile analysis showed that hexagonal mesophases have high values of hardness, adhesiveness, and compressibility, which indicate structured systems. In vitro studies on bioadhesion revealed that the hexagonal mesophases increased the bioadhesiveness of the systems to the skin of the pig ear. An in vivo inflammation experiment showed that the curcumin-loaded hexagonal mesophase exhibited an anti-inflammatory activity as compared to the positive control (dexamethasone). The results suggest that this system has a potential to be used as a bioadhesive vehicle for the topical administration of curcumin. Therefore, it is possible to conclude that these systems can be used for the optimization of drug delivery systems to the skin.

SU-E-T-56: A Novel Approach to Computing Expected Value and Variance of Point Dose From Non-Gated Radiotherapy Delivery

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

Zhou, S; Zhu, X; Zhang, M

Purpose: Randomness in patient internal organ motion phase at the beginning of non-gated radiotherapy delivery may introduce uncertainty to dose received by the patient. Concerns of this dose deviation from the planned one has motivated many researchers to study this phenomenon although unified theoretical framework for computing it is still missing. This study was conducted to develop such framework for analyzing the effect. Methods: Two reasonable assumptions were made: a) patient internal organ motion is stationary and periodic; b) no special arrangement is made to start a non -gated radiotherapy delivery at any specific phase of patient internal organ motion.more » A statistical ensemble was formed consisting of patient’s non-gated radiotherapy deliveries at all equally possible initial organ motion phases. To characterize the patient received dose, statistical ensemble average method is employed to derive formulae for two variables: expected value and variance of dose received by a patient internal point from a non-gated radiotherapy delivery. Fourier Series was utilized to facilitate our analysis. Results: According to our formulae, the two variables can be computed from non-gated radiotherapy generated dose rate time sequences at the point’s corresponding locations on fixed phase 3D CT images sampled evenly in time over one patient internal organ motion period. The expected value of point dose is simply the average of the doses to the point’s corresponding locations on the fixed phase CT images. The variance can be determined by time integration in terms of Fourier Series coefficients of the dose rate time sequences on the same fixed phase 3D CT images. Conclusion: Given a non-gated radiotherapy delivery plan and patient’s 4D CT study, our novel approach can predict the expected value and variance of patient radiation dose. We expect it to play a significant role in determining both quality and robustness of patient non-gated radiotherapy plan.« less

Linear feature extraction from radar imagery: SBIR (Small Business Innovative Research), phase 2, option 2

NASA Astrophysics Data System (ADS)

Milgram, David L.; Kahn, Philip; Conner, Gary D.; Lawton, Daryl T.

1988-12-01

The goal of this effort is to develop and demonstrate prototype processing capabilities for a knowledge-based system to automatically extract and analyze features from Synthetic Aperture Radar (SAR) imagery. This effort constitutes Phase 2 funding through the Defense Small Business Innovative Research (SBIR) Program. Previous work examined the feasibility of and technology issues involved in the development of an automated linear feature extraction system. This final report documents this examination and the technologies involved in automating this image understanding task. In particular, it reports on a major software delivery containing an image processing algorithmic base, a perceptual structures manipulation package, a preliminary hypothesis management framework and an enhanced user interface.

Differential scanning calorimetry: An invaluable tool for a detailed thermodynamic characterization of macromolecules and their interactions

PubMed Central

Chiu, Michael H.; Prenner, Elmar J.

2011-01-01

Differential Scanning Calorimetry (DSC) is a highly sensitive technique to study the thermotropic properties of many different biological macromolecules and extracts. Since its early development, DSC has been applied to the pharmaceutical field with excipient studies and DNA drugs. In recent times, more attention has been applied to lipid-based drug delivery systems and drug interactions with biomimetic membranes. Highly reproducible phase transitions have been used to determine values, such as, the type of binding interaction, purity, stability, and release from a drug delivery mechanism. This review focuses on the use of DSC for biochemical and pharmaceutical applications. PMID:21430954

Bleomycin--electrical pulse delivery: electroporation therapy-bleomycin--Genetronics; MedPulser-bleomycin--Genetronics.

PubMed

2004-01-01

Genetronics Biomedical is using its electroporation therapy technology to deliver bleomycin to tumour cells for the treatment of cancer. Genetronics have developed the MedPulser Electroporation Therapy System, which consists of an electrical pulse generator and disposable electrode applicators. The MedPulser system enables the delivery of large molecules into cells by briefly applying an electric field to the cell. This causes a transient permeability in the cell's outer membrane characterised by the appearance of pores across the membrane. After the field is discontinued, the pores close, trapping the therapeutic molecules inside the target cells. Genetronics is using the MedPulser System in conjunction with bleomycin, an antineoplastic antibiotic that binds to DNA causing strand scissions. Genetronics is seeking a licensing partner for the use of electroporation for the delivery of drugs in chemotherapy. In 1998, Genetronics entered a licensing and development agreement with Ethicon for electroporation and electrofusion. Under the terms of this agreement, Ethicon was to develop and clinically test the Genetronics electroporation delivery system and conduct all regulatory activities throughout the world except Canada. Ethicon would also market the products once regulatory approval has been obtained and Genetronics was to receive a percentage of the net sales and as license fees. However, in July 2000, Ethicon exercised its rights to terminate the agreement without cause. All rights were returned to Genetronics in January 2001. In 1997, Genetronics entered an agreement with Abbott Laboratories for the manufacture of bleomycin for use in the US in its MedPulsar system after regulatory approval had been granted for its use in the treatment of solid tumours. In a separate supply agreement, Faulding Inc. has agreed to manufacture bleomycin for Genetronic for use in Canada after regulatory approval had been granted. The MedPulsar Electroporation Therapy System with bleomycin is currently in phase III pivotal studies in the US as a treatment for recurrent and second primary squamous cell carcinomas of the head and neck. Genetronics received approval for the Electroporation Therapy system as a device in March 1999 when it achieved CE Mark certification. In February 2004, Genetronics announced that it had completed a Special Protocol Assessment review process with the US FDA for two new trials that will compare bleomycin electroporation therapy to surgery. The primary endpoint will be tissue and function preservation rather than survival. One proposal is for recurrent head and neck cancer, and the other is for disfiguring cutaneous cancer. Three Institutional Review Boards in the US have approved the two protocols and Genetronics has initiated enrollment. In June 2004, Genetronics was granted fast-track status for its MedPulsar Electroporation Therapy System clinical development programme for patients with head and neck cancer. Shifting from a primary endpoint of survival to a quality-of-life outcome will enable those clinical trials to be carried out faster with less cost and with a higher likelihood of success. As a result, Genetronic's phase III trials focussing on survival as a primary endpoint have been discontinued. This includes a phase III trial for late-stage, recurrent head and neck cancer in combination with the normal standard of treatment compared with normal standard of treatment alone. Interim results from this trial had suggested bleomycin electroporation therapy demonstrated local tumour control and preservation of organ function, as well as non-inferiority when compared with surgery. This trial was initiated in May 2002. In March 2004, Genetronics initiated a post-European regulatory approval clinical study in patients with primary or recurrent squamous cell carcinoma of the head and neck (SCCHN). This study aims to enroll approximately 100 patients at 12-15 hospitals located in the UK, Germany, Italy, France, Austria and other western European countries. The study is designed to support the commercialisation of the MedPulser Electroporation System in the EU. Prior clinical trials established the safety and performance of the MedPulser System for the treatment of SCCHN, leading to approval for sale in the EU based on achieving the CE Mark. This study will document the clinical and pharmacoeconomic benefit in support of reimbursement approval throughout Western Europe, establish centres of excellence to facilitate early sales, create a reference and customer base for a projected European commercial launch in 2005, and generate safety and efficacy data to support marketing applications in the US. The bleomycin delivery system has completed phase IIB trials in the US, Canada and Europe in patients with squamous cell carcinoma of the head and neck who have failed conventional therapies. Phase II data were submitted to the FDA in the first quarter of 2002 and a phase III trial was launched in May 2002. The therapy is also being used in France in patients with cancers of the head and neck, liver (metastatic) and melanoma. A review of the data from these phase II trials was completed in April 2001. In June 2004, Genetronics was granted two US patents. US patent 6,748,265 covers its trans-surface drug and gene delivery technology and provides additional proprietary rights for an apparatus and method to deliver genes, drugs and other molecules through tissue surfaces. The second US patent, 6,746,441, pertains to the field of ex vivo therapies and covers the introduction of molecules into cells by electroporation, either in a continuous-flow or batch mode, with a variable electric field orientation. In July 2004, Genetronics received a US patent (no. 6,763,264) covering methods for the in vivo delivery of a recombinant expression vector (DNA) or a pharmaceutical agent into tissue cells, and a method for the therapeutic application of electroporation to a patient to introduce macromolecules. Copyright 2004 Adis Data Information BV

Food grade microemulsion systems: Sunflower oil/castor oil derivative-ethanol/water. Rheological and physicochemical analysis.

PubMed

Mori Cortés, Noelia; Lorenzo, Gabriel; Califano, Alicia N

2018-05-01

Microemulsions are thermodynamically stable systems that have attracted considerable attention in the food industry as delivery systems for many hydrophobic nutrients. These spontaneous systems are highly dependent on ingredients and composition. In this work phase diagrams were constructed using two surfactants (Kolliphor RH40 and ELP), water, sunflower oil, and ethanol as cosurfactant, evaluating their physicochemical properties. Stability of the systems was studied at 25 and 60 °C, monitoring turbidity at 550 nm for over a month to identify the microemulsion region. Conductivity was measured to classify between water-in-oil and oil-in-water microemulsions. The phase diagram constructed with Kolliphor RH40 exhibited a larger microemulsion area than that formulated with Kolliphor ELP. All formulations showed a monomodal droplet size distribution with low polydispersity index (<0.30) and a mean droplet size below 20 nm. Systems with higher water content presented a Newtonian behavior; increasing the dispersed phase content produced a weak gel-like structure with pseudoplastic behavior under flow conditions that was satisfactorily modeled to obtain structural parameters. Copyright © 2018 Elsevier Ltd. All rights reserved.

Expanding Alternative Delivery Systems.

ERIC Educational Resources Information Center

Baltzer, Jan A.

Alternative educational delivery systems that might be useful to community colleges are considered. The following categories of delivery systems are covered: broadcast delivery systems; copy delivery systems, print delivery systems, computer delivery systems, telephone delivery systems, and satellites. Among the applications for broadcast…

PHASE-SHIFT, STIMULI-RESPONSIVE PERFLUOROCARBON NANODROPLETS FOR DRUG DELIVERY TO CANCER

PubMed Central

2012-01-01

This review focuses on phase-shift perfluorocarbon nanoemulsions whose action depends on an ultrasound-triggered phase shift from a liquid to gas state. For drug-loaded perfluorocarbon nanoemulsions, microbubbles are formed under the action of tumor-directed ultrasound and drug is released locally into tumor volume in this process. This review covers in detail mechanisms involved in the droplet-to-bubble transition as well as mechanisms of ultrasound-mediated drug delivery. PMID:22730185

Hierarchical drug release of pH-sensitive liposomes encapsulating aqueous two phase system.

PubMed

Zhang, Xunan; Zong, Wei; Bi, Hongmei; Zhao, Kunming; Fuhs, Thomas; Hu, Ying; Cheng, Wenlong; Han, Xiaojun

2018-06-01

As promising drug delivery vehicles, previous investigations of liposomes as carriers are primarily focused on insertion and modification of lipid membrane interfaces. The utility of the inner core seems to be overlooked. Herein, we developed pH-sensitive liposomes (PSLs) containing an aqueous two phase system (ATPS), and intriguingly discovered their hierarchical release under acidic stimuli. ATPS containing two polymers (poly(ethylene glycol) (PEG) and dextran) is homogeneous above phase transition temperature when producing ATPS-liposomes, and separated into PEG-rich phase and dextran-rich phase after cooling down to room temperature. The overall release time of ATPS-liposomes is divided into two stages and prolonged compared to simple aqueous liposomes. The unique release profile is due to the disproportional distribution of drugs in two phases. Doxorubicin (DOX) is loaded in the ATPS-liposomes, and their half maximum inhibition concentration on HeLa cells is 0.018 μmol L -1 , which means 27.5 fold increase in inhibition efficiency over free DOX. Copyright © 2018 Elsevier B.V. All rights reserved.

Induction of instability in water-in-oil-in-water double emulsions by freeze-thaw cycling.

PubMed

Rojas, Edith C; Papadopoulos, Kyriakos D

2007-06-19

Individual water-in-oil-in-water (W1/O/W2) double-emulsion globules loaded with fluorescently labeled bovine serum albumin (FITC-BSA) were optically monitored within cylindrical capillaries during freeze-thaw cycling. Coalescence of internal aqueous droplets (W1) and external aqueous phase (W2), termed external coalescence, was not observed before or during freezing of the oil phase (O). On the other hand, this instability mechanism was readily promoted during thawing. This realization confirms the previously suggested potential of W1/O/W2 double emulsions to trigger release upon oil thawing and demonstrates that it is a direct result of globule breakage through external coalescence. The presented results also identified a threshold in the relative W1 droplet size above which instability occurred, while smaller droplets remained unperturbed and therefore indicate that optimization of the delivery can be achieved by tuning the size of W1 droplets. In addition, we propose a possible explanation for the occurrence of instability during oil thawing and its dependence on the size of W1 droplets. Because this alternative globule-breakage mechanism simply uses temperature increase (solid-to-liquid-phase transition) as external stimulus, W1/O/W2 double-emulsion delivery systems can be easily tailored by choosing an oil phase with the appropriate phase-transition temperature.

Antibacterial chitosan coating on nano-hydroxyapatite/polyamide66 porous bone scaffold for drug delivery.

PubMed

Huang, Di; Zuo, Yi; Zou, Qin; Zhang, Li; Li, Jidong; Cheng, Lin; Shen, Juan; Li, Yubao

2011-01-01

This study describes a new drug-loaded coating scaffold applied in infection therapy during bone regeneration. Chitosan (CS) containing antibacterial berberine was coated on a nano-hydroxyapatite/polyamide66 (n-HA/PA66) scaffold to realize bone regeneration together with antimicrobial properties. The porous scaffold was fabricated using the phase-inversion method with a porosity of about 84% and macropore size of 400-600 μm. The morphology, mechanical properties and drug-release behavior were investigated at different ratios of chitosan to berberine. The results show that the elastic modulus and compressive strength of the coated scaffolds were improved to 35.4 MPa and 1.7 MPa, respectively, about 7 times and 3 times higher than the uncoated scaffolds. After a burst release of berberine within the first 3 h in PBS solution, a continuous berberine release can last 150 h, which is highly dependent on the coating concentration and suitable for antibacterial requirement of orthopaedic surgery. The bactericidal test confirms a strong antibiotic effect of the delivery system and the minimum inhibitory concentration of the drug is 0.02 mg/ml. Moreover, in vitro biological evaluation demonstrates that the coating scaffolds act as a good matrix for MG63 adhesion, crawl, growth and proliferation, suggesting that the antibacterial delivery system has no cytotoxicity. We expect the drug-delivery system to have a potential application in bone regeneration or defect repair.

Managing ulcerative colitis in remission phase: usefulness of Casperome®, an innovative lecithin-based delivery system of Boswellia serrata extract.

PubMed

Pellegrini, L; Milano, E; Franceschi, F; Belcaro, G; Gizzi, G; Feragalli, B; Dugall, M; Luzzi, R; Togni, S; Eggenhoffner, R; Giacomelli, L

2016-06-01

Boswellia serrata extracts (BSE) have been traditionally used for the treatment of several inflammatory diseases. The aim of this study was to evaluate the efficacy of a novel delivery form of BSE (Casperome®) in Ulcerative Colitis (UC) during minimally symptomatic remission phase. In this open-label, observational, registry study, informed participants with UC in remission phase (n = 43) freely decided to receive the oral daily Casperome® supplementation (n = 22) or no supplementation (n = 21) for 4 weeks. Several parameters associated with minimally symptomatic UC in remission were evaluated at the inclusion and the end of the study. A significant beneficial effect of Casperome® was observed for all the parameters evaluated, namely: diffuse intestinal pain, evident and occult blood in stools, bowel movements and cramps, watery stools, malaise, anemia, rectal involvement, number of white blood cells as well as need for concomitant drugs and medical attention. Faecal concentration of calprotectin, a marker of bowel inflammation, resulted ameliorated in Casperome® supplemented patients. Our study showed that Casperome® supplementation attenuates symptoms associated with mild UC in remission, reducing the use of drugs and medical consultations. Therefore, our study suggests that Casperome® supplementation could represent a promising alternative approach to manage minimally symptomatic UC and maintain the remission phase.

Reinforcing the inner phase of the filled hydrogels with CNTs alters drug release properties and human keratinocyte morphology: A study on the gelatin- tamarind gum filled hydrogels.

PubMed

Maharana, Vivek; Gaur, Deepanjali; Nayak, Suraj K; Singh, Vinay K; Chakraborty, Subhabrata; Banerjee, Indranil; Ray, Sirsendu S; Anis, Arfat; Pal, Kunal

2017-11-01

The study reports the synthesis and characterization of gelatin-tamarind gum (TG) based filled hydrogels for drug delivery applications. In this study, three different types of carbon nanotubes (CNTs) were incorporated within the dispersed TG phase of the filled hydrogels. The prepared hydrogels were thoroughly characterised using bright field microscope, FESEM, FTIR spectroscopy, differential scanning calorimeter, and mechanical tester. The swelling and the drug (salicylic acid) release properties of the filled hydrogels were also evaluated. The micrographs revealed the formation of biphasic systems. The internal phase appeared as agglomerates, and the CNTs were confined within the dispersed TG phase. FTIR and XRD studies revealed that CNTs promoted associative interactions among the components of the hydrogel, which promoted the formation of large crystallite size. The mechanical study indicated better resistance to the breakdown of the architecture of the CNT-containing filled hydrogels. Drug release studies, both passive and iontophoretic, suggested that the non-Fickian diffusion of the drug was prevalent during its release from hydrogel matrices. The prepared hydrogels were cytocompatible with human keratinocytes. The results suggested the probable use of such hydrogels in wound healing, tissue engineering and drug delivery applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Webcam Delivery of the Camperdown Program for Adolescents Who Stutter: A Phase I Trial

ERIC Educational Resources Information Center

Carey, Brenda; O'Brian, Sue; Onslow, Mark; Packman, Ann; Menzies, Ross

2012-01-01

Purpose: This Phase I clinical trial explored the viability of webcam Internet delivery of the Camperdown Program for adolescents who stutter. Method and Procedure: Participants were 3 adolescents ages 13, 15, and 16 years, with moderate-severe stuttering. Each was treated with the Camperdown Program delivered by webcam with no clinic attendance.…

Development of an injectable PHBV microparticles-GG hydrogel hybrid system for regenerative medicine.

PubMed

Pacheco, Daniela P; Amaral, Maria H; Reis, Rui L; Marques, Alexandra P; Correlo, Vítor M

2015-01-15

Uncontrollable displacements that greatly affect the concentration of active agents at the target tissues are among a major limitation of the use of microparticulate drug delivery systems (DDS). Under this context a biphasic injectable DDS combining poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles (MPs) and a gellan gum (GG) injectable hydrogel is herein proposed for the localized delivery and long-term retention of MPs carrying hydrophilic and hydrophobic model active agents. A double emulsion-solvent evaporation method was adopted to develop the PHBV MPs, carrying bovine serum albumin (BSA) or dexamethasone (Dex) as hydrophilic and hydrophobic active agents' models, respectively. Moreover, this method was modified, together with the properties of the hydrogel to tailor the delivery profile of the active agents. Variations of the composition of the organic phase during the process allowed tuning surface topography, particle size distribution and core porosity of the PHBV MPs and, thus, the in vitro release profile of Dex but not of BSA. Besides, after embedding hydrogels of higher GG concentration led to a slower and more sustained release of both active agents, independently of the processing conditions of the microparticulate system. Copyright © 2014 Elsevier B.V. All rights reserved.

Golden beam data for proton pencil-beam scanning.

PubMed

Clasie, Benjamin; Depauw, Nicolas; Fransen, Maurice; Gomà, Carles; Panahandeh, Hamid Reza; Seco, Joao; Flanz, Jacob B; Kooy, Hanne M

2012-03-07

Proton, as well as other ion, beams applied by electro-magnetic deflection in pencil-beam scanning (PBS) are minimally perturbed and thus can be quantified a priori by their fundamental interactions in a medium. This a priori quantification permits an optimal reduction of characterizing measurements on a particular PBS delivery system. The combination of a priori quantification and measurements will then suffice to fully describe the physical interactions necessary for treatment planning purposes. We consider, for proton beams, these interactions and derive a 'Golden' beam data set. The Golden beam data set quantifies the pristine Bragg peak depth-dose distribution in terms of primary, multiple Coulomb scatter, and secondary, nuclear scatter, components. The set reduces the required measurements on a PBS delivery system to the measurement of energy spread and initial phase space as a function of energy. The depth doses are described in absolute units of Gy(RBE) mm² Gp⁻¹, where Gp equals 10⁹ (giga) protons, thus providing a direct mapping from treatment planning parameters to integrated beam current. We used these Golden beam data on our PBS delivery systems and demonstrated that they yield absolute dosimetry well within clinical tolerance.

Controlled, sustained release of proteins via an injectable, mineral-coated microsphere delivery vehicle

NASA Astrophysics Data System (ADS)

Franklin-Ford, Travelle

Hydroxyapatite interfaces have demonstrated strong protein binding and protein selection from a passing solution and can serve as a biocompatible carrier for controlled protein delivery. Hydroxyapatite is a major component of long bones and tooth enamel and is the most stable of all calcium phosphate isoforms in aqueous solutions at physiologic pH, providing a sensitive chromatographic mechanism for separating proteins. Here we describe an approach to create a synthetic hydroxyapatite coating through a biomimetic, heterogeneous nucleation from a modified simulated body fluid--supersaturated with calcium and phosphate ions on the surface of injectable polymer microspheres. We are able to bind and release bioactive growth factors into a variety of in vitro and in vivo conditions, demonstrating the functionality and advantage of the biomaterial. Creating a hydroxyapatite layer on the Poly(D,L-lactide-co-glycolide) (PLG) microsphere surface, avails the microsphere interior for another application that will not compete with protein binding and release. Encapsulating an imaging agent within the aqueous phase of the emulsion provides a visual reference for the injectable therapy upon microsphere fabrication. Another advantage of this system is that the mineral coating and subsequent protein binding is not compromised by the encapsulated imaging agent. This dual function delivery vehicle is not only advantageous for spatial tracking therapeutic applications, but also determining the longevity of the delivery vehicle once injected. In the broader sense, providing a mechanism to image and track our temporally controlled, sustained delivery system gives more evidence to support the effects of released protein on in vivo responses (bioactivity) and locate microspheres within different biological systems.

Upper Atmosphere Research Satellite (UARS) science data processing center implementation history

NASA Technical Reports Server (NTRS)

Herring, Ellen L.; Taylor, K. David

1990-01-01

NASA-Goddard is responsible for the development of a ground system for the Upper Atmosphere Research Satellite (UARS) observatory, whose launch is scheduled for 1991. This ground system encompasses a dedicated Central Data Handling Facility (CDHF); attention is presently given to the management of software systems design and implementation phases for CDHF by the UARS organization. Also noted are integration and testing activities performed following software deliveries to the CDHF. The UARS project has an obvious requirement for a powerful and flexible data base management system; an off-the-shelf commercial system has been incorporated.

TU-E-BRB-08: Dual Gated Volumetric Modulated Arc Therapy.

PubMed

Wu, J; Fahimian, B; Wu, H; Xing, L

2012-06-01

Gated Volumetric Modulated Arc Therapy (VMAT) is an emerging treatment modality for Stereotactic Body Radiotherapy (SBRT). However, gating significantly prolongs treatment time. In order to enhance treatment efficiency, a novel dual gated VMAT, in which dynamic arc deliveries are executed sequentially in alternating exhale and inhale phases, is proposed and evaluated experimentally. The essence of dual gated VMAT is to take advantage of the natural pauses that occur at inspiration and exhalation by alternatively delivering the dose at the two phases, instead of the exhale window only. The arc deliveries at the two phases are realized by rotating gantry forward at the exhale window and backward at the inhale in an alternative fashion. Custom XML scripts were developed in Varian's TrueBeam STx Developer Mode to enable dual gated VMAT delivery. RapidArc plans for a lung case were generated for both inhale and exhale phases. The two plans were then combined into a dual gated arc by interleaving the arc treatment nodes of the two RapidArc plans. The dual gated plan was delivered in the development mode of TrueBeam LINAC onto a motion phantom and the delivery was measured by using pinpoint chamber/film/diode array (delta 4). The measured dose distribution was compared with that computed using Eclipse AAA algorithm. The treatment delivery time was recorded and compared with the corresponding single gated plans. Relative to the corresponding single gated delivery, it was found that treatment time efficiency was improved by 95.5% for the case studied here. Pinpoint chamber absolute dose measurement agreed the calculation to within 0.7%. Diode chamber array measurements revealed that 97.5% of measurement points of dual gated RapidArc delivery passed the 3% and 3mm gamma-test criterion. A dual gated VMAT treatment has been developed and implemented successfully with nearly doubled treatment delivery efficiency. © 2012 American Association of Physicists in Medicine.

Enhanced Remedial Amendment Delivery through Fluid Viscosity Modifications: Experiments and numerical simulations

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

Zhong, Lirong; Oostrom, Martinus; Wietsma, Thomas W.

2008-07-29

Abstract Heterogeneity is often encountered in subsurface contamination characterization and remediation. Low-permeability zones are typically bypassed when remedial fluids are injected into subsurface heterogeneous aquifer systems. Therefore, contaminants in the bypassed areas may not be contacted by the amendments in the remedial fluid, which may significantly prolong the remediation operations. Laboratory experiments and numerical studies have been conducted to develop the Mobility-Controlled Flood (MCF) technology for subsurface remediation and to demonstrate the capability of this technology in enhancing the remedial amendments delivery to the lower permeability zones in heterogeneous systems. Xanthan gum, a bio-polymer, was used to modify the viscositymore » of the amendment-containing remedial solutions. Sodium mono-phosphate and surfactant were the remedial amendment used in this work. The enhanced delivery of the amendments was demonstrated in two-dimensional (2-D) flow cell experiments, packed with heterogeneous systems. The impact of polymer concentration, fluid injection rate, and permeability contract in the heterogeneous systems has been studied. The Subsurface Transport over Multiple Phases (STOMP) simulator was modified to include polymer-induced shear thinning effects. Shear rates of polymer solutions were computed from pore-water velocities using a relationship proposed in the literature. Viscosity data were subsequently obtained from empirical viscosity-shear rate relationships derived from laboratory data. The experimental and simulation results clearly show that the MCF technology is capable of enhancing the delivery of remedial amendments to subsurface lower permeability zones. The enhanced delivery significantly improved the NAPL removal from these zones and the sweeping efficiency on a heterogeneous system was remarkably increased when a polymer fluid was applied. MCF technology is also able to stabilize the fluid displacing front when there is a density difference between the fluids. The modified STOMP simulator was able to predict the experimental observed fluid displacing behavior. The simulator may be used to predict the subsurface remediation performance when a shear thinning fluid is used to remediate a heterogeneous system.« less

Time delay compensation for closed-loop insulin delivery systems: a simulation study.

PubMed

Reboldi, G P; Home, P D; Calabrese, G; Fabietti, P G; Brunetti, P; Massi Benedetti, M

1991-06-01

Closed loop insulin therapy certainly represents the best possible approach to insulin replacement. However, present limitations preclude wider application of the so-called artificial pancreas. Therefore, a thorough understanding of these limitations is needed to design better systems for future long-term use. The present simulation study was design: to obtain better information on the impact of the measurement delay of currently available closed-loop devices both during closed-loop insulin delivery and blood glucose clamp studies, and to design and test a time delay compensator based on the method originally described by O.J. Smith. Simulations were performed on a Compaq Deskpro 486/25 personal computer under MS-DOS operating system using Simnon rel. 3.00 software. There was a direct relationship between measurement delay and amount of insulin delivered, i.e., the longer the delay the higher the insulin dose needed to control a rise in blood glucose; the closed-loop response in presence of a time delay was qualitatively impaired both during insulin delivery and blood glucose clamp studies; time delay compensation was effective in reducing the insulin dose and improving controller stability during the early phase of clamp studies. However, the robustness of a Smith's predictor-based controller should be carefully evaluated before implementation in closed-loop systems can be considered.

A Review of Injectable Polymeric Hydrogel Systems for Application in Bone Tissue Engineering.

PubMed

Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Marimuthu, Thashree; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

2016-11-21

Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive manner. The success of bioengineered injectable tissue modified delivery systems depends significantly on their chemical, physical and biological properties. Irrespective of shape and defect geometry, injectable therapy has an unparalleled advantage in which intricate therapy sites can be effortlessly targeted with minimally invasive procedures. Using material testing, it was found that properties of stimuli-responsive hydrogel systems enhance cellular responses and cell distribution at any site prior to the transitional phase leading to gelation. The substantially hydrated nature allows significant simulation of the extracellular matrix (ECM), due to its similar structural properties. Significant current research strategies have been identified and reported to date by various institutions, with particular attention to thermo-responsive hydrogel delivery systems, and their pertinent focus for bone tissue engineering. Research on future perspective studies which have been proposed for evaluation, have also been reported in this review, directing considerable attention to the modification of delivering natural and synthetic polymers, to improve their biocompatibility and mechanical properties.

Development and in vivo evaluation of self-microemulsion as delivery system for α-mangostin.

PubMed

Xu, Wen-Ke; Jiang, Hui; Yang, Kui; Wang, Ya-Qin; Zhang, Qian; Zuo, Jian

2017-03-01

α-Mangostin (MG) is a versatile bioactive compound isolated from mangosteen and possesses significant pharmacokinetic shortages. To augment the potential clinical efficacy, MG-loaded self-microemulsion (MG-SME) was designed and prepared in this study, and its potential as a drug loading system was evaluated based on the pharmacokinetic performance and tissue distribution feature. The formula of MG-SME was optimized by an orthogonal test under the guidance of ternary phase diagram, and the prepared MG-SME was characterized by encapsulation efficiency, size distribution, and morphology. Optimized high performance liquid chromatography method was employed to determine concentrations of MG and characterize the pharmacokinetic and tissue distribution features of MG in rodents. It was found that diluted MG-SME was characterized as spherical particles with a mean diameter of 24.6 nm and an encapsulation efficiency of 87.26%. The delivery system enhanced the area under the curve of MG by 4.75 times and increased the distribution in lymphatic organs. These findings suggested that SME as a nano-sized delivery system efficiently promoted the digestive tract absorption of MG and modified its distribution in tissues. The targeting feature and high oral bioavailability of MG-SME promised a good clinical efficacy, especially for immune diseases. Copyright © 2017. Published by Elsevier Taiwan.

Ethinyl estradiol and levonorgestrel in a transdermal contraceptive delivery system.

PubMed

Sriprasert, Intira; Stanczyk, Frank Z; Archer, David F

2015-01-01

The new transdermal contraceptive delivery system (TCDS) developed by Agile Therapeutics containing ethinyl estradiol and levonorgestrel (EE/LNG) is a reversible contraceptive method that maintains stable serum levels of both estrogen and progestin, and has efficacy similar to that of combination oral contraceptives (COC). We provided information of this new TCDS compared with the only TCDS available on the market that contains EE and norelgestromin, and has a higher EE exposure than a COC with 35 µg of EE potentially increasing the risk of venous thromboembolism. The article will summarize finding from clinical studies Phase I, II and III of EE/LNG TCDS. The development of the lower dose EE/LNG TCDS has demonstrated less EE exposure. The serum levels of EE and LNG were stable and comparable between various application sites and daily life conditions. Moreover, the EE/LNG TCDS showed comparable efficacy among obese and non-obese users. However, the Pearl index of this EE/LNG TCDS is questionable and the problem of compliance is a potential confounder of the results. The current Phase III efficacy study will contribute to a further evaluation of compliance and efficacy and will be completed in 2016.

Solubility of ocular therapeutic agents in self-emulsifying oils. I. Self-emulsifying oils for ocular drug delivery: solubility of indomethacin, aciclovir and hydrocortisone.

PubMed

Czajkowska-Kośnik, Anna; Sznitowska, Małgorzata

2009-01-01

Self-emulsifying drug delivery systems (SEDDS) were prepared by dissolving Cremophor EL, Tween 20, Tween 80 and Span 80 (1% or 5%) in oils (Miglyol 812 or castor oil). Solubilities of three ophthalmic drugs, namely aciclovir, hydrocortisone and indomethacin were determined in these systems. In addition, the effect of a small amount of water (0.5% and 2%) on solubilization properties of the systems was estimated. Of the three substances, indomethacin showed the best solubility in Miglyol while aciclovir was practically insoluble in this oil. The surfactants usually increased drug solubility in the oily phase. Only Tween 20 was found to decrease the solubility of aciclovir and hydrocortisone in Miglyol. Addition of a small amount of water to the oil/surfactant system increased solubility of hydrocortisone, but not of indomethacin. The results of the current study may be utilized to design a suitable composition of SEDDS and allow continuation of research on this type of drug carriers.

High-precision piezo-ejection ocular microdosing: Phase II study on local and systemic effects of topical phenylephrine.

PubMed

Ianchulev, Tsontcho; Weinreb, Robert; Tsai, James C; Lin, Shan; Pasquale, Louis R

2018-01-01

Conventional eyedropper-delivered volumes (25-50 µl) exceed the eye's usual tear-film volume (7 µl) and precorneal reservoir capacity, risking overflow and ocular/systemic complications. Piezoelectric high-precision microdosing may circumvent these limitations. Results & methodology: In this masked, nonrandomized, cross-over study, subjects (n = 12) underwent pupil dilation with topical phenylephrine (PE) administered by 32-µl eyedropper (2.5% or 10% formulation) and 8-µl electronic microdosing (10% formulation). Microdosing with PE-10% achieved comparable peak dilation as 10% eyedropper-delivery and superior dilation to 2.5% eyedropper-delivery (p = 0.009) at 75 min. Microdosing significantly reduced 20-min plasma PE levels versus PE10% eyedropper; neither treatment altered heart rate/blood pressure. Eye irritation occurred significantly less frequently with microdosing than PE10% eyedrops. Piezo-ejection PE microdosing achieves comparable biological effect as eyedropper dosing; reduced systemic absorption may decrease risk of systemic side effects.

Discontinuing Oxytocin Infusion in the Active Phase of Labor: A Systematic Review and Meta-analysis.

PubMed

Saccone, Gabriele; Ciardulli, Andrea; Baxter, Jason K; Quiñones, Joanne N; Diven, Liany C; Pinar, Bor; Maruotti, Giuseppe Maria; Martinelli, Pasquale; Berghella, Vincenzo

2017-11-01

To evaluate the benefits and harms of discontinuation of oxytocin after the active phase of labor is reached. Electronic databases (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from their inception until April 2017. We included all randomized controlled trials comparing discontinuation (ie, intervention group) and continuation (ie, control group) of oxytocin infusion after the active phase of labor is reached, either after induction or augmentation of labor. Discontinuation of oxytocin infusion was defined as discontinuing oxytocin infusion when the active phase of labor was achieved. Continuation of oxytocin infusion was defined as continuing oxytocin infusion until delivery. Only trials in singleton gestations with vertex presentation at term were included. The primary outcome was the incidence of cesarean delivery. Nine randomized controlled trials, including 1,538 singleton gestations, were identified as relevant and included in the meta-analysis. All nine trials included only women undergoing induction of labor. In the discontinuation group, if arrest of labor occurred, usually defined as no cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or more, oxytocin infusion was restarted. Women in the control group had oxytocin continued until delivery usually at the same dose used at the time the active phase was reached. Women who were randomized to have discontinuation of oxytocin infusion after the active phase of labor was reached had a significantly lower risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI 0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk 0.53, 95% CI 0.33-0.84) compared with those who were randomized to have continuation of oxytocin infusion until delivery. Discontinuation of oxytocin infusion was associated with an increase in the duration of the active phase of labor (mean difference 27.65 minutes, 95% CI 3.94-51.36). In singleton gestations with cephalic presentation at term undergoing induction, discontinuation of oxytocin infusion after the active phase of labor at approximately 5 cm is reached reduces the risk of cesarean delivery and of uterine tachysystole compared with continuous oxytocin infusion. Given this evidence, discontinuation of oxytocin infusion once the active stage of labor is established in women being induced should be considered as an alternative management plan.

Women's acute anxiety variations before and after epidural anesthesia for childbirth.

PubMed

Fernández-Campos, Francisco J; Escrivá, Dolores; Palanca, José M; Ridocci, Francisca; Barrios, Carlos; Gallego, Juan

2017-06-01

This study assessed changes in anxiety during different phases of childbirth in a sample of women demanding epidural anesthesia. Prospective, longitudinal case series. A total of 133 women who demanded epidural anesthesia for childbirth answered the questionnaires. Anxiety state was measured using the State Trait Anxiety Inventory (STAI) questionnaire. The STAI-S (anxiety state) was administered in three phases during childbirth: Phase 1 was before applying epidural anesthesia, Phase 2 was 45 min after the application of epidural anesthesia and Phase 3 was at less than 24 h after delivery. Data were collected in two general hospitals: a third-level public hospital and a well-recognized private hospital. STAI scores. Anxiety state decreases significantly after applying the epidural anesthesia (Phase 2) compared to before anesthesia (Phase 1), and it remains low levels 24 h after childbirth (Phase 3). There were statistically significant differences in STAI scores between the different phases administrated (Phases 1 and 2: p < 0.001; effect size, d = 1.40; Phases 1 and 3: p < 0.001; effect size, d = 1.39). In Phase 3, women with cesarean section birth had significant differences in STAI scores relative to those with spontaneous birth (p = 0.037; d = 0.44). The type of health-care setting (public or private), the educational level and the numbers of previous births does not affect the level of anxiety state in women in any of the three phases. Women's anxiety decreases significantly after applying epidural anesthesia, and it remains low 24 h after delivery. Anxiety against childbirth was not influenced by the health system used by women, by the condition of primiparous or multiparous, or by the educational level. Women who received an epidural anesthesia with a cesarean section reported higher rates of anxiety state after birth.

Radio-over-optical waveguide system-on-wafer for massive delivery capacity 5G MIMO access networks

NASA Astrophysics Data System (ADS)

Binh, Le N.

2017-01-01

Delivering maximum information capacity over MIMO antennae systems beam steering is critical so as to achieve the flexibility via beam steering, maximizing the number of users or community of users in Gb/s rate per user over distributed cloud-based optical-wireless access networks. This paper gives an overview of (i) demands of optical - wireless delivery with high flexibility, especially the beam steering of multi-Tbps information channels to information hungry community of users via virtualized beam steering MIMO antenna systems at the free-license mmW region; (ii) Proposing a novel photonic planar integrated waveguide systems composing several passive and active, passive and amplification photonic devices so as to generate mmW carrier and embedded baseband information channels to feed to antenna elements; (iii) Integration techniques to generate a radio over optical waveguide (RoOW) system-on-wafer (SoW) comprising MIMO planar antenna elements and associate photonic integrated circuits for both up- and down- links; (iv) Challenges encountered in the implementation of the SoW in both wireless and photonic domains; (v) Photonic modulation techniques to achieve maximum transmission capacity per wavelength per MIMO antenna system. (vi) A view on control-feedback systems for fast and accurate generation of phase pattern for MIMO beam steering via a bank of optical phase modulators to mmW carrier phases and their preservation in the converted mmW domain . (vi) The overall operational principles of the novel techniques and technologies based on the coherent mixing of two lightwave channels The entire SoW can be implemented on SOI Si-photonic technology or via hybrid integration. These technological developments and their pros- and cons- will be discussed to achieve 50Tera-bps over the extended 110 channel Cband single mode fiber with mmW centered at 58.6GHz and 7GHz free-license band.

Nanomedicine for therapeutic drug therapy: Approaches to increase the efficacy of drug therapy with nanoemulsion delivery and reduce the toxicity of quantum dots

NASA Astrophysics Data System (ADS)

Kambalapally, Swetha Reddy

The advancement of nanotechnology has paved the way for novel nanoscale materials for use in a wide range of applications. The use of these nanomaterials in biomedicine facilitates the improvement of existing technologies for disease prevention and treatment through diagnostics, tumor detection, drug delivery, medical imaging and vaccine development. Nanotechnology delivery systems for therapeutic uses includes the formulation of nanoparticles in emulsions. These novel delivery systems can improve drug efficacy by their ability to enhance bioavailability, minimize drug side effects, decrease drug toxicity, provide targeted site delivery and increase circulation of the drug in the blood. Additionally, these delivery systems also improve the drug stability and encapsulation efficiency. In the Introduction, this thesis will describe a novel technique for the preparation of nanoemulsions which was utilized in drug delivery and diagnostic applications. This novel Phase Inversion Temperature (PIT) method is a solvent and polymer-free and low energy requiring emulsification method, typically utilizing oils stabilized by nonionic surfactants to prepare water in oil (W/O) emulsions. The correlation between the particle size, zeta potential and the emulsion stability is described. The use of this nanoemulsion delivery system for pharmaceuticals and nutraceuticals by utilizing in vitro systems was investigated. Using the PIT method, a self assembling nanoemulsion (SANE) of gamma Tocotrienols (gammaT3), a component of Vitamin E family has been demonstrated to reduce cholesterol accumulation in HepG-2 cells. The nanoemulsion is stable and the particle size is around 20 nm with a polydispersity index (PDI) of 0.065. The effect of the nano gammaT3 on the metabolism of cholesterol, HMG-CoA activity and Apo-B levels were evaluated in an in vitro system utilizing HepG2 cells. A new class of nanoparticles, Quantum dots (QDs) has shown immense potential as novel nanomaterials used as fluorescent labels. They have been studied extensively due to their interesting optical and electrical properties. The study of their applications has led to their use as novel platforms for delivery into living systems for use in medical imaging. The second part of this thesis discusses the toxicity of the various semiconductor nanocrystals, CdSe and InP. The results show the toxicity of CdSe and InP QDs in in vitro cultures of whole skin biopsies exposed to similar concentrations. This forms the basis for further studies involving QDs and approaches to reduce the toxicity of these nanoparticles. Finally, ligand exchange mediated Solutol HS-15 modified CdSe QDs were prepared for the first time. The modified CdSe QDs demonstrated long term stability and reduced cytotoxicity. Such behavior is interpreted as arising from decreased aggregation of the QDs due to the incorporation of the surfactant.

Comparative permeability studies with radioactive and nonradioactive risedronate sodium from self-microemulsifying drug delivery system and solution.

PubMed

Ilem-Ozdemir, Derya; Gundogdu, Evren; Ekinci, Meliha; Ozgenc, Emre; Asikoglu, Makbule

2015-01-01

The purpose of this work is to prepare a self-microemulsifying drug delivery system (SMEDDS) for risedronate sodium (RSD) and to compare the permeability with RSD solution. The solubility of RSD was determined in different vehicles. Phase diagrams were constructed to determine the optimum concentration of oil, surfactant, and cosurfactant. RSD SMEDDS was prepared by using a mixture of soybean oil, cremophor EL, span 80, and transcutol (2.02:7.72:23.27:61.74, w/w, respectively). The prepared RSD SMEDDS was characterized by droplet size value. In vitro Caco-2 cell permeability studies were performed for SMEDDS and solution of radioactive ((99 m)Tc-labeled RSD) and nonradioactive RSD. The experimental results indicated that RSD SMEDDS has good stability and its droplet size is between 216.68 ± 3.79 and 225.26 ± 7.65 during stability time. In addition, RSD SMEDDS has higher permeability value than the RSD solution for both radioactive and nonradioactive experiments. The results illustrated the potential use of SMEDDS for delivery of poorly absorbed RSD.

The significance of transferrin receptors in oncology: the development of functional nano-based drug delivery systems.

PubMed

Tortorella, Stephanie; Karagiannis, Tom C

2014-01-01

Anticancer therapeutic research aims to improve clinical management of the disease through the development of strategies that involve currently-relevant treatment options and targeted delivery. Tumour-specific and -targeted delivery of compounds to the site of malignancy allows for enhanced cellular uptake, increased therapeutic benefit with high intratumoural drug concentrations, and decreased systemic exposure. Due to the upregulation of transferrin receptor expression in a wide variety of cancers, its function and its highly efficient recycling pathway, strategies involving the selective targeting of the receptor are well documented. Direct conjugation and immunotoxin studies using the transferrin peptide or anti-transferrin receptor antibodies as the targeting moiety have established the capacity to enhance cellular uptake, cross the blood brain barrier, limit systemic toxicity and reverse multi-drug resistance. Limitations in direct conjugation, including the difficulty in linking an adequate amount of therapeutic compound to the ligand or antibody have identified the requirement to develop novel delivery methods. The application of nanoparticulate theory in the development of functional drug delivery systems has proven to be most promising, with the ability to selectively modify size-dependent properties and surface chemistry. The transferrin modification on a range of nanoparticle formulations enhances selective cellular uptake through transferrin-mediated processes, and increases therapeutic benefit through the ability to encapsulate high concentrations of relevant drug to the tumour site. Although ineffective in crossing the blood brain barrier in its free form, chemotherapeutic compounds including doxorubicin, may be loaded into transferrin-conjugated nanocarriers and impart cytotoxic effects in glioma cells in vitro and in vivo. Additionally, transferrin-targeted nanoparticles may be used in selective diagnostic applications with enhanced selectivity and sensitivity. Four transferrin-modified nano-based drug delivery systems are currently in early phases of human clinical trials. Despite the collective promise, inconsistencies in some studies have exposed some limitations in current formulations and the difficulty in translating preliminary studies into clinically-relevant therapeutic options. The main objective of this review is to investigate the development of transferrin targeted nano-based drug delivery systems in order to establish the use of transferrin as a cancer-targeted moiety, and to ultimately evaluate the progression of cancer therapeutic strategies for future research.

Follicular delivery of spironolactone via nanostructured lipid carriers for management of alopecia.

PubMed

Shamma, Rehab Nabil; Aburahma, Mona Hassan

2014-01-01

Spironolactone (SL) is a US Food and Drug Administration-approved drug for the treatment of hypertension and various edematous conditions. SL has gained a lot of attention for treating androgenic alopecia due to its potent antiandrogenic properties. Recently, there has been growing interest for follicular targeting of drug molecules for treatment of hair and scalp disorders using nanocolloidal lipid-based delivery systems to minimize unnecessary systemic side effects associated with oral drug administration. Accordingly, the objective of this study is to improve SL efficiency and safety in treating alopecia through the preparation of colloidal nanostructured lipid carriers (NLCs) for follicular drug delivery. SL-loaded NLCs were prepared by an emulsion solvent diffusion and evaporation method using 23 full factorial design. All of the prepared formulations were spherical in shape with nanometric size range (215.6-834.3 nm) and entrapment efficiency >74%. Differential scanning calorimetry thermograms and X-ray diffractograms revealed that SL exists in amorphous form within the NLC matrices. The drug release behavior from the NLCs displayed an initial burst release phase followed by sustained release of SL. Confocal laser scanning microscopy confirmed the potential of delivering the fluorolabeled NLCs within the follicles, suggesting the possibility of using SL-loaded NLCs for localized delivery of SL into the scalp hair follicles.

Follicular delivery of spironolactone via nanostructured lipid carriers for management of alopecia

PubMed Central

Shamma, Rehab Nabil; Aburahma, Mona Hassan

2014-01-01

Spironolactone (SL) is a US Food and Drug Administration-approved drug for the treatment of hypertension and various edematous conditions. SL has gained a lot of attention for treating androgenic alopecia due to its potent antiandrogenic properties. Recently, there has been growing interest for follicular targeting of drug molecules for treatment of hair and scalp disorders using nanocolloidal lipid-based delivery systems to minimize unnecessary systemic side effects associated with oral drug administration. Accordingly, the objective of this study is to improve SL efficiency and safety in treating alopecia through the preparation of colloidal nanostructured lipid carriers (NLCs) for follicular drug delivery. SL-loaded NLCs were prepared by an emulsion solvent diffusion and evaporation method using 23 full factorial design. All of the prepared formulations were spherical in shape with nanometric size range (215.6–834.3 nm) and entrapment efficiency >74%. Differential scanning calorimetry thermograms and X-ray diffractograms revealed that SL exists in amorphous form within the NLC matrices. The drug release behavior from the NLCs displayed an initial burst release phase followed by sustained release of SL. Confocal laser scanning microscopy confirmed the potential of delivering the fluorolabeled NLCs within the follicles, suggesting the possibility of using SL-loaded NLCs for localized delivery of SL into the scalp hair follicles. PMID:25473283

Self-double-emulsifying drug delivery system (SDEDDS): a new way for oral delivery of drugs with high solubility and low permeability.

PubMed

Qi, Xiaole; Wang, Lishuang; Zhu, Jiabi; Hu, Zhenyi; Zhang, Jie

2011-05-16

Water-in-oil-in-water (w/o/w) double emulsions are potential for enhancing oral bioavailability of drugs with high solubility and low permeability, but their industrial application is limited due to the instability. Herein, we developed a novel formulation, self-double-emulsifying drug delivery systems (SDEDDS) by formulating mixtures of hydrophilic surfactants and water-in-oil (w/o) emulsions, which were easier to be stable through formulations optimization. SDEDDS can spontaneously emulsify to water-in-oil-in-water (w/o/w) double emulsions in the mixed aqueous gastrointestinal environment, with drugs encapsulated in the internal water phase of the double emulsions. We employed SDEDDS to improve the oral absorption of pidotimod, a peptide-like drug with high solubility and low permeability. The optimized pidotimod-SDEDDS were found to be stable up to 6 months under 25°C. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with SDEDDS showed 2.56-fold (p<0.05) increased absorption of pidotimod, compared to the pidotimod solution. Histopathologic studies confirmed that SDEDDS exerted absorption promoting effect without serious local damages. These studies demonstrate that SDEDDS may be a promising strategy for peroral delivery of peptide and peptidomimetic drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Role of self-emulsifying drug delivery systems in optimizing the oral delivery of hydrophilic macromolecules and reducing interindividual variability.

PubMed

AboulFotouh, Khaled; Allam, Ayat A; El-Badry, Mahmoud; El-Sayed, Ahmed M

2018-07-01

Self-emulsifying drug delivery systems (SEDDS) have been widely employed to improve the oral bioavailability of poorly soluble drugs. In the past few years, SEDDS were extensively investigated to overcome various barriers encountered in the oral delivery of hydrophilic macromolecules (e.g., protein/peptide therapeutics and plasmid DNA (pDNA)), as well as in lowering the effect of food on drugs' bioavailability. However, the main mechanism(s) by which SEDDS could achieve such promising effects remains not fully understood. This review summarizes the recent progress in the use of SEDDS for protecting protein therapeutics and/or pDNA against enzymatic degradation and increasing the oral bioavailability of various drug substances regardless of the dietary condition. Understanding the underlying mechanism(s) of such promising applications will aid in the future development of rationally designed SEDDS. Entrapment of hydrophilic macromolecules in the oil phase of the formed emulsion is critical for protection of the loaded cargoes against enzymatic degradation and the enhancement of oral bioavailability. On the other hand, drug administration as a preconcentrated solution in the SEDDS preconcentrate allows the process of drug absorption to occur independently of the dietary condition, and thus reducing interindividual variability that results from concomitant food intake. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of solid self-emulsifying drug delivery system (SEDDS) I: use of poloxamer 188 as both solidifying and emulsifying agent for lipids.

PubMed

Shah, Ankita V; Serajuddin, Abu T M

2012-10-01

To develop solid self-emulsifying drug delivery systems (SEDDS) for lipids using poloxamer 188 as both solidifying and emulsifying agents. Mixtures of various lipids with poloxamer 188 and PEG 8000 were prepared at ~75°C. The molten mixtures, with and without dissolved drugs (fenofibrate and probucol), were then cooled to room temperature. When solids formed, they were characterized by powder XRD, DSC, microscopy using cross-polarization and confocal fluorescence techniques, dispersion test in water and particle size analysis of dispersions. When mixed with poloxamer 188 or PEG 8000, lipids consisting of monoesters of fatty acids with glycerol or propylene glycol formed solid systems, but not di- and tri-esters, which showed phase separation. Added to water, the solid systems containing poloxamer 188 started to disperse in water forming oil globules of 200-600 nm. No emulsification of lipids was observed from solids containing PEG 8000, indicating that the surfactant property of poloxamer 188 was responsible for emulsification. Powder XRD, DSC and microscopic examination revealed that poloxamer 188 and PEG 8000 maintained their crystallinity in solid systems, while the lipids were interspersed in between crystalline regions. The drug remained solubilized in the lipid phase. A novel solid SEDDS is developed where the drug can be solubilized in liquid lipids and then the lipidic solution can be converted to solid mass by dispersing into the microstructure of poloxamer 188.

Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle.

PubMed

Helbling, Ignacio M; Busatto, Carlos A; Fioramonti, Silvana A; Pesoa, Juan I; Santiago, Liliana; Estenoz, Diana A; Luna, Julio A

2018-02-20

Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5-8 days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system. Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data. Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69-75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained. The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.

Dendrimersomes Exhibit Lamellar-to-Sponge Phase Transitions.

PubMed

Wilner, Samantha E; Xiao, Qi; Graber, Zachary T; Sherman, Samuel E; Percec, Virgil; Baumgart, Tobias

2018-05-15

Lamellar to nonlamellar membrane shape transitions play essential roles in key cellular processes, such as membrane fusion and fission, and occur in response to external stimuli, including drug treatment and heat. A subset of these transitions can be modeled by means of thermally inducible amphiphile assemblies. We previously reported on mixtures of hydrogenated, fluorinated, and hybrid Janus dendrimers (JDs) that self-assemble into complex dendrimersomes (DMSs), including dumbbells, and serve as promising models for understanding the complexity of biological membranes. Here we show, by means of a variety of complementary techniques, that DMSs formed by single JDs or by mixtures of JDs undergo a thermally induced lamellar-to-sponge transition. Consistent with the formation of a three-dimensional bilayer network, we show that DMSs become more permeable to water-soluble fluorophores after transitioning to the sponge phase. These DMSs may be useful not only in modeling isotropic membrane rearrangements of biological systems but also in drug delivery since nonlamellar delivery vehicles can promote endosomal disruption and cargo release.

Gelatin Particle-Stabilized High-Internal Phase Emulsions for Use in Oral Delivery Systems: Protection Effect and in Vitro Digestion Study.

PubMed

Tan, Huan; Zhao, Lifeng; Tian, Sisi; Wen, Hui; Gou, Xiaojun; Ngai, To

2017-02-01

The potential application of Pickering high-internal phase emulsions (HIPEs) in the food and pharmaceutical industries has yet to be fully developed. Herein, we synthesized fairly monodisperse, nontoxic, autofluorescent gelatin particles for use as sole stabilizers for fabricating oil-in-water (O/W) HIPEs in an effort to improve the protection and bioaccessibility of entrapped β-carotene. Our results showed that the concentration of gelatin particles determined the formation, microstructure, droplet size distribution, and digestion profile of the HIPEs. For storage stability, the retention of β-carotene in HIPEs was significantly higher than in dispersion in bulk oil, even after storage for 27 days. In addition, in vitro digestion experiments indicated that the bioaccessibility of β-carotene was improved 5-fold in HIPEs. This study will help establish a correlation between the physicochemical properties of gelatin particle-stabilized HIPEs with their applications in the oral delivery of bioactive nutraceuticals.

Identification and assessment of permeability enhancing vehicles for transdermal delivery of glucosamine hydrochloride.

PubMed

Han, In Hee; Choi, Sung-Up; Nam, Dae Young; Park, Young Mi; Kang, Myung Joo; Kang, Kyoung Hoon; Kim, Yong Min; Bae, Gunho; Oh, Il Young; Park, Jong Hyeok; Ye, Jin Soo; Choi, Yoon Bae; Kim, Duk Ki; Lee, Jaehwi; Choi, Young Wook

2010-02-01

As an initial step to develop the transdermal delivery system of glucosamine hydrochloride (GL-HCl), the permeation study across the rat skin in vitro was performed to identify the most efficient vehicle with regard to the ability to deliver GL-HCl transdermally. The GL-HCl formulations such as o/w cream, liposome suspension, liposomal gel, and liquid crystalline vehicles were prepared and compared for transdermal flux of GL-HCl. The liquid crystalline vehicles were more effective in increasing the skin permeation of GL-HCl than o/w cream and liposomal vehicles. Of the liquid crystalline vehicles tested, the permeation enhancing ability of the cubic phase was greater than that of the hexagonal phase when the nanoparticle dispersion was used. The skin permeation enhancing ability of the cubic nanoparticles for GL-HCl was further increased by employing both oleic acid and polyethylene glycol 200. Therefore, the cubic liquid crystalline nanodispersion containing oleic acid and PEG 200 can provide a possibility of clinical application of transdermal GL-HCl.

Drug "Pent-Up" in Hollow Magnetic Prussian Blue Nanoparticles for NIR-Induced Chemo-Photothermal Tumor Therapy with Trimodal Imaging.

PubMed

Li, Jinghua; Zhang, Fengshou; Hu, Zhigang; Song, Weidong; Li, Guangda; Liang, Gaofeng; Zhou, Jun; Li, Ke; Cao, Yang; Luo, Zhong; Cai, Kaiyong

2017-07-01

The study reports a biocompatible smart drug delivery system based on a doxorubicin (DOX) blending phase-change material of 1-pentadecanol loaded hollow magnetic Prussian blue nanoparticles, resulting in HMNP-PB@Pent@DOX. The system possesses concentration-dependent high thermogenesis (>50 °C) when applying a near-infrared (NIR) laser irradiation only for 5 min. Furthermore, the system realizes near "zero release" of drug and is efficiently triggered by NIR for drug delivery in an "on" and "off" manner, thus inducing cell apoptosis in vitro and in vivo. Moreover, the system clearly indicates tumor site with trimodal imaging of magnetic resonance imaging, photoacoustic tomography imaging, and infrared thermal imaging. Furthermore, the system achieves efficient chemo-photothermal combined tumor therapy in vivo with 808 nm laser irradiation for 5 min at 1.2 W cm -2 , revealing the good tumor inhibition effect comparing with those of chemotherapy or photothermal therapy alone. The system is also confirmed to be biocompatible in regard to the mortality rate. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimized delivery radiological reports: applying Six Sigma methodology to a radiology department.

PubMed

Cavagna, Enrico; Berletti, Riccardo; Schiavon, Francesco; Scarsi, Barbara; Barbato, Giuseppe

2003-03-01

To optimise the process of reporting and delivering radiological examinations with a view to achieving 100% service delivery within 72 hours to outpatients and 36 hours to inpatients. To this end, we used the Six Sigma method which adopts a systematic approach and rigorous statistical analysis to analyse and improve processes, by reducing variability and minimising errors. More specifically, our study focused on the process of radiological report creation, from the end of the examination to the time when the report is made available to the patient, to examine the bottlenecks and identify the measures to be taken to improve the process. Six Sigma uses a five-step problem-solving process called DMAIC, an acronym for Define, Measure, Analyze, Improve and Control. The first step is to define the problem and the elements crucial to quality, in terms of Total Quality Control. Next, the situation is analysed to identify the root causes of the problem and determine which of these is most influential. The situation is then improved by implementing change. Finally, to make sure that the change is long-lasting, measures are taken to sustain the improvements and obtain long-term control. In our case we analysed all of the phases the report passes through before reaching the user, and studied the impact of voice-recognition reporting on the speed of the report creation process. Analysis of the information collected showed that the tools available for report creation (dictaphone, voice-recognition system) and the transport of films and reports were the two critical elements on which to focus our efforts. Of all the phases making up the process, reporting (from end of examination to end of reporting) and distribution (from the report available to administrative staff to report available to the patient) account for 90% of process variability (73% and 17%, respectively). We further found that the reports dictated into a voice-recognition reporting system are delivered in 45 hours (median), whereas those dictated using a dictaphone take 96 hours: voice-recognition reporting systems therefore improve performance by 50 hours. Unfortunately, 38% of our reports are delivered within longer timeframes than the 72h for outpatients and 36h for inpatients agreed with the service users. Reports for inpatients have much faster delivery times and lower variability, as 95% of these examinations are reported using voice-recognition reporting (as a result of the greater sensitivity of physicians to the problem of inpatient waiting times). For conventional radiology examinations, numerically greater than CT or MRI, there is a stronger tendency to use the dictaphone which allows for faster dictation as it is unburdened by administrative tasks such as entering examination codes, correcting errors, etc. Freelance status has no impact on report delivery times, service delivery being the same as in the institutional setting. The subprocess of reporting is strongly affected by the choice of reporting method (voice-recognition system or dictaphone), whereas report delivery is affected by the individual's behaviour patterns and ultimately by habits generated by the lack of a clearly charted process (lack of synchronisation among the various phases), and therefore potentially avoidable. The analytical study of the various phases of examination reporting, from writing to delivery, allowed us to identify the process bottlenecks and take corrective measures. Regardless of imaging modality and individual physician, examination reporting consistently takes longer when a dictaphone is used instead of a voice-recognition reporting system, as this makes the process more complex. To improve the two critical subprocesses whilst maintaining constant resources, a first step is to abandon the dictaphone in favour of the voice-recognition system. In addition, we are experimenting other measures to improve the collection and sorting of examinations and the delivery of reports: the technical staff take the films from the examination rooms to the reporting rooms three times a day; the radiologists collect their examinations and prepare the reports, possibly on the same day; the radiologists leave their signed reports on the table in the central reporting room; the administrative staff collect the signed reports three times a day in the morning and afternoon to be able to deliver them on the same day. This project has allowed us to become familiar with the principles of total quality, to better understand our internal processes and to take effective measures to optimise them. This has resulted in enhanced satisfaction of all the department staff and has laid the grounds for further measures in the future.

Implementation of a web-based medication tracking system in a large academic medical center.

PubMed

Calabrese, Sam V; Williams, Jonathan P

2012-10-01

Pharmacy workflow efficiencies achieved through the use of an electronic medication-tracking system are described. Medication dispensing turnaround times at the inpatient pharmacy of a large hospital were evaluated before and after transition from manual medication tracking to a Web-based tracking process involving sequential bar-code scanning and real-time monitoring of medication status. The transition was carried out in three phases: (1) a workflow analysis, including the identification of optimal points for medication scanning with hand-held wireless devices, (2) the phased implementation of an automated solution and associated hardware at a central dispensing pharmacy and three satellite locations, and (3) postimplementation data collection to evaluate the impact of the new tracking system and areas for improvement. Relative to the manual tracking method, electronic medication tracking allowed the capture of far more data points, enabling the pharmacy team to delineate the time required for each step of the medication dispensing process and to identify the steps most likely to involve delays. A comparison of baseline and postimplementation data showed substantial reductions in overall medication turnaround times with the use of the Web-based tracking system (time reductions of 45% and 22% at the central and satellite sites, respectively). In addition to more accurate projections and documentation of turnaround times, the Web-based tracking system has facilitated quality-improvement initiatives. Implementation of an electronic tracking system for monitoring the delivery of medications provided a comprehensive mechanism for calculating turnaround times and allowed the pharmacy to identify bottlenecks within the medication distribution system. Altering processes removed these bottlenecks and decreased delivery turnaround times.

Safety and toxicity of nanomaterials for ocular drug delivery applications.

PubMed

Mehra, Neelesh K; Cai, Defu; Kuo, Lih; Hein, Travis; Palakurthi, Srinath

2016-09-01

Multifunctional nanomaterials are rapidly emerging for ophthalmic delivery of therapeutics to facilitate safe and effective targeting with improved patient compliance. Because of their extremely high area to volume ratio, nanomaterials often have physicochemical properties that are different from those of their larger counterparts. There exists a complex relationship between the physicochemical properties (composition, size, shape, charge, roughness, and porosity) of the nanomaterials and their interaction with the biological system. The eye is a very sensitive accessible organ and is subjected to intended and unintended exposure to nanomaterials. Currently, various ophthalmic formulations are available in the market, while some are underway in preclinical and clinical phases. However, the data on safety, efficacy, and toxicology of these advanced nanomaterials for ocular drug delivery are sparse. Focus of the present review is to provide a comprehensive report on the safety, biocompatibility and toxicities of nanomaterials in the eye.

SIMULATION AND VISUALIZATION OF FLOW PATTERN IN MICROARRAYS FOR LIQUID PHASE OLIGONUCLEOTIDE AND PEPTIDE SYNTHESIS

PubMed Central

O-Charoen, Sirimon; Srivannavit, Onnop; Gulari, Erdogan

2008-01-01

Microfluidic microarrays have been developed for economical and rapid parallel synthesis of oligonucleotide and peptide libraries. For a synthesis system to be reproducible and uniform, it is crucial to have a uniform reagent delivery throughout the system. Computational fluid dynamics (CFD) is used to model and simulate the microfluidic microarrays to study geometrical effects on flow patterns. By proper design geometry, flow uniformity could be obtained in every microreactor in the microarrays. PMID:17480053

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

KIRKBRIDE, R.A.

The Tank Waste Remediation System Operation and Utilization Plan updates the operating scenario and plans for the delivery of feed to BNFL Inc., retrieval of waste from single-shell tanks, and the overall process flowsheets for Phases I and II of the privatization of the Tank Waste Remediation System. The plans and flowsheets are updated with the most recent tank-by-tank inventory and sludge washing data. Sensitivity cases were run to evaluate the impact or benefits of proposed changes to the BNFL Inc. contract and to evaluate a risk-based SST retrieval strategy.

RN Diabetes Virtual Case Management: A New Model for Providing Chronic Care Management.

PubMed

Brown, Nancy N; Carrara, Barbara E; Watts, Sharon A; Lucatorto, Michelle A

2016-01-01

The U.S. chronic disease health care system has substantial gaps in delivery of services. New models of care change traditional delivery of care and explore new settings for care. This article describes a new model of diabetes chronic care delivery: nurse-delivered care that includes protocol-based insulin titration and patient education delivered solely in a virtual environment. In phase 1, the clinical outcome of time to achievement of glycated hemoglobin (A(1C)) goals (P < .001; 95% confidence interval, 1.68-2.24) was significantly improved by registered nurse (RN) standing order intervention (n = 24) as compared with historical controls (n = 28). In phase 2, patients who were referred to an RN-managed insulin titration protocol with individualized A(1C) goals had a significant (P < .001; 95% confidence interval, 1.680-2.242) reduction in results from a mean of 9.6% at baseline to 7.7% at completion. Average patient age was 66 years, with a mean duration of 11 years diagnosed with diabetes. Safety was demonstrated by the absence of hypoglycemia related to RN protocol adjustment. There were no admissions or emergency room (ER) visits for hypoglycemia. This study demonstrates safety and efficacy of RN virtual chronic disease management for an older population of patients with long-standing diabetes.

A Two-Phase Model for Trade Matching and Price Setting in Double Auction Water Markets

NASA Astrophysics Data System (ADS)

Xu, Tingting; Zheng, Hang; Zhao, Jianshi; Liu, Yicheng; Tang, Pingzhong; Yang, Y. C. Ethan; Wang, Zhongjing

2018-04-01

Delivery in water markets is generally operated by agencies through channel systems, which imposes physical and institutional market constraints. Many water markets allow water users to post selling and buying requests on a board. However, water users may not be able to choose efficiently when the information (including the constraints) becomes complex. This study proposes an innovative two-phase model to address this problem based on practical experience in China. The first phase seeks and determines the optimal assignment that maximizes the incremental improvement of the system's social welfare according to the bids and asks in the water market. The second phase sets appropriate prices under constraints. Applying this model to China's Xiying Irrigation District shows that it can improve social welfare more than the current "pool exchange" method can. Within the second phase, we evaluate three objective functions (minimum variance, threshold-based balance, and two-sided balance), which represent different managerial goals. The threshold-based balance function should be preferred by most users, while the two-sided balance should be preferred by players who post extreme prices.

Linear feature extraction from radar imagery: SBIR (Small Business Innovative Research) phase 2, option 1

NASA Astrophysics Data System (ADS)

Conner, Gary D.; Milgram, David L.; Lawton, Daryl T.; McConnell, Christopher C.

1988-04-01

The goal of this effort is to develop and demonstrate prototype processing capabilities for a knowledge-based system to automatically extract and analyze linear features from synthetic aperture radar (SAR) imagery. This effort constitutes Phase 2 funding through the Defense Small Business Innovative Research (SBIR) Program. Previous work examined the feasibility of the technology issues involved in the development of an automatedlinear feature extraction system. This Option 1 Final Report documents this examination and the technologies involved in automating this image understanding task. In particular, it reports on a major software delivery containing an image processing algorithmic base, a perceptual structures manipulation package, a preliminary hypothesis management framework and an enhanced user interface.

Pilot vehicle interface on the advanced fighter technology integration F-16

NASA Technical Reports Server (NTRS)

Dana, W. H.; Smith, W. B.; Howard, J. D.

1986-01-01

This paper focuses on the work load aspects of the pilot vehicle interface in regard to the new technologies tested during AMAS Phase II. Subjects discussed in this paper include: a wide field-of-view head-up display; automated maneuvering attack system/sensor tracker system; master modes that configure flight controls and mission avionics; a modified helmet mounted sight; improved multifunction display capability; a voice interactive command system; ride qualities during automated weapon delivery; a color moving map; an advanced digital map display; and a g-induced loss-of-consciousness and spatial disorientation autorecovery system.

Advanced fighter technology integration (AFTI)/F-16 Automated Maneuvering Attack System final flight test results

NASA Technical Reports Server (NTRS)

Dowden, Donald J.; Bessette, Denis E.

1987-01-01

The AFTI F-16 Automated Maneuvering Attack System has undergone developmental and demonstration flight testing over a total of 347.3 flying hours in 237 sorties. The emphasis of this phase of the flight test program was on the development of automated guidance and control systems for air-to-air and air-to-ground weapons delivery, using a digital flight control system, dual avionics multiplex buses, an advanced FLIR sensor with laser ranger, integrated flight/fire-control software, advanced cockpit display and controls, and modified core Multinational Stage Improvement Program avionics.

Clinical Opinion: "Doing Something" About the Cesarean Delivery Rate.

PubMed

Clark, S L; Garite, T J; Hamilton, E J; Belfort, M A; Hankins, G D

2018-05-04

There is a general consensus that the cesarean delivery rate in the U.S. is too high, and that practice patterns of obstetricians are largely to blame for this situation. In reality, the U.S. cesarean delivery rate is the result of 3 forces largely beyond the control of the practicing clinician: patient expectations and misconceptions regarding the safety of labor, the medical-legal system, and limitations in technology. Efforts to "do something" about the cesarean delivery rate by promulgating practice directives which are marginally evidence-based or influenced by social pressures are both ineffective and potentially harmful. We examine both the recent ACOG/SMFM Care Consensus Statement "Safe Prevention of Primary Cesarean Delivery" document and the various iterations of the ACOG guidelines for vaginal birth after cesarean delivery in this context. Adherence to arbitrary time limits for active phase or second stage arrest without incorporating other clinical factors into the decision making process is unwise. In a similar manner, ever-changing practice standards for vaginal birth after cesarean driven by factors other than changing data are unlikely to be effective in lowering the cesarean delivery rate. Whether too high or too low, the current U.S. cesarean delivery rate is the expected result of the unique demographic, geographic and social forces driving it and is unlikely to change significantly given the limitations of current technology to otherwise satisfy the demands of these forces. Copyright © 2018 Elsevier Inc. All rights reserved.

Space Fence PDR Concept Development Phase

NASA Astrophysics Data System (ADS)

Haines, L.; Phu, P.

2011-09-01

The Space Fence, a major Air Force acquisition program, will become the dominant low-earth orbit uncued sensor in the space surveillance network (SSN). Its primary objective is to provide a 24/7 un-cued capability to find, fix, and track small objects in low earth orbit to include emerging and evolving threats, as well as the rapidly growing population of orbital debris. Composed of up to two geographically dispersed large-scale S-band phased array radars, this new system-of-systems concept will provide comprehensive Space Situational Awareness through net-centric operations and integrated decision support. Additionally, this program will facilitate cost saving force structure changes in the SSN, specifically including the decommissioning of very-high frequency VHF Air Force Space Surveillance System (AFSSS). The Space Fence Program Office entered a Preliminary Design Review (PDR) concept development phase in January 2011 to achieve the delivery of the Initial Operational Capability (IOC) expected in FY17. Two contractors were awarded to perform preliminary system design, conduct radar performance analyses and evaluations, and develop a functional PDR radar system prototype. The key objectives for the Phase A PDR effort are to reduce Space Fence total program technical, cost, schedule, and performance risk. The overall program objective is to achieve a preliminary design that demonstrates sufficient technical and manufacturing maturity and that represents a low risk, affordable approach to meet the Space Fence Technical Requirements Document (TRD) requirements for the final development and production phase to begin in 3QFY12. This paper provides an overview of the revised Space Fence program acquisition strategy for the Phase-A PDR phase to IOC, the overall program milestones and major technical efforts. In addition, the key system trade studies and modeling/simulation efforts undertaken during the System Design Requirement (SDR) phase to address and mitigate technical challenges of the Space Fence System will also be discussed. Examples include radar system optimization studies, modeling and simulation for system performance assessment, investigation of innovative Astrodynamics algorithms for initial orbit determination and observation correlation.

Optimized formulation of solid self-microemulsifying sirolimus delivery systems

PubMed Central

Cho, Wonkyung; Kim, Min-Soo; Kim, Jeong-Soo; Park, Junsung; Park, Hee Jun; Cha, Kwang-Ho; Park, Jeong-Sook; Hwang, Sung-Joo

2013-01-01

Background The aim of this study was to develop an optimized solid self-microemulsifying drug delivery system (SMEDDS) formulation for sirolimus to enhance its solubility, stability, and bioavailability. Methods Excipients used for enhancing the solubility and stability of sirolimus were screened. A phase-separation test, visual observation for emulsifying efficiency, and droplet size analysis were performed. Ternary phase diagrams were constructed to optimize the liquid SMEDDS formulation. The selected liquid SMEDDS formulations were prepared into solid form. The dissolution profiles and pharmacokinetic profiles in rats were analyzed. Results In the results of the oil and cosolvent screening studies, Capryol™ Propylene glycol monocapry late (PGMC) and glycofurol exhibited the highest solubility of all oils and cosolvents, respectively. In the surfactant screening test, D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was determined to be the most effective stabilizer of sirolimus in pH 1.2 simulated gastric fluids. The optimal formulation determined by the construction of ternary phase diagrams was the T32 (Capryol™ PGMC:glycofurol:vitamin E TPGS = 30:30:40 weight ratio) formulation with a mean droplet size of 108.2 ± 11.4 nm. The solid SMEDDS formulations were prepared with Sucroester 15 and mannitol. The droplet size of the reconstituted solid SMEDDS showed no significant difference compared with the liquid SMEDDS. In the dissolution study, the release amounts of sirolimus from the SMEDDS formulation were significantly higher than the raw sirolimus powder. In addition, the solid SMEDDS formulation was in a more stable state than liquid SMEDDS in pH 1.2 simulated gastric fluids. The results of the pharmacokinetic study indicate that the SMEDDS formulation shows significantly greater bioavailability than the raw sirolimus powder or commercial product (Rapamune® oral solution). Conclusion The results of this study suggest the potential use of a solid SMEDDS formulation for the delivery of poorly water-soluble drugs, such as sirolimus, through oral administration. PMID:23641156

Peroxotitanates for Biodelivery of Metals

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

Hobbs, David; Elvington, M.

2009-02-11

Metal-based drugs are largely undeveloped in pharmacology. One limiting factor is the systemic toxicity of metal-based compounds. A solid-phase, sequestratable delivery agent for local delivery of metals could reduce systemic toxicity, facilitating new drug development in this nascent area. Amorphous peroxotitanates (APT) are ion exchange materials with high affinity for several heavy metal ions, and have been proposed to deliver or sequester metal ions in biological contexts. In the current study, we tested a hypothesis that APT are able to deliver metals or metal compounds to cells. We exposed fibroblasts (L929) or monocytes (THP1) to metal-APT materials for 72 hmore » in vitro, then measured cellular mitochondrial activity (SDH-MTT method) to assess the biological impact of the metal-APT materials vs. metals or APT alone. APT alone did not significantly affect cellular mitochondrial activity, but all metal-APT materials suppressed the mitochondrial activity of fibroblasts (by 30-65% of controls). The concentration of metal-APT materials required to suppress cellular mitochondrial activity was below that required for metals alone, suggesting that simple extracellular release of the metals from the metal-APT materials was not the primary mechanism of mitochondrial suppression. In contrast to fibroblasts, no metal-APT material had a measurable effect on THP1 monocyte mitochondrial activity, despite potent suppression by metals alone. This latter result suggested that 'biodelivery' by metal-APT materials may be cell type-specific. Therefore, it appears that APT are plausible solid phase delivery agents of metals or metal compounds to some types of cells for potential therapeutic effect.« less

Self-assembled liquid crystalline nanoparticles as a novel ophthalmic delivery system for dexamethasone: Improving preocular retention and ocular bioavailability.

PubMed

Gan, Li; Han, Shun; Shen, Jinqiu; Zhu, Jiabi; Zhu, Chunliu; Zhang, Xinxin; Gan, Yong

2010-08-30

The object of this study was to design novel self-assembled liquid crystalline nanoparticles (cubosomes) as an ophthalmic delivery system for dexamethasone (DEX) to improve its preocular retention and ocular bioavailability. DEX cubosome particles were produced by fragmenting a cubic crystalline phase of monoolein and water in the presence of stabilizer Poloxamer 407. Small angle X-ray diffraction (SAXR) profiles revealed its internal structure as Pn3m space group, indicating the diamond cubic phase. In vitro, the apparent permeability coefficient of DEX administered in cubosomes exhibited a 4.5-fold (F1) and 3.5-fold (F2) increase compared to that of Dex-Na phosphate eye drops. Preocular retention studies revealed that the retention of cubosomes was significantly longer than that of solution and carbopol gel, with AUC(0-->180min) of Rh B cubosomes being 2-3-fold higher than that of the other two formulations. In vivo pharmacokinetics in aqueous humor was evaluated by microdialysis, which indicated a 1.8-fold (F1) increase in AUC(0-->240min) of DEX administered in cubosomes relative to that of Dex-Na phosphate eye drops, with about an 8-fold increase compared to that of DEX suspension. Corneal cross-sections after incubation with DEX cubosomes demonstrated an unaffected corneal structure and tissue integrity, which indicated the good biocompatibility of DEX cubosomes. In conclusion, self-assembled liquid crystalline nanoparticles might represent a promising vehicle for effective ocular drug delivery. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

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.

Sex and menstrual cycle effects on chronic oral cocaine self-administration in rhesus monkeys: Effects of a nondrug alternative reward.

PubMed

Carroll, Marilyn E; Collins, Molly; Kohl, Emily A; Johnson, Seth; Dougen, Ben

2016-08-01

In previous studies, female monkeys self-administered more oral phencyclidine (PCP) than males, and PCP intake differed by phase of menstrual cycle. The purpose of this study was to examine sex and hormonal influences on oral cocaine self-administration in male and female rhesus monkeys in the follicular vs. luteal phases of the menstrual cycle, with concurrent access to an alternative nondrug reward, saccharin (SACC) vs. water. Concurrent access to cocaine (0.2, 0.4, and 0.8 mg/ml) and SACC or water was available from two drinking spouts under concurrent fixed-ratio (FR) 2, 4, and 8 schedules during daily 3-h sessions. Cocaine deliveries were similar in males and females in the females' luteal phase, but cocaine deliveries were higher in females during the follicular phase than the luteal phase and compared to males. When SACC was available, cocaine deliveries were reduced in females in the follicular phase of the cycle, and cocaine intake (mg/kg) was reduced in males and in females' follicular and luteal phases. Access to concurrent SACC (vs. water) reduced cocaine intake (mg/kg) in males and in females during both menstrual phases, and the magnitude of the reduction in cocaine intake was greatest during the females' follicular phase. Thus, a nondrug alternative reward, SACC, is a viable alternative treatment for reducing cocaine's rewarding effects on male and female monkeys, and reductions in cocaine seeking were optimal in the females' luteal phase.

A margin model to account for respiration-induced tumour motion and its variability

NASA Astrophysics Data System (ADS)

Coolens, Catherine; Webb, Steve; Shirato, H.; Nishioka, K.; Evans, Phil M.

2008-08-01

In order to reduce the sensitivity of radiotherapy treatments to organ motion, compensation methods are being investigated such as gating of treatment delivery, tracking of tumour position, 4D scanning and planning of the treatment, etc. An outstanding problem that would occur with all these methods is the assumption that breathing motion is reproducible throughout the planning and delivery process of treatment. This is obviously not a realistic assumption and is one that will introduce errors. A dynamic internal margin model (DIM) is presented that is designed to follow the tumour trajectory and account for the variability in respiratory motion. The model statistically describes the variation of the breathing cycle over time, i.e. the uncertainty in motion amplitude and phase reproducibility, in a polar coordinate system from which margins can be derived. This allows accounting for an additional gating window parameter for gated treatment delivery as well as minimizing the area of normal tissue irradiated. The model was illustrated with abdominal motion for a patient with liver cancer and tested with internal 3D lung tumour trajectories. The results confirm that the respiratory phases around exhale are most reproducible and have the smallest variation in motion amplitude and phase (approximately 2 mm). More importantly, the margin area covering normal tissue is significantly reduced by using trajectory-specific margins (as opposed to conventional margins) as the angular component is by far the largest contributor to the margin area. The statistical approach to margin calculation, in addition, offers the possibility for advanced online verification and updating of breathing variation as more data become available.

Ethosomes and Transfersomes: Principles, Perspectives and Practices.

PubMed

Garg, Varun; Singh, Harmanpreet; Bimbrawh, Sneha; Singh, Sachin Kumar; Gulati, Monica; Vaidya, Yogyata; Kaur, Prabhjot

2017-01-01

The success story of liposomes in the treatment of systemic infectious diseases and various carcinomas lead the scientists to the innovation of elastic vesicles to achieve similar success through transdermal route. In this direction, ethosomes and transfersomes were developed with the objective to design the vesicles that could pass through the skin. However, there is a lack of systematic review outlining the principles, method of preparation, latest advancement and applications of ethosomes and transfersomes. This review covers various aspects that would be helpful to scientists in understanding advantages of these vesicular systems and designing a unique nano vesicular delivery system. Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of principle of these vesicular delivery systems, composition, mechanism of actions, preparation techniques, methods for their characterization and their application. A total of 182 papers including both, research and review articles, were included in this review in order to make the article comprehensive and readily understandable. The mechanism of action and composition of ethosomes and transfersomes was extensively discussed. Various methods of preparation such as, rotary film evaporation method, reverse phase evaporation method, vortex/ sonication method, ethanol injection method, freeze thaw methods, along with their advantages has been discussed. It was also discussed that both these elastic nanocarriers offer unique advantages of ferrying the drug across membranes, sustaining drug release as well as protecting the encapsulated bio actives from external environment. The enhanced bioavailability and skin penetration of ethosomes as compared to conventional vesicular delivery systems is attributed to the presence of ethanol in the bilayers while that for transfersomes accrues due to their elasticity along with their ability to retain their shape because of the presence of edge activators. Successful delivery of synthetic drugs as well as phytomedicines has been extensively reported through these vesicles. Though these vesicular systems offer a good potential for rational drug delivery, a thoughtfully designed process is required to optimize the process variables involved. Industrial scale production of efficacious, safe, cost effective and stable formulations of both these delivery systems appears to be a pre-requisite to ensure their utility as the trans-dermal vehicles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Investigation of Phase Transition-Based Tethered Systems for Small Body Sample Capture

NASA Technical Reports Server (NTRS)

Quadrelli, Marco; Backes, Paul; Wilkie, Keats; Giersch, Lou; Quijano, Ubaldo; Scharf, Daniel; Mukherjee, Rudranarayan

2009-01-01

This paper summarizes the modeling, simulation, and testing work related to the development of technology to investigate the potential that shape memory actuation has to provide mechanically simple and affordable solutions for delivering assets to a surface and for sample capture and possible return to Earth. We investigate the structural dynamics and controllability aspects of an adaptive beam carrying an end-effector which, by changing equilibrium phases is able to actively decouple the end-effector dynamics from the spacecraft dynamics during the surface contact phase. Asset delivery and sample capture and return are at the heart of several emerging potential missions to small bodies, such as asteroids and comets, and to the surface of large bodies, such as Titan.

Modeling and Testing of Phase Transition-Based Deployable Systems for Small Body Sample Capture

NASA Technical Reports Server (NTRS)

Quadrelli, Marco; Backes, Paul; Wilkie, Keats; Giersch, Lou; Quijano, Ubaldo; Keim, Jason; Mukherjee, Rudranarayan

2009-01-01

This paper summarizes the modeling, simulation, and testing work related to the development of technology to investigate the potential that shape memory actuation has to provide mechanically simple and affordable solutions for delivering assets to a surface and for sample capture and return. We investigate the structural dynamics and controllability aspects of an adaptive beam carrying an end-effector which, by changing equilibrium phases is able to actively decouple the end-effector dynamics from the spacecraft dynamics during the surface contact phase. Asset delivery and sample capture and return are at the heart of several emerging potential missions to small bodies, such as asteroids and comets, and to the surface of large bodies, such as Titan.

Omega-3 fatty acids incorporated colloidal systems for the delivery of Angelica gigas Nakai extract.

PubMed

Lee, Jeong-Jun; Park, Ju-Hwan; Lee, Jae-Young; Jeong, Jae Young; Lee, Song Yi; Yoon, In-Soo; Kang, Wie-Soo; Kim, Dae-Duk; Cho, Hyun-Jong

2016-04-01

Omega-3 (ω-3) fish oil-enriched colloidal systems were developed for the oral delivery of Angelica gigas Nakai (AGN) extract (ext). By constructing a pseudo-ternary phase diagram, the composition of oil-in-water (o/w) microemulsion (ME) systems based on ω-3 (oil), Labrasol (surfactant), and water was determined. AGN ext was dissolved into the ME system and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was added to the ME formulation in order to enhance the mucosal absorption of the pharmacologically active ingredients in the AGN ext. The droplet size of AGN-loaded MEs was 205-277 nm and their morphology was spherical. The release of major components of AGN, decursin (D) and decursinol angelate (DA), from ME formulations in pH 1.2 and 6.8 buffers was significantly greater (P<0.05) than that from the AGN suspension group. The pharmacokinetic properties of AGN-loaded MEs in rats were evaluated by measuring decursinol (DOH) concentrations in plasma after oral administration. TPGS-included ME (F2) resulted in significantly greater (P<0.05) systemic exposure of DOH than that with ME without TPGS (F1), AGN ext+TPGS, and AGN in suspension. Severe toxicity of F1 and F2 on the intestinal epithelium was not observed by histological staining. The colloidal carriers described herein are promising delivery systems for oral administration of AGN ext. Copyright © 2015 Elsevier B.V. All rights reserved.

Solid self-nanoemulsifying delivery systems as a platform technology for formulation of poorly soluble drugs.

PubMed

Bansal, Tripta; Mustafa, Gulam; Khan, Zeenat I; Ahmad, Farhaan J; Khar, Roop K; Talegaonkar, Sushama

2008-01-01

New drug discovery programs produce molecules with poor physico-chemical properties, making delivery of these molecules at the right proportion into the body a big challenge to the formulation scientist. The various options available to overcome the hurdle include solvent precipitation, micronisation/nanonization using high-pressure homogenization or jet milling, salt formation, use of microspheres, solid dispersions, cogrinding, complexation, and many others. Self-nanoemulsifying systems (SNES) form one of the most popular and commercially viable approaches for delivery of poorly soluble drugs exhibiting dissolution rate limited absorption, especially those belonging to the Biopharmaceutics Classification System II/IV. SNES are essentially an isotropic blend of oils, surfactants, and/or cosolvents that emulsify spontaneously to produce oil in water nanoemulsion when introduced into aqueous phase under gentle agitation. Conventional SNES consist of liquid forms filled in hard or soft gelatin capsules, which are least preferred due to leaching and leakage phenomenon, interaction with capsule shell components, handling difficulties, machinability, and stability problems. Solidification of these liquid systems to yield solid self-nanoemulsifying systems (SSNES) offer a possible solution to the mentioned complications, and that is why these systems have attracted wide attention. Other than the advantages and wide application of SSNEDS, the present paper focuses on formulation considerations, selection, and function of solidifying excipients; techniques of preparation; and case studies of drugs selected from different therapeutic categories. Developments in the techniques for in vitro evaluation of SSNEDS have also been discussed.

Design and evaluation of a dry coated drug delivery system with floating-pulsatile release.

PubMed

Zou, Hao; Jiang, Xuetao; Kong, Lingshan; Gao, Shen

2008-01-01

The objective of this work was to develop and evaluate a floating-pulsatile drug delivery system intended for chronopharmacotherapy. Floating-pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, we generated the system which consisted of three different parts, a core tablet, containing the active ingredient, an erodible outer shell and a top cover buoyant layer. The dry coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer which is responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with Methocel K4M, Carbopol 934P and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their buoyancy, dissolution and pharmacokinetic, as well gamma-scintigraphically. The results showed that a certain lag time before the drug released generally due to the erosion of the dry coated layer. Floating time was controlled by the quantity and composition of the buoyant layer. Both pharmacokinetic and gamma-scintigraphic data point out the capability of the system of prolonged residence of the tablets in the stomach and releasing drugs after a programmed lag time. (c) 2007 Wiley-Liss, Inc.

Design of liposomal colloidal systems for ocular delivery of ciprofloxacin

PubMed Central

Taha, Ehab I.; El-Anazi, Magda H.; El-Bagory, Ibrahim M.; Bayomi, Mohsen A.

2013-01-01

Ophthalmic drug bioavailability is limited due to protective mechanisms of the eye which require the design of a system to enhance ocular delivery. In this study several liposomal formulations containing ciprofloxacin (CPX) have been formulated using reverse phase evaporation technique with final dispersion of pH 7.4. Different types of phospholipids including Phosphatidylcholine, Dipalmitoylphosphatidylcholine and Dimyristoyl-sn-glycero-3-phosphocholine were utilized. The effect of formulation factors such as type of phospholipid, cholesterol content, incorporation of positively charging inducing agents and ultrasonication on the properties of the liposomal vesicles was studied. Bioavailability of selected liposomal formulations in rabbit eye aqueous humor has been investigated and compared with that of commercially available CPX eye drops (Ciprocin®). Pharmacokinetic parameters including Cmax, Tmax, elimination rate constant, t1/2, MRT and AUC0–∞, were determined. The investigated formulations showed more than three folds of improvement in CPX ocular bioavailability compared with the commercial product. PMID:25061409

Self-assembly formation of palm-based esters nano-emulsion: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Abdul Rahman, Mohd. Basyaruddin; Huan, Qiu-Yi; Tejo, Bimo A.; Basri, Mahiran; Salleh, Abu Bakar; Rahman, Raja Noor Zaliha Abdul

2009-10-01

Palm-oil esters (POEs) are unsaturated and non-ionic esters that can be prepared by enzymatic synthesis from palm oil. Their nano-emulsion properties possess great potential to act as drug carrier for transdermal drug delivery system. A ratio of 75:5:20 (water/POEs/Span20) was chosen from homogenous region in the phase diagram of our previous experimental work to undergo molecular dynamics simulation. A 15 ns molecular dynamics simulation of nano-emulsion system (water/POEs/Span20) was carried out using OPLS-AA force field. The aggregations of the oil and surfactant molecules are observed throughout the simulation. After 8 ns of simulation, the molecules start to aggregate to form one spherical micelle where the POEs molecules are surrounded by the non-ionic surfactant (Span20) molecules with an average size of 4.2 ± 0.05 nm. The size of the micelle and the ability of palm-based nano-emulsion to self-assemble suggest that this nano-emulsion can potentially use in transdermal drug delivery system.

Molecular nucleation mechanisms and control strategies for crystal polymorph selection.

PubMed

Van Driessche, Alexander E S; Van Gerven, Nani; Bomans, Paul H H; Joosten, Rick R M; Friedrich, Heiner; Gil-Carton, David; Sommerdijk, Nico A J M; Sleutel, Mike

2018-04-04

The formation of condensed (compacted) protein phases is associated with a wide range of human disorders, such as eye cataracts, amyotrophic lateral sclerosis, sickle cell anaemia and Alzheimer's disease. However, condensed protein phases have their uses: as crystals, they are harnessed by structural biologists to elucidate protein structures, or are used as delivery vehicles for pharmaceutical applications. The physiochemical properties of crystals can vary substantially between different forms or structures ('polymorphs') of the same macromolecule, and dictate their usability in a scientific or industrial context. To gain control over an emerging polymorph, one needs a molecular-level understanding of the pathways that lead to the various macroscopic states and of the mechanisms that govern pathway selection. However, it is still not clear how the embryonic seeds of a macromolecular phase are formed, or how these nuclei affect polymorph selection. Here we use time-resolved cryo-transmission electron microscopy to image the nucleation of crystals of the protein glucose isomerase, and to uncover at molecular resolution the nucleation pathways that lead to two crystalline states and one gelled state. We show that polymorph selection takes place at the earliest stages of structure formation and is based on specific building blocks for each space group. Moreover, we demonstrate control over the system by selectively forming desired polymorphs through site-directed mutagenesis, specifically tuning intermolecular bonding or gel seeding. Our results differ from the present picture of protein nucleation, in that we do not identify a metastable dense liquid as the precursor to the crystalline state. Rather, we observe nucleation events that are driven by oriented attachments between subcritical clusters that already exhibit a degree of crystallinity. These insights suggest ways of controlling macromolecular phase transitions, aiding the development of protein-based drug-delivery systems and macromolecular crystallography.

Molecular nucleation mechanisms and control strategies for crystal polymorph selection

NASA Astrophysics Data System (ADS)

van Driessche, Alexander E. S.; van Gerven, Nani; Bomans, Paul H. H.; Joosten, Rick R. M.; Friedrich, Heiner; Gil-Carton, David; Sommerdijk, Nico A. J. M.; Sleutel, Mike

2018-04-01

The formation of condensed (compacted) protein phases is associated with a wide range of human disorders, such as eye cataracts, amyotrophic lateral sclerosis, sickle cell anaemia and Alzheimer’s disease. However, condensed protein phases have their uses: as crystals, they are harnessed by structural biologists to elucidate protein structures, or are used as delivery vehicles for pharmaceutical applications. The physiochemical properties of crystals can vary substantially between different forms or structures (‘polymorphs’) of the same macromolecule, and dictate their usability in a scientific or industrial context. To gain control over an emerging polymorph, one needs a molecular-level understanding of the pathways that lead to the various macroscopic states and of the mechanisms that govern pathway selection. However, it is still not clear how the embryonic seeds of a macromolecular phase are formed, or how these nuclei affect polymorph selection. Here we use time-resolved cryo-transmission electron microscopy to image the nucleation of crystals of the protein glucose isomerase, and to uncover at molecular resolution the nucleation pathways that lead to two crystalline states and one gelled state. We show that polymorph selection takes place at the earliest stages of structure formation and is based on specific building blocks for each space group. Moreover, we demonstrate control over the system by selectively forming desired polymorphs through site-directed mutagenesis, specifically tuning intermolecular bonding or gel seeding. Our results differ from the present picture of protein nucleation, in that we do not identify a metastable dense liquid as the precursor to the crystalline state. Rather, we observe nucleation events that are driven by oriented attachments between subcritical clusters that already exhibit a degree of crystallinity. These insights suggest ways of controlling macromolecular phase transitions, aiding the development of protein-based drug-delivery systems and macromolecular crystallography.

pH-dependent Differential Scanning Calorimetry and Dynamic Light Scattering Studies of 21:0 PC and 18:0 PS Lipid Binary System

NASA Astrophysics Data System (ADS)

Ali, Rejwan

2010-03-01

Large unilamallar vesicle has been a model system to study many membrane functions. High Tg lipid systems offer many potential biomedical applications in lipid-based delivery applications. While the optimized vesicle functionalities are achieved by Polyethylene Glycol (PEG) polymer, modified PEG and other functional molecule incorporation, however, the host binary lipid system plays the pivotal role in pH-dependent phase transition based lipid vehicular methods. We have investigated a lipid binary system composed of 21:0 PC (1,2-dihenarachidoyl-sn-glycero-3-phosphocholine) and 18:0 PS(1,2-distearoyl-sn-glycero-3-phospho-L-serine). Preliminary studies implementing differential scanning calorimetry shows pH plays key role in temperature shift and thermotropic phase behavior of the binary system. While dynamic light scattering study shows lipid vesicle size is almost independent of pH changes. We will also present pH-dependent thermodynamic parameters to correlate underlying molecular mechanism in relevant pH-range.

Self-microemulsifying drug delivery system and nanoemulsion for enhancing aqueous miscibility of Alpinia galanga oil.

PubMed

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Müllertz, Anette; Rades, Thomas; Okonogi, Siriporn

2017-01-01

Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility limits its application particularly in aquatic animals. AGO has powerful activity on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows severe side effects on fish. The present study explores the development of self-microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were developed by means of high-energy emulsification. The mean droplet size of the best SMEDDS-AGO was 82 ± 0.5 nm whereas that of NE-AGO was 48 ± 1.6 nm. The anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio) was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found that the time of induction the fish to reach the surgical stage of anesthesia was dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In conclusion, SMEDDS and NE are promising delivery systems for AGO.

Self-microemulsifying drug delivery system and nanoemulsion for enhancing aqueous miscibility of Alpinia galanga oil

PubMed Central

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Müllertz, Anette; Rades, Thomas

2017-01-01

Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility limits its application particularly in aquatic animals. AGO has powerful activity on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows severe side effects on fish. The present study explores the development of self-microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were developed by means of high-energy emulsification. The mean droplet size of the best SMEDDS-AGO was 82 ± 0.5 nm whereas that of NE-AGO was 48 ± 1.6 nm. The anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio) was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found that the time of induction the fish to reach the surgical stage of anesthesia was dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In conclusion, SMEDDS and NE are promising delivery systems for AGO. PMID:29190663

Production methodologies of polymeric and hydrogel particles for drug delivery applications.

PubMed

Lima, Ana Catarina; Sher, Praveen; Mano, João F

2012-02-01

Polymeric particles are ideal vehicles for controlled delivery applications due to their ability to encapsulate a variety of substances, namely low- and high-molecular mass therapeutics, antigens or DNA. Micro and nano scale spherical materials have been developed as carriers for therapies, using appropriated methodologies, in order to achieve a prolonged and controlled drug administration. This paper reviews the methodologies used for the production of polymeric micro/nanoparticles. Emulsions, phase separation, spray drying, ionic gelation, polyelectrolyte complexation and supercritical fluids precipitation are all widely used processes for polymeric micro/nanoencapsulation. This paper also discusses the recent developments and patents reported in this field. Other less conventional methodologies are also described, such as the use of superhydrophobic substrates to produce hydrogel and polymeric particulate biomaterials. Polymeric drug delivery systems have gained increased importance due to the need for improving the efficiency and versatility of existing therapies. This allows the development of innovative concepts that could create more efficient systems, which in turn may address many healthcare needs worldwide. The existing methods to produce polymeric release systems have some critical drawbacks, which compromise the efficiency of these techniques. Improvements and development of new methodologies could be achieved by using multidisciplinary approaches and tools taken from other subjects, including nanotechnologies, biomimetics, tissue engineering, polymer science or microfluidics.

Chitosan-based thermosensitive hydrogel as a promising ocular drug delivery system: preparation, characterization, and in vivo evaluation.

PubMed

Chen, Xingwei; Li, Xinru; Zhou, Yanxia; Wang, Xiaoning; Zhang, Yanhui; Fan, Yating; Huang, Yanqing; Liu, Yan

2012-11-01

The purpose of this study was to evaluate the feasibility of in situ thermosensitive hydrogel based on chitosan in combination with disodium α-d-Glucose 1-phosphate (DGP) for ocular drug delivery system. Aqueous solution of chitosan/DGP underwent sol-gel transition as temperature increased which was flowing sol at room temperature and then turned into non-flowing hydrogel at physiological temperature. The properties of gels were characterized regarding gelation time, gelation temperature, and morphology. The sol-to-gel phase transition behaviors were affected by the concentrations of chitosan, DGP and the model drug levocetirizine dihydrochloride (LD). The developed hydrogel presented a characteristic of a rapid release at the initial period followed by a sustained release and remarkably enhanced the cornea penetration of LD. The results of ocular irritation demonstrated the excellent ocular tolerance of the hydrogel. The ocular residence time for the hydrogel was significantly prolonged compared with eye drops. The drug-loaded hydrogel produced more effective anti-allergic conjunctivitis effects compared with LD aqueous solution. These results showed that the chitosan/DGP thermosensitive hydrogel could be used as an ideal ocular drug delivery system in terms of the suitable sol-gel transition temperature, mild pH environment in the hydrogel as well as the organic solvent free.

Creating Drug Solubilization Compartments via Phase Separation in Multicomponent Buccal Patches Prepared by Direct Hot Melt Extrusion-Injection Molding.

PubMed

Alhijjaj, Muqdad; Bouman, Jacob; Wellner, Nikolaus; Belton, Peter; Qi, Sheng

2015-12-07

Creating in situ phase separation in solid dispersion based formulations to allow enhanced functionality of the dosage form, such as improving dissolution of poorly soluble model drug as well as being mucoadhesive, can significantly maximize the in vitro and in vivo performance of the dosage form. This formulation strategy can benefit a wide range of solid dosage forms for oral and alternative routes of delivery. This study using buccal patches as an example created separated phases in situ of the buccal patches by selecting the excipients with different miscibility with each other and the model drug. The quaternary dispersion based buccal patches containing PEG, PEO, Tween 80, and felodipine were prepared by direct hot melt extrusion-injection molding (HME-IM). The partial miscibility between Tween 80 and semicrystalline PEG-PEO led to the phase separation after extrusion. The Tween phases acted as drug solubilization compartments, and the PEG-PEO phase had the primary function of providing mucoadhesion and carrier controlled dissolution. As felodipine was preferably solubilized in the amorphous regions of PEG-PEO, the high crystallinity of PEG-PEO resulted in an overall low drug solubilizing capacity. Tween 80 was added to improve the solubilization capacity of the system as the model drug showed good solubility in Tween. Increasing the drug loading led to the supersaturation of drug in Tween compartments and crystalline drug dispersed in PEG-PEO phases. The spatial distribution of these phase-separated compartments was mapped using X-ray micro-CT, which revealed that the domain size and heterogeneity of the phase separation increased with increasing the drug loading. The outcome of this study provides new insights into the applicability of in situ formed phase separation as a formulation strategy for the delivery of poorly soluble drugs and demonstrated the basic principle of excipient selection for such technology.

Concentration-dependent rheological properties of ECM hydrogel for intracerebral delivery to a stroke cavity

PubMed Central

Massensini, Andre R.; Ghuman, Harmanvir; Saldin, Lindsey T.; Medberry, Christopher J.; Keane, Timothy J.; Nicholls, Francesca J.; Velankar, Sachin S.; Badylak, Stephen F.; Modo, Michel

2015-01-01

Biomaterials composed of mammalian extracellular matrix (ECM) promote constructive tissue remodeling with minimal scar tissue formation in many anatomical sites. However, the optimal shape and form of ECM scaffold for each clinical application can vary markedly. ECM hydrogels have been shown to promote chemotaxis and differentiation of neuronal stem cells, but minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form. These ECM materials can be manufactured to exist in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. Implantation into the lesion cavity after a stroke could hence provide a means to support endogenous repair mechanisms. Herein, we characterize the rheological properties of an ECM hydrogel composed of urinary bladder matrix (UBM) that influence its delivery and in vivo interaction with host tissue. There was a notable concentration-dependence in viscosity, stiffness, and elasticity; all characteristics important for minimally invasive intracerebral delivery. An efficient MRI-guided injection with drainage of fluid from the cavity is described to assess in situ hydrogel formation and ECM retention at different concentrations (0, 1, 2, 3, 4, and 8 mg/mL). Only ECM concentrations >3 mg/mL gelled within the stroke cavity. Lower concentrations were not retained within the cavity, but extensive permeation of the liquid phase ECM into the peri-infarct area was evident. The concentration of ECM hydrogel is hence an important factor affecting gelation, host-biomaterial interface, as well intra-lesion distribution. PMID:26318805

Microemulsion-loaded hydrogel formulation of butenafine hydrochloride for improved topical delivery.

PubMed

Pillai, Anilkumar B; Nair, Jyothilaksmi V; Gupta, Nishant Kumar; Gupta, Swati

2015-09-01

Topical microemulsion systems for the antifungal drug, butenafine hydrochloride (BTF) were designed and developed to overcome the problems associated with the cutaneous delivery due to poor water solubility. The solubility of BTF in oils, surfactants and co-surfactants was evaluated to screen the components of the microemulsion. Isopropyl palmitate was used as the oil phase, aerosol OT as the surfactant and sorbitan monooleate as co-surfactant. The pseudoternary diagrams were constructed to identify the area of microemulsion existence and optimum systems were designed. The systems were assessed for drug-loading efficiency and characterized for pH, robustness to dilution, globule size, drug content and stability. Viscosity analysis, spreadability, drug content assay, ex vivo skin permeation study and antifungal activity assay were performed for the optimized microemulsion-loaded hydrogel. The optimized BTF microemulsion had a small and uniform globule size. The incorporation of microemulsion system into Carbopol 940 gel was found to be better as compared to sodium alginate or hydroxyl propyl methyl cellulose (HPMC K4 M) gel. The developed gel has shown better ex vivo skin permeation and antifungal activity when compared to marketed BTF cream. Thus, the results provide a basis for the successful delivery of BTF from microemulsion-loaded hydrogel formulation, which resulted in improved penetration of drug and antifungal activity in comparison with commercial formulation of BTF.

Formulation Development and Toxicity Assessment of Triacetin Mediated Nanoemulsions as Novel Delivery Systems for Rapamycin

PubMed Central

Sobhani, Hamideh; Tarighi, Parastoo; Ostad, Seyed Nasser; Shafaati, Alireza; Nafissi-Varcheh, Nastaran; Aboofazeli, Reza

2015-01-01

The aim of this investigation was to design and develop nanoemulsions (NEs) as novel delivery systems for rapamycin. Phase behavior of quaternary systems composed of Traicetin (as oil), various surfactants and co-surfactants and water at different surfactant/co-surfactant weight ratios was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region of the phase diagrams, depending upon the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 1 mg/mL of the drug. The NEs were characterized and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release from the selected formulations was determined for a period of 48 h using a dialysis sac. The assay of rapamycin was carried out using an HPLC technique. The effect of NEs on the viability of SKBR-3 cells was evaluated by MTT assay. The integrity of Caco-2 cell monolayers was measured by Transepithelial Electrical Resistance (TEER) and the transport of rapamycin-loaded NEs across Caco-2 cell monolayers was then assessed. The uptake of NEs by SKBR-3 cells was also investigated using florescence microscopy. Maximum drug release was observed in case of 4 formulations prepared with Tween 80 and Tween 20. MTT test results revealed different toxicity of NEs for SKBR-3 cell line and TEER demonstrated that formulations containing Tween 20 caused a more considerable decrease in cell integrity in comparison with those prepared with Tween 80. The results obtained from cellular uptake experiments were in consistent with those obtained from TEER and cytotoxicity experiments. PMID:26185501

Formulation Development and Toxicity Assessment of Triacetin Mediated Nanoemulsions as Novel Delivery Systems for Rapamycin.

PubMed

Sobhani, Hamideh; Tarighi, Parastoo; Ostad, Seyed Nasser; Shafaati, Alireza; Nafissi-Varcheh, Nastaran; Aboofazeli, Reza

2015-01-01

The aim of this investigation was to design and develop nanoemulsions (NEs) as novel delivery systems for rapamycin. Phase behavior of quaternary systems composed of Traicetin (as oil), various surfactants and co-surfactants and water at different surfactant/co-surfactant weight ratios was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region of the phase diagrams, depending upon the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 1 mg/mL of the drug. The NEs were characterized and subjected to stability tests at various temperatures over 9-12 months. Cumulative drug release from the selected formulations was determined for a period of 48 h using a dialysis sac. The assay of rapamycin was carried out using an HPLC technique. The effect of NEs on the viability of SKBR-3 cells was evaluated by MTT assay. The integrity of Caco-2 cell monolayers was measured by Transepithelial Electrical Resistance (TEER) and the transport of rapamycin-loaded NEs across Caco-2 cell monolayers was then assessed. The uptake of NEs by SKBR-3 cells was also investigated using florescence microscopy. Maximum drug release was observed in case of 4 formulations prepared with Tween 80 and Tween 20. MTT test results revealed different toxicity of NEs for SKBR-3 cell line and TEER demonstrated that formulations containing Tween 20 caused a more considerable decrease in cell integrity in comparison with those prepared with Tween 80. The results obtained from cellular uptake experiments were in consistent with those obtained from TEER and cytotoxicity experiments.

pH-driven colloidal transformations based on the vasoactive drug nicergoline.

PubMed

Salentinig, Stefan; Tangso, Kristian J; Hawley, Adrian; Boyd, Ben J

2014-12-16

The structure of colloidal self-assembled drug delivery systems can be influenced by intermolecular interactions between drug and amphiphilic molecules, and is important to understand in the context of designing improved delivery systems. Controlling these structures can enable controlled or targeted release systems for poorly water-soluble drugs. Here we present the interaction of the hydrophobic vasoactive drug nicergoline with the internal structure of nanostructured emulsion particles based on the monoglyceride-water system. Addition of this drug leads to modification of the internal bicontinuous cubic structure to generate highly pH-responsive systems. The colloidal structures were characterized with small-angle X-ray scattering and visualized using cryogenic transmission electron microscopy. Reversible transformations to inverse micelles at high pH, vesicles at low pH, and the modification of the spacing of the bicontinuous cubic structure at intermediate pH were observed, and enabled the in situ determination of an apparent pKa for the drug in this system--a difficult task using solution-based approaches. The characterization of this phase behavior is also highly interesting for the design of pH-responsive controlled release systems for poorly water-soluble drug molecules.

Anticoagulant effects of inhaled unfractionated heparin in the dog as determined by partial thromboplastin time and factor Xa activity.

PubMed

Manion, Jill S; Thomason, John M; Langston, Vernon C; Claude, Andrew K; Brooks, Marjory B; Mackin, Andrew J; Lunsford, Kari V

2016-01-01

To evaluate the anticoagulant effects of inhaled heparin in dogs. This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage fluid (BALf) was collected to generate an in vitro calibration curve to relate heparin concentration to the activated partial thromboplastin time (aPTT). In phase 2, heparin was administered via nebulization to determine the threshold dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant activity of inhaled heparin was determined by measurement of BALf anti-Xa activity and aPTT. University teaching hospital. Six healthy intact female Walker Hounds were used in this study. Two dogs were used for each phase. Inhaled unfractionated sodium heparin was administered in doses ranging from 50,000 to 200,000 IU. In vitro addition of heparin to BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000 IU failed to prolong systemic aPTT, and a threshold dose could not be determined. No significant local anticoagulant effects were detected. Even at doses higher than those known to be effective in people, inhaled heparin appears to have no detectable local or systemic anticoagulant effects in dogs with the current delivery method. © Veterinary Emergency and Critical Care Society 2015.

Defining failed induction of labor.

PubMed

Grobman, William A; Bailit, Jennifer; Lai, Yinglei; Reddy, Uma M; Wapner, Ronald J; Varner, Michael W; Thorp, John M; Leveno, Kenneth J; Caritis, Steve N; Prasad, Mona; Tita, Alan T N; Saade, George; Sorokin, Yoram; Rouse, Dwight J; Blackwell, Sean C; Tolosa, Jorge E

2018-01-01

While there are well-accepted standards for the diagnosis of arrested active-phase labor, the definition of a "failed" induction of labor remains less certain. One approach to diagnosing a failed induction is based on the duration of the latent phase. However, a standard for the minimum duration that the latent phase of a labor induction should continue, absent acute maternal or fetal indications for cesarean delivery, remains lacking. The objective of this study was to determine the frequency of adverse maternal and perinatal outcomes as a function of the duration of the latent phase among nulliparous women undergoing labor induction. This study is based on data from an obstetric cohort of women delivering at 25 US hospitals from 2008 through 2011. Nulliparous women who had a term singleton gestation in the cephalic presentation were eligible for this analysis if they underwent a labor induction. Consistent with prior studies, the latent phase was determined to begin once cervical ripening had ended, oxytocin was initiated, and rupture of membranes had occurred, and was determined to end once 5-cm dilation was achieved. The frequencies of cesarean delivery, as well as of adverse maternal (eg, postpartum hemorrhage, chorioamnionitis) and perinatal (eg, a composite frequency of seizures, sepsis, bone or nerve injury, encephalopathy, or death) outcomes, were compared as a function of the duration of the latent phase (analyzed with time both as a continuous measure and categorized in 3-hour increments). A total of 10,677 women were available for analysis. In the vast majority (96.4%) of women, the active phase had been reached by 15 hours. The longer the duration of a woman's latent phase, the greater her chance of ultimately undergoing a cesarean delivery (P < .001, for time both as a continuous and categorical independent variable), although >40% of women whose latent phase lasted ≥18 hours still had a vaginal delivery. Several maternal morbidities, such as postpartum hemorrhage (P < .001) and chorioamnionitis (P < .001), increased in frequency as the length of latent phase increased. Conversely, the frequencies of most adverse perinatal outcomes were statistically stable over time. The large majority of women undergoing labor induction will have entered the active phase by 15 hours after oxytocin has started and rupture of membranes has occurred. Maternal adverse outcomes become statistically more frequent with greater time in the latent phase, although the absolute increase in frequency is relatively small. These data suggest that cesarean delivery should not be undertaken during the latent phase prior to at least 15 hours after oxytocin and rupture of membranes have occurred. The decision to continue labor beyond this point should be individualized, and may take into account factors such as other evidence of labor progress. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting solubilisation features of ternary phase diagrams of fully dilutable lecithin linker microemulsions.

PubMed

Nouraei, Mehdi; Acosta, Edgar J

2017-06-01

Fully dilutable microemulsions (μEs), used to design self-microemulsifying delivery system (SMEDS), are formulated as concentrate solutions containing oil and surfactants, without water. As water is added to dilute these systems, various μEs are produced (water-swollen reverse micelles, bicontinuous systems, and oil-swollen micelles), without the onset of phase separation. Currently, the formulation dilutable μEs follows a trial and error approach that has had a limited success. The objective of this work is to introduce the use of the hydrophilic-lipophilic-difference (HLD) and net-average-curvature (NAC) frameworks to predict the solubilisation features of ternary phase diagrams of lecithin-linker μEs and the use of these predictions to guide the formulation of dilutable μEs. To this end, the characteristic curvatures (Cc) of soybean lecithin (surfactant), glycerol monooleate (lipophilic linker) and polyglycerol caprylate (hydrophilic linker) and the equivalent alkane carbon number (EACN) of ethyl caprate (oil) were obtained via phase scans with reference surfactant-oil systems. These parameters were then used to calculate the HLD of lecithin-linkers-ethyl caprate microemulsions. The calculated HLDs were able to predict the phase transitions observed in the phase scans. The NAC was then used to fit and predict phase volumes obtained from salinity phase scans, and to predict the solubilisation features of ternary phase diagrams of the lecithin-linker formulations. The HLD-NAC predictions were reasonably accurate, and indicated that the largest region for dilutable μEs was obtained with slightly negative HLD values. The NAC framework also predicted, and explained, the changes in microemulsion properties along dilution lines. Copyright © 2017 Elsevier Inc. All rights reserved.

IDC Integrated Master Plan.

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

Clifford, David J.; Harris, James M.

2014-12-01

This is the IDC Re-Engineering Phase 2 project Integrated Master Plan (IMP). The IMP presents the major accomplishments planned over time to re-engineer the IDC system. The IMP and the associate Integrated Master Schedule (IMS) are used for planning, scheduling, executing, and tracking the project technical work efforts. REVISIONS Version Date Author/Team Revision Description Authorized by V1.0 12/2014 IDC Re- engineering Project Team Initial delivery M. Harris

MO-FG-BRA-08: Swarm Intelligence-Based Personalized Respiratory Gating in Lung SAbR

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

Modiri, A; Sabouri, P; Sawant, A

Purpose: Respiratory gating is widely deployed as a clinical motion-management strategy in lung radiotherapy. In conventional gating, the beam is turned on during a pre-determined phase window; typically, around end-exhalation. In this work, we challenge the notion that end-exhalation is always the optimal gating phase. Specifically, we use a swarm-intelligence-based, inverse planning approach to determine the optimal respiratory phase and MU for each beam with respect to (i) the state of the anatomy at each phase and (ii) the time spent in that state, estimated from long-term monitoring of the patient’s breathing motion. Methods: In a retrospective study of fivemore » lung cancer patients, we compared the dosimetric performance of our proposed personalized gating (PG) with that of conventional end-of-exhale gating (CEG) and a previously-developed, fully 4D-optimized plan (combined with MLC tracking delivery). For each patient, respiratory phase probabilities (indicative of the time duration of the phase) were estimated over 2 minutes from lung tumor motion traces recorded previously using the Synchrony system (Accuray Inc.). Based on this information, inverse planning optimization was performed to calculate the optimal respiratory gating phase and MU for each beam. To ensure practical deliverability, each PG beam was constrained to deliver the assigned MU over a time duration comparable to that of CEG delivery. Results: Maximum OAR sparing for the five patients achieved by the PG and the 4D plans compared to CEG plans was: Esophagus Dmax [PG:57%, 4D:37%], Heart Dmax [PG:71%, 4D:87%], Spinal cord Dmax [PG:18%, 4D:68%] and Lung V13 [PG:16%, 4D:31%]. While patients spent the most time in exhalation, the PG-optimization chose end-exhale only for 28% of beams. Conclusion: Our novel gating strategy achieved significant dosimetric improvements over conventional gating, and approached the upper limit represented by fully 4D optimized planning while being significantly simpler and more clinically translatable. This work was partially supported through research funding from National Institutes of Health (R01CA169102) and Varian Medical Systems, Palo Alto, CA, USA.« less

Self-microemulsifying drug delivery system improves curcumin dissolution and bioavailability.

PubMed

Wu, Xuemei; Xu, Jianhua; Huang, Xiuwang; Wen, Caixia

2011-01-01

Curcumin has a wide spectrum of biological and pharmacological activities, but it has not yet been approved as a therapeutic agent because of its low solubility and stability in aqueous solution, and the relatively low bioavailability in vivo. To overcome these limitations, self-microemulsifying drug delivery system (SMEDDS) of curcumin was developed. Various oils, surfactants, and cosurfactants were selected to optimize the formulation. Pseudoternary phase diagrams were constructed and orthogonal design was used to compare the oil-in-water (o/w) microemulsion-forming capacity of different oils/surfactants/cosurfactants. The solubility of curcumin in various oils and cosurfactants was determined to find suitable ingredients with a good solubilizing capacity. Droplet size was measured to obtain the concentration of oil, surfactant, and cosurfactant for forming stable microemulsion. Furthermore, its quality and bioavailability in mice were assessed. Pseudoternary phase diagrams and solubility test showed that the formulation of SMEDDS composed of 20% ethanol, 60% Cremophor RH40®, and 20% isopropyl myristate, in which the concentration of curcumin reached 50 mg/mL. Curcumin was released completely from SMEDDS at 10 minutes. The developed SMEDDS formulation improved the oral bioavailability of curcumin significantly, and the relative oral bioavailability of SMEDDS compared with curcumin suspension was 1213%. The SMEDDS can significantly increase curcumin dissolution in vitro and bioavailability in vivo.

Enhanced oral bioavailability of lurasidone by self-nanoemulsifying drug delivery system in fasted state.

PubMed

Miao, Yanfei; Sun, Jiqin; Chen, Guoguang; Lili, Ren; Ouyang, Pingkai

2016-08-01

The purpose of this work was to develop a new formulation to enhance the bioavailability and reduce the food effect of lurasidone using self-nanoemulsifying drug delivery systems (SNEDDSs). The formulation of lurasidone-SNEDDS was selected by the solubility and pseudo-ternary phase diagram studies. The prepared lurasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis, zeta potential and in vitro drug release. Lurasidone-SNEDDSs were administered to beagle dogs in fed and fasted state and their pharmacokinetics were compared to commercial available tablet as a control. The result showed lurasidone-SNEDDS was successfully prepared using Capmul MCM, Tween 80 and glycerol as oil phase, surfactant and co-surfactant, respectively. In vitro drug release studies indicated that the lurasidone-SNEDDS showed improved drug release profiles and the release behavior was not affected by the medium pH with total drug release of over 90% within 5 min. Pharmacokinetic study showed that the AUC(0-∞) and Cmax for lurasidone-SNEDDS are similar in the fasted and fed state, indicating essentially there is no food effect on the drug absorption. It was concluded that enhanced bioavailability and no food effect of lurasidone had been achieved by using SNEDDS.

Localized In Situ Nanoemulgel Drug Delivery System of Quercetin for Periodontitis: Development and Computational Simulations.

PubMed

Aithal, Gururaj C; Nayak, Usha Yogendra; Mehta, Chetan; Narayan, Reema; Gopalkrishna, Pratibha; Pandiyan, Sudharsan; Garg, Sanjay

2018-06-06

This study was aimed at formulating a bioabsorbable, controlled-release, nanoemulgel of Quercetin, a potent antimicrobial and anti-inflammatory agent for the treatment of periodontitis that could improve its solubility and bioavailability. Screening of components was carried out based on the solubility studies. Nanoemulsion containing cinnamon oil as the oil phase, tween 80 and Carbitol ® as the surfactant-cosurfactant mixture (S mix ) and water as the aqueous phase containing 125 µg/200 µL of Quercetin was prepared by using spontaneous emulsification method. Nanoemulgel was prepared using 23% w / v poloxamer 407 as gel base. Comprehensive evaluation of the formulated nanoemulgel was carried out, and the optimized formulation was studied for drug release using Franz vertical diffusion cells. The formulated nanoemulgelexhibited a remarkable release of 92.4% of Quercetin at the end of 6 h, as compared to that of pure Quercetin-loaded gel (<3% release). The viscosity of the prepared nanoemulgel was found to be 30,647 ± 0.32 cPs at 37 °C. Also, molecular dynamics (MD) simulation was utilized to understand the gelation process and role of each component in the formulation. The present study revealed that the developed nanoemulgel of Quercetin could be a potential delivery system for clinical testing in periodontitis.

Induction of labor in a contemporary obstetric cohort.

PubMed

Laughon, S Katherine; Zhang, Jun; Grewal, Jagteshwar; Sundaram, Rajeshwari; Beaver, Julie; Reddy, Uma M

2012-06-01

We sought to describe details of labor induction, including precursors and methods, and associated vaginal delivery rates. This was a retrospective cohort study of 208,695 electronic medical records from 19 hospitals across the United States, 2002 through 2008. Induction occurred in 42.9% of nulliparas and 31.8% of multiparas and elective or no recorded indication for induction at term occurred in 35.5% and 44.1%, respectively. Elective induction at term in multiparas was highly successful (vaginal delivery 97%) compared to nulliparas (76.2%). For all precursors, cesarean delivery was more common in nulliparas in the latent compared to active phase of labor. Regardless of method, vaginal delivery rates were higher with a ripe vs unripe cervix, particularly for multiparas (86.6-100%). Induction of labor was a common obstetric intervention. Selecting appropriate candidates and waiting longer for labor to progress into the active phase would make an impact on decreasing the national cesarean delivery rate. Published by Mosby, Inc.

Induction of Labor in a Contemporary Obstetric Cohort

PubMed Central

Laughon, S. Katherine; Zhang, Jun; Grewal, Jagteshwar; Sundaram, Rajeshwari; Beaver, Julie; Reddy, Uma M.

2012-01-01

Objective To describe details of labor induction, including precursors and methods, and associated vaginal delivery rates. Study Design A retrospective cohort study of 208,695 electronic medical records from 19 hospitals across the United States, 2002–2008. Results Induction occurred in 42.9% of nulliparas and 31.8% of multiparas and elective or no recorded indication for induction at term occurred in 35.5% and 44.1%, respectively. Elective induction at term in multiparas was highly successful (vaginal delivery 97%) compared to nulliparas (76.2%). For all precursors, cesarean delivery was more common in nulliparas in the latent compared to active phase of labor. Regardless of method, vaginal delivery rates were higher with a ripe versus unripe cervix, particularly for multiparas (86.6 – 100%). Conclusions Induction of labor was a common obstetric intervention. Selecting appropriate candidates and waiting longer for labor to progress into the active phase would make an impact on decreasing the national cesarean delivery rate. PMID:22520652

Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications.

PubMed

Gomes, Carmen; Moreira, Rosana G; Castell-Perez, Elena

2011-03-01

Eugenol and trans-cinnamaldehyde are natural compounds known to be highly effective antimicrobials; however, both are hydrophobic molecules, a limitation to their use within the food industry. The goal of this study was to synthesize spherical poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped eugenol and trans-cinnamaldehyde for future antimicrobial delivery applications. The emulsion evaporation method was used to form the nanoparticles in the presence of poly (vinyl alcohol) (PVA) as a surfactant. The inclusion of antimicrobial compounds into the PLGA nanoparticles was accomplished in the organic phase. Synthesis was followed by ultrafiltration (performed to eliminate the excess of PVA and antimicrobial compound) and freeze-drying. The nanoparticles were characterized by their shape, size, entrapment efficiency, and antimicrobial efficiency. The entrapment efficiency for eugenol and trans-cinnamaldehyde was approximately 98% and 92%, respectively. Controlled release experiments conducted in vitro at 37 °C and 100 rpm for 72 h showed an initial burst followed by a slower rate of release of the antimicrobial entrapped inside the PLGA matrix. All loaded nanoparticles formulations proved to be efficient in inhibiting growth of Salmonella spp. (Gram-negative bacterium) and Listeria spp. (Gram-positive bacterium) with concentrations ranging from 20 to 10 mg/mL. Results suggest that the application of these antimicrobial nanoparticles in food systems may be effective at inhibiting specific pathogens. Nanoencapsulation of lipophilic antimicrobial compounds has great potential for improving the effectiveness and efficiency of delivery in food systems. This study consisted of synthesizing PLGA nanoparticles with entrapped eugenol and trans-cinnamaldehyde. By characterizing these new delivery systems, one can understand the controlled-release mechanism and antimicrobial efficiency that provides a foundation that will enable food manufacturers to design smart food systems for future delivery applications, including packaging and processing, capable of ensuring food safety to consumers.

SHARP's systems engineering challenge: rectifying integrated product team requirements with performance issues in an evolutionary spiral development acquisition

NASA Astrophysics Data System (ADS)

Kuehl, C. Stephen

2003-08-01

Completing its final development and early deployment on the Navy's multi-role aircraft, the F/A-18 E/F Super Hornet, the SHAred Reconnaissance Pod (SHARP) provides the war fighter with the latest digital tactical reconnaissance (TAC Recce) Electro-Optical/Infrared (EO/IR) sensor system. The SHARP program is an evolutionary acquisition that used a spiral development process across a prototype development phase tightly coupled into overlapping Engineering and Manufacturing Development (EMD) and Low Rate Initial Production (LRIP) phases. Under a tight budget environment with a highly compressed schedule, SHARP challenged traditional acquisition strategies and systems engineering (SE) processes. Adopting tailored state-of-the-art systems engineering process models allowd the SHARP program to overcome the technical knowledge transition challenges imposed by a compressed program schedule. The program's original goal was the deployment of digital TAC Recce mission capabilities to the fleet customer by summer of 2003. Hardware and software integration technical challenges resulted from requirements definition and analysis activities performed across a government-industry led Integrated Product Team (IPT) involving Navy engineering and test sites, Boeing, and RTSC-EPS (with its subcontracted hardware and government furnished equipment vendors). Requirements development from a bottoms-up approach was adopted using an electronic requirements capture environment to clarify and establish the SHARP EMD product baseline specifications as relevant technical data became available. Applying Earned-Value Management (EVM) against an Integrated Master Schedule (IMS) resulted in efficiently managing SE task assignments and product deliveries in a dynamically evolving customer requirements environment. Application of Six Sigma improvement methodologies resulted in the uncovering of root causes of errors in wiring interconnectivity drawings, pod manufacturing processes, and avionics requirements specifications. Utilizing the draft NAVAIR SE guideline handbook and the ANSI/EIA-632 standard: Processes for Engineering a System, a systems engineering tailored process approach was adopted for the accelerated SHARP EMD prgram. Tailoring SE processes in this accelerated product delivery environment provided unique opportunities to be technically creative in the establishment of a product performance baseline. This paper provides an historical overview of the systems engineering activities spanning the prototype phase through the EMD SHARP program phase, the performance requirement capture activities and refinement process challenges, and what SE process improvements can be applied to future SHARP-like programs adopting a compressed, evolutionary spiral development acquisition paradigm.

Engineered Hydrogels for Local and Sustained Delivery of RNA-Interference Therapies.

PubMed

Wang, Leo L; Burdick, Jason A

2017-01-01

It has been nearly two decades since RNA-interference (RNAi) was first reported. While there are no approved clinical uses, several phase II and III clinical trials suggest the great promise of RNAi therapeutics. One challenge for RNAi therapies is the controlled localization and sustained presentation to target tissues, to both overcome systemic toxicity concerns and to enhance in vivo efficacy. One approach that is emerging to address these limitations is the entrapment of RNAi molecules within hydrogels for local and sustained release. In these systems, nucleic acids are either delivered as siRNA conjugates or within nanoparticles. A plethora of hydrogels has been implemented using these approaches, including both traditional hydrogels that have already been developed for other applications and new hydrogels developed specifically for RNAi delivery. These hydrogels have been applied to various applications in vivo, including cancer, bone regeneration, inflammation and cardiac repair. This review will examine the design and implementation of such hydrogel RNAi systems and will cover the most recent applications of these systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A region addresses patient safety.

PubMed

Feinstein, Karen Wolk; Grunden, Naida; Harrison, Edward I

2002-06-01

The Pittsburgh Regional Healthcare Initiative (PRHI) is a coalition of 35 hospitals, 4 major insurers, more than 30 major and small-business health care purchasers, dozens of corporate and civic leaders, organized labor, and partnerships with state and federal government all working together to deliver perfect patient care throughout Southwestern Pennsylvania. PRHI believes that in pursuing perfection, many of the challenges facing today's health care delivery system (eg, waste and error in the delivery of care, rising costs, frustration and shortage among clinicians and workers, financial distress, overcapacity, and lack of access to care) will be addressed. PRHI has identified patient safety (nosocomial infections and medication errors) and 5 clinical areas (obstetrics, orthopedic surgery, cardiac surgery, depression, and diabetes) as ideal starting points. In each of these areas of work, PRHI partners have assembled multifacility/multidisciplinary groups charged with defining perfection, establishing region-wide reporting systems, and devising and implementing recommended improvement strategies and interventions. Many design and conceptual elements of the PRHI strategy are adapted from the Toyota Production System and its Pittsburgh derivative, the Alcoa Business System. PRHI is in the proof-of-concept phase of development.

Sex and menstrual cycle effects on chronic oral cocaine self-administration in rhesus monkeys: Effects of a nondrug alternative reward

PubMed Central

Carroll, Marilyn E.; Collins, Molly; Kohl, Emily A.; Johnson, Seth; Dougen, Ben

2016-01-01

Background In previous studies female monkeys self-administered more oral phencyclidine (PCP) than males, and PCP intake differed by phase of menstrual cycle. Objectives The purpose of this study was to examine sex and hormonal influences on oral cocaine self-administration in male and female rhesus monkeys in the follicular vs. luteal phases of the menstrual cycle, with concurrent access to an alternative nondrug reward, saccharin (SACC) vs. water. Materials and methods Concurrent access to cocaine (0.2, 0.4 and 0.8 mg/ml) and SACC or water was available from two drinking spouts under concurrent fixed-ratio (FR) 2, 4, and 8 schedules during daily 3-h sessions. Results Cocaine deliveries were similar in males and females in the females’ luteal phase, but cocaine deliveries were higher in females during the follicular phase than the luteal phase and compared to males. When SACC was available cocaine deliveries were reduced in females in the follicular phase of the cycle, and cocaine intake (mg/kg) was reduced in males and in females’ follicular and luteal phases. Conclusions Access to concurrent SACC (vs. water) reduced cocaine intake (mg/kg) in males and in females during both menstrual phases, and the magnitude of the reduction in cocaine intake was greatest during the females’ follicular phase. Thus, a nondrug alternative reward, SACC, is a viable alternative treatment for reducing cocaine’s rewarding effects on male and female monkeys, and reductions in cocaine-seeking were optimal in the females’ luteal phase. PMID:27318989

Expert system verification and validation study. Phase 2: Requirements identification. Delivery 1: Updated survey report

NASA Technical Reports Server (NTRS)

1990-01-01

The purpose is to report the state-of-the-practice in Verification and Validation (V and V) of Expert Systems (ESs) on current NASA and Industry applications. This is the first task of a series which has the ultimate purpose of ensuring that adequate ES V and V tools and techniques are available for Space Station Knowledge Based Systems development. The strategy for determining the state-of-the-practice is to check how well each of the known ES V and V issues are being addressed and to what extent they have impacted the development of Expert Systems.

Assessment of Power Quality based on Fuzzy Logic and Discrete Wavelet Transform for Nonstationary Disturbances

NASA Astrophysics Data System (ADS)

Sinha, Pampa; Nath, Sudipta

2010-10-01

The main aspects of power system delivery are reliability and quality. If all the customers of a power system get uninterrupted power through the year then the system is considered to be reliable. The term power quality may be referred to as maintaining near sinusoidal voltage at rated frequency at the consumers end. The power component definitions are defined according to the IEEE Standard 1459-2000 both for single phase and three phase unbalanced systems based on Fourier Transform (FFT). In the presence of nonstationary power quality (PQ) disturbances results in accurate values due to its sensitivity to the spectral leakage problem. To overcome these limitations the power quality components are calculated using Discrete Wavelet Transform (DWT). In order to handle the uncertainties associated with electric power systems operations fuzzy logic has been incorporated in this paper. A new power quality index has been introduced here which can assess the power quality under nonstationary disturbances.

In-situ phase transition from microemulsion to liquid crystal with the potential of prolonged parenteral drug delivery.

PubMed

Ren, Xiazhong; Svirskis, Darren; Alany, Raid G; Zargar-Shoshtari, Sara; Wu, Zimei

2012-07-15

This study is the first to investigate and demonstrate the potential of microemulsions (MEs) for sustained release parenteral drug delivery, due to phase transition behavior in aqueous environments. Phase diagrams were constructed with Miglyol 812N oil and a blend of (co)surfactants Solutol HS 15 and Span 80 with ethanol. Liquid crystal (LC) and coarse emulsion (CE) regions were found adjacent to the ME region in the water-rich corner of the phase diagram. Two formulations were selected, a LC-forming ME and a CE-forming ME and each were investigated with respect to their rheology, particle size, drug release profiles and particularly, the phase transition behavior. The spreadability in an aqueous environment was determined and release profiles from MEs were generated with gamma-scintigraphy. The CE-forming ME dispersed readily in an aqueous environment, whereas the LC-forming ME remained in a contracted region possibly due to the transition of ME to LC at the water/ME interface. Gamma-scintigraphy showed that the LC-forming ME had minimal spreadability and a slow release of (99m)Tc in the first-order manner, suggesting phase conversion at the interface. In conclusion, owing to the potential of phase transition, LC-forming MEs could be used as extravascular injectable drug delivery vehicles for prolonged drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

Nanoemulsions as self-emulsified drug delivery carriers for enhanced permeability of the poorly water-soluble selective β₁-adrenoreceptor blocker Talinolol.

PubMed

Ghai, Damanjeet; Sinha, Vivek Ranjan

2012-07-01

To enhance the bioavailability of the poorly water-soluble drug talinolol, a self-nanoemulsifying drug delivery system (SNEDDS) comprising 5% (w/v) Brij-721 ethanolic solution (Smix), triacetin, and water, in the ratio of 40:20:40 (% w/w) was developed by constructing pseudo-ternary phase diagrams and evaluated for droplet size, polydispersity index, and surface morphology of nanoemulsions. The effect of nanodrug carriers on drug release and permeability was assessed using stripped porcine jejunum and everted rat gut sac method and compared with hydroalcoholic drug solution, oily solution, and conventional emulsion and suspension. The SNEDDS showed a significant (P < 0.001) increase in drug release, permeability, and in vivo bioavailability as compared to drug suspension. This may be attributed to increased solubility and enhanced permeability of the drug from nanosized emulsion. In this study, a self-nanoemulsifying drug delivery system was utilized to enhance the bioavailability of the poorly water-soluble beta-blocker talinolol. Significant increase in drug release, permeability, and in vivo bioavailability were demonstrated as compared to standard drug suspension. Copyright © 2012 Elsevier Inc. All rights reserved.

Porous PLGA microspheres tailored for dual delivery of biomolecules via layer-by-layer assembly.

PubMed

Go, Dewi P; Palmer, Jason A; Mitchell, Geraldine M; Gras, Sally L; O'Connor, Andrea J

2015-05-01

Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules. © 2014 Wiley Periodicals, Inc.

Transdermal delivery of paeonol using cubic gel and microemulsion gel

PubMed Central

Luo, Maofu; Shen, Qi; Chen, Jinjin

2011-01-01

Background The aim of this study was to develop new systems for transdermal delivery of paeonol, in particular microemulsion gel and cubic gel formulations. Methods Various microemulsion vehicles were prepared using isopropyl myristate as an oil phase, polyoxyethylated castor oil (Cremophor® EL) as a surfactant, and polyethylene glycol 400 as a cosurfactant. In the optimum microemulsion gel formulation, carbomer 940 was selected as the gel matrix, and consisted of 1% paeonol, 4% isopropyl myristate, 28% Cremophor EL/polyethylene glycol 400 (1:1), and 67% water. The cubic gel was prepared containing 3% paeonol, 30% water, and 67% glyceryl monooleate. Results A skin permeability test using excised rat skins indicated that both the cubic gel and microemulsion gel formulations had higher permeability than did the paeonol solution. An in vivo pharmacokinetic study done in rats showed that the relative bioavailability of the cubic gel and microemulsion gel was enhanced by about 1.51-fold and 1.28-fold, respectively, compared with orally administered paeonol suspension. Conclusion Both the cubic gel and microemulsion gel formulations are promising delivery systems to enhance the skin permeability of paeonol, in particular the cubic gel. PMID:21904450

ENHANCED PRACTICAL PHOTOSYNTHETIC CO2 MITIGATION

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

Dr. Gregory Kremer; Dr. David J. Bayless; Dr. Morgan Vis

2001-10-15

This report documents significant achievements in the Enhanced Practical Photosynthetic CO{sub 2} Mitigation project during the period from 10/03/2000 through 10/02/2001. Most of the achievements are milestones in our efforts to complete the tasks and subtasks that constitute the project objectives. This is the fourth quarterly report for this project, so it also serves as a year-1 project review. We have made significant progress on our Phase I objectives, and our current efforts are focused on fulfilling these research objectives ''on time'' relative to the project timeline. Overall, we believe that we are on schedule to complete Phase I activitiesmore » by 10/2002, which is the milestone date from the original project timeline. Our results to date concerning the individual factors which have the most significant effect on CO{sub 2} uptake are inconclusive, but we have gathered useful information about the effects of lighting, temperature and CO{sub 2} concentration on one particular organism (Nostoc) and significant progress has been made in identifying other organisms that are more suitable for use in the bioreactor due to their better tolerance for the high temperatures likely to be encountered in the flue gas stream. Our current tests are focused on one such thermophilic organism (Cyanidium), and an enlarged bioreactor system (CRF-2) has been prepared for testing this organism. Tests on the enhanced mass transfer CO{sub 2} absorption technique are underway and useful information is currently being collected concerning pressure drop. The solar collectors for the deep-penetration hybrid solar lighting system have been designed and a single solar collector tracking unit is being prepared for installation in the pilot scale bioreactor system currently under construction. Much progress has been made in designing the fiber optic light delivery system, but final selection of the ''optimum'' delivery system design depends on many factors, most significantly the configuration and orientation of the growth surfaces in the bioreactor. For the growth surface subsystem we have identified advantages and disadvantages for several candidate growth surface materials, we have built and tested various ''screen'' systems and fluid delivery systems, and we continue to test compatibility of the candidate materials with the organisms and with the moisture delivery and harvesting system designs. These tests will be ongoing until an ''optimum'' combination of growth surface material/organism type/harvesting system is identified. For the harvesting system, a nozzle-based water jet system has been shown to be effective, but it has disadvantages for the overall system design in terms of space utilization. A streamlined and integrated screen wetting/harvesting system design is currently under development and will be the focus of harvesting system tests in the foreseeable future. This report addresses each of the key project tasks as defined in the statement of work, giving both a summary of key accomplishments over the past year and a plan for future work.« less

Three-Dimensional Microphase Separation and Synergistic Permeability in Stacked Lipid–Polymer Hybrid Membranes

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

Kang, Minjee; Lee, Byeongdu; Leal, Cecilia

Here, we present new structures of soft-material thin films that augment the functionality of substrate-mediated delivery systems. A hybrid material composed of phospholipids and block copolymers adopts a multilayered membrane structure supported on a solid surface. The hybrid films comprise intentional intramembrane heterogeneities that register across multilayers. These stacked domains convey unprecedented enhancement and control of permeability of solutes across micrometer-thick films. Using grazing incidence X-ray scattering, phase contrast atomic force microscopy, and confocal microscopy, we observed that in each lamella, lipid and polymers partition unevenly within the membrane plane segregating into lipid- or polymer-rich domains. Interestingly, we found evidencemore » that like-domains align in registry across multilayers, thereby making phase separation three-dimensional. Phase boundaries exist over extended length scales to compensate the height mismatch between lipid and polymer molecules. We show that microphase separation in hybrid films can be exploited to augment the capability of drug-eluting substrates. Lipid–polymer hybrid films loaded with paclitaxel show synergistic permeability of drug compared to single-component counterparts. We present a thorough structural study of stacked lipid–polymer hybrid membranes and propose that the presence of registered domains and domain boundaries impart enhanced drug release functionality. This work offers new perspectives in designing thin films for controlled delivery applications« less

Three-Dimensional Microphase Separation and Synergistic Permeability in Stacked Lipid–Polymer Hybrid Membranes

DOE PAGES

Kang, Minjee; Lee, Byeongdu; Leal, Cecilia

2017-10-20

Here, we present new structures of soft-material thin films that augment the functionality of substrate-mediated delivery systems. A hybrid material composed of phospholipids and block copolymers adopts a multilayered membrane structure supported on a solid surface. The hybrid films comprise intentional intramembrane heterogeneities that register across multilayers. These stacked domains convey unprecedented enhancement and control of permeability of solutes across micrometer-thick films. Using grazing incidence X-ray scattering, phase contrast atomic force microscopy, and confocal microscopy, we observed that in each lamella, lipid and polymers partition unevenly within the membrane plane segregating into lipid- or polymer-rich domains. Interestingly, we found evidencemore » that like-domains align in registry across multilayers, thereby making phase separation three-dimensional. Phase boundaries exist over extended length scales to compensate the height mismatch between lipid and polymer molecules. We show that microphase separation in hybrid films can be exploited to augment the capability of drug-eluting substrates. Lipid–polymer hybrid films loaded with paclitaxel show synergistic permeability of drug compared to single-component counterparts. We present a thorough structural study of stacked lipid–polymer hybrid membranes and propose that the presence of registered domains and domain boundaries impart enhanced drug release functionality. This work offers new perspectives in designing thin films for controlled delivery applications« less

A single microfluidic chip with dual surface properties for protein drug delivery.

PubMed

Bokharaei, Mehrdad; Saatchi, Katayoun; Häfeli, Urs O

2017-04-15

Principles of double emulsion generation were incorporated in a glass microfluidic chip fabricated with two different surface properties in order to produce protein loaded polymer microspheres. The microspheres were produced by integrating two microfluidic flow focusing systems and a multi-step droplet splitting and mixing system into one chip. The chip consists of a hydrophobic and a hydrophilic section with two different heights, 12μm and 45μm, respectively. As a result, the protein is homogenously distributed throughout the polymer microsphere matrix, not just in its center (which has been studied before). In our work, the inner phase was bovine serum albumin (BSA) in phosphate buffered saline, the disperse phase was poly (lactic acid) in chloroform and the continuous phase was an aqueous solution of poly(vinyl alcohol). After solvent removal, BSA loaded microspheres with an encapsulation efficiency of up to 96% were obtained. Our results show the feasibility of producing microspheres loaded with a hydrophilic drug in a microfluidic system that integrates different microfluidic units into one chip. Copyright © 2017 Elsevier B.V. All rights reserved.

Temperature and pressure tuneable swollen bicontinuous cubic phases approaching nature's length scales.

PubMed

Barriga, H M G; Tyler, A I I; McCarthy, N L C; Parsons, E S; Ces, O; Law, R V; Seddon, J M; Brooks, N J

2015-01-21

Bicontinuous cubic structures offer enormous potential in applications ranging from protein crystallisation to drug delivery systems and have been observed in cellular membrane structures. One of the current bottlenecks in understanding and exploiting these structures is that cubic scaffolds produced in vitro are considerably smaller in size than those observed in biological systems, differing by almost an order of magnitude in some cases. We have addressed this technological bottleneck and developed a methodology capable of manufacturing highly swollen bicontinuous cubic membranes with length scales approaching those seen in vivo. Crucially, these cubic systems do not require the presence of proteins. We have generated highly swollen Im3m symmetry bicontinuous cubic phases with lattice parameters of up to 480 Å, composed of ternary mixtures of monoolein, cholesterol and negatively charged lipid (DOPS or DOPG) and we have been able to tune their lattice parameters. The swollen cubic phases are highly sensitive to both temperature and pressure; these structural changes are likely to be controlled by a fine balance between lipid headgroup repulsions and lateral pressure in the hydrocarbon chain region.

In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide.

PubMed

Sheshala, Ravi; Hong, Gan Chew; Yee, Wong Pui; Meka, Venkata Srikanth; Thakur, Raghu Raj Singh

2018-02-26

The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.

Nanocomposite capsules with directional, pulsed nanoparticle release.

PubMed

Udoh, Christiana E; Cabral, João T; Garbin, Valeria

2017-12-01

The precise spatiotemporal delivery of nanoparticles from polymeric capsules is required for applications ranging from medicine to materials science. These capsules derive key performance aspects from their overall shape and dimensions, porosity, and internal microstructure. To this effect, microfluidics provide an exceptional platform for emulsification and subsequent capsule formation. However, facile and robust approaches for nanocomposite capsule fabrication, exhibiting triggered nanoparticle release, remain elusive because of the complex coupling of polymer-nanoparticle phase behavior, diffusion, phase inversion, and directional solidification. We investigate a model system of polyelectrolyte sodium poly(styrene sulfonate) and 22-nm colloidal silica and demonstrate a robust capsule morphology diagram, achieving a range of internal morphologies, including nucleated and bicontinuous microstructures, as well as isotropic and non-isotropic external shapes. Upon dissolution in water, we find that capsules formed with either neat polymers or neat nanoparticles dissolve rapidly and isotropically, whereas bicontinuous, hierarchical, composite capsules dissolve via directional pulses of nanoparticle clusters without disrupting the scaffold, with time scales tunable from seconds to hours. The versatility, facile assembly, and response of these nanocomposite capsules thus show great promise in precision delivery.

Programmable Hydrogel Ionic Circuits for Biologically Matched Electronic Interfaces.

PubMed

Zhao, Siwei; Tseng, Peter; Grasman, Jonathan; Wang, Yu; Li, Wenyi; Napier, Bradley; Yavuz, Burcin; Chen, Ying; Howell, Laurel; Rincon, Javier; Omenetto, Fiorenzo G; Kaplan, David L

2018-06-01

The increased need for wearable and implantable medical devices has driven the demand for electronics that interface with living systems. Current bioelectronic systems have not fully resolved mismatches between engineered circuits and biological systems, including the resulting pain and damage to biological tissues. Here, salt/poly(ethylene glycol) (PEG) aqueous two-phase systems are utilized to generate programmable hydrogel ionic circuits. High-conductivity salt-solution patterns are stably encapsulated within PEG hydrogel matrices using salt/PEG phase separation, which route ionic current with high resolution and enable localized delivery of electrical stimulation. This strategy allows designer electronics that match biological systems, including transparency, stretchability, complete aqueous-based connective interface, distribution of ionic electrical signals between engineered and biological systems, and avoidance of tissue damage from electrical stimulation. The potential of such systems is demonstrated by generating light-emitting diode (LED)-based displays, skin-mounted electronics, and stimulators that deliver localized current to in vitro neuron cultures and muscles in vivo with reduced adverse effects. Such electronic platforms may form the basis of future biointegrated electronic systems. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.

PubMed

Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; van Damme, Pierre

2016-10-17

Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biopharmaceutical Assessment and Irritation Potential of Microemulsions and Conventional Systems Containing Oil from Syagrus cearensis for Topical Delivery of Amphotericin B Using Alternative Methods.

PubMed

Sousa, Giovana D; Kishishita, Juliana; Aquino, Kátia A S; Presgrave, Octávio A F; Leal, Leila B; Santana, Davi P

2017-07-01

The aim of this study was to compare the biopharmaceutical characteristics and irritation potentials of microemulsions (MEs) and conventional systems (CSs) containing oil from Syagrus cearensis for topical delivery of Amphotericin B (AmB). Pseudo-ternary phase diagrams were constructed using a water titration method to develop the MEs, and the CSs were prepared according to the classical technique of phase inversion. In the skin permeation and retention study, dermatomed pig skin without stratum corneum was used as an alternative disturbed skin model. The irritation potential was evaluated using three different methods, chorioallantoic membrane assays (HET-CAM and CAM-TBS), and bovine corneal opacity and permeability (BCOP) test. The optimized formulation (ME1) consisting of 0.1% (w/w) Amphotericin B, 9.1% (w/w) catolé oil, 81% (w/w) Smix (1:1, Tween 20 and Kolliphor EL) possessed droplet size of 31.02 ± 0.9 nm, zeta potential of -23.4 mV, and viscosity 0.63 ± 0.1 Pa.s. ME1 exhibited greater retention of AmB in to skin layers (84.79 ± 2.08 μg cm -2 ) than all the others formulations. In general, MEs showed higher drug release and retention than CSs and all of the formulations showed greater retentivity than permeability. Only MEs developed using Labrasol/Plurol Oleique (L/PO) as the surfactant and co-surfactant exhibited a moderate irritation potential; all other MEs and CSs were classified as non-irritants or slight irritants. The results indicate that formulations containing oil from S. cearensis are promising alternatives for the delivery of AmB targeting the treatment of cutaneous leishmaniasis.

The impact of delivery style on doctors' experience of stress during simulated bad news consultations.

PubMed

Shaw, Joanne; Brown, Rhonda; Dunn, Stewart

2015-10-01

The purpose of this study was to investigate the relationship between doctors' bad news delivery style and their experience of physiological stress during simulated bad news consultations. 31 doctors participated in two simulated breaking bad news (BBN) consultations. Delivery style was categorized as either blunt, forecasting or stalling (i.e. avoidant), based on the time to deliver the bad news and qualitative analysis of the interaction content and doctor's language style. Doctors' heart rate (HR) and skin conductance (SC) were recorded in consecutive 30s epochs. Doctors experienced a significant decrease in HR (F(1,36)=44.9, p<.0001) and SC (F(1,48)=5.6, p<.001) between the pre- and post-news delivery phases of the consultation. Between-group comparisons for the three delivery styles did not identify any significant differences in HR (F(2,36)=2.2, p>.05) or SC (F(2,48)=.66, p>.05). Doctors experience heightened stress in the pre-news delivery phase of breaking bad news interactions. Delaying the delivery of bad news exposes doctors to a longer period of increased stress.This suggests that medical students and doctors should be taught to deliver bad news without delay, to help mitigate their response to this stressful encounter. Copyright © 2015. Published by Elsevier Ireland Ltd.

Synthesis, characterisation and phase transition behaviour of temperature-responsive physically crosslinked poly (N-vinylcaprolactam) based polymers for biomedical applications.

PubMed

Halligan, Shane C; Dalton, Maurice B; Murray, Kieran A; Dong, Yixiao; Wang, Wenxin; Lyons, John G; Geever, Luke M

2017-10-01

Poly (N-vinylcaprolactam) (PNVCL) is a polymer which offers superior characteristics for various potential medical device applications. In particular it offers unique thermoresponsive capabilities, which fulfils the material technology constraints required in targeted drug delivery applications. PNVCL phase transitions can be tailored in order to suit the requirements of current and next generation devices, by modifying the contents with regard to the material composition and aqueous polymer concentration. In this study, physically crosslinked Poly (N-vinylcaprolactam)-Vinyl acetate (PNVCL-VAc) copolymers were prepared by photopolymerisation. The structure of the polymers was established by Fourier transform infrared spectroscopy, nuclear magnetic resonance and gel permeation chromatography. The polymers were further characterised using differential scanning calorimetry and swelling studies. Determination of the LCST of the polymers in aqueous solution was achieved by employing four techniques; cloud point, UV-spectrometry, differential scanning calorimetry and rheometry. Sol-gel transition was established using tube inversion method and rheological analysis. This study was conducted to determine the characteristics of PNVCL with the addition of VAc, and to establish the effects on the phase transition. The PNVCL based polymers exhibited a decrease in the LCST as the composition of VAc increased. Sol-gel transition could be controlled by altering the monomeric feed ratio and polymer concentration in aqueous milieu. Importantly all copolymers (10wt% in solution) underwent gelation between 33.6 and 35.9°C, and based on this and the other materials properties recorded in this study, these novel copolymers have potential for use as injectable in situ forming drug delivery systems for targeted drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

"Catch the Pendulum": The Problem of Asymmetric Data Delivery in Electromagnetic Nanonetworks.

PubMed

Islam, Nabiul; Misra, Sudip

2016-09-01

The network of novel nano-material based nanodevices, known as nanoscale communication networks or nanonetworks has ushered a new communication paradigm in the terahertz band (0.1-10 THz). In this work, first we envisage an architecture of nanonetworks-based Coronary Heart Disease (CHD) monitoring, consisting of nano-macro interface (NM) and nanodevice-embedded Drug Eluting Stents (DESs), termed as nanoDESs. Next, we study the problem of asymmetric data delivery in such nanonetworks-based systems and propose a simple distance-aware power allocation algorithm, named catch-the-pendulum, which optimizes the energy consumption of nanoDESs for communicating data from the underlying nanonetworks to radio frequency (RF) based macro-scale communication networks. The algorithm exploits the periodic change in mean distance between a nanoDES, inserted inside the affected coronary artery, and the NM, fitted in the intercostal space of the rib cage of a patient suffering from a CHD. Extensive simulations confirm superior performance of the proposed algorithm with respect to energy consumption, packet delivery, and shutdown phase.

Enhanced Endosomal Escape by Light-Fueled Liquid-Metal Transformer.

PubMed

Lu, Yue; Lin, Yiliang; Chen, Zhaowei; Hu, Quanyin; Liu, Yang; Yu, Shuangjiang; Gao, Wei; Dickey, Michael D; Gu, Zhen

2017-04-12

Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal. When coated with graphene quantum dots (GQDs), the resulting nanospheres demonstrate the ability to absorb and convert photoenergy to drive the simultaneous phase separation and morphological transformation of the inner liquid-metal core. The morphological transformation from nanospheres to hollow nanorods with a remarkable change of aspect ratio can physically disrupt the endosomal membrane to promote endosomal escape of payloads. This metal-based nanotransformer equipped with GQDs provides a new strategy for facilitating effective endosomal escape to achieve spatiotemporally controlled drug delivery with enhanced efficacy.

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

An Evaluation of the AFIT Teleteach Expanded Delivery System (TEDS) Method of Instruction (Phase 1).

DTIC Science & Technology

1980-06-01

S-ce-s, and AMFT’s cwco classrocmns. By so odn.- the= exten ses, any cost.s dL:rectly atcUrL’utacle to A?:btshared by u~sers f"r A’LC and AFSC waere ...34 Audiovisual instruction, May 1971, pp. 85-86. O’Sullivan, Kevin . "Audio For Training and Development: Some Notes about the Medium," Training and

Design, fabrication, testing, and delivery of improved beam steering devices

NASA Technical Reports Server (NTRS)

1973-01-01

The development, manufacture, and testing of an optical steerer intended for use in spaceborne optical radar systems are described. Included are design principles and design modifications made to harden the device against launch and space environments, the quality program and procedures developed to insure consistent product quality throughout the manufacturing phase, and engineering qualification model testing and evaluation. The delivered hardware design is considered conditionally qualified pending action on further recommended design modifications.

The Plant Research Unit: An International Space Station Habitat

NASA Technical Reports Server (NTRS)

Morrow, Robert; Reiss-Bubenheim, Debra; Schaefer, Ronald L.

2003-01-01

The Plant Research Unit (PRU) is one of six life science habitats being developed as part of the Space Station Biological Research Program. The PRU is designed for experiments in microgravity and will utilize the ISS Centrifuge Facility to provide gravity levels between microgravity and 29. The PRU will provide and control all aspects of a plant s needs in a nearly closed system. In other words, the shoot and root environments will not be open to the astronaut s environment except for experiment maintenance such as planting, harvesting and plant sampling. This also means that all lighting, temperature and humidity control, "watering," and air filtering and cleaning .must be done within strict limitations of volume, weight, power, and crew time while at the same time providing a very high level of reliability and a service life in excess of 10 years. The PRU will contain two plant chambers 31.5 cm tall, each with independent control of temperature, humidity, light level and photoperiod, CO2 level, nutrient and water delivery, and video and data acquisition. The PRU is currently in the preliminary design phase and a number of subsystem components have been prototyped for testing, including the temperature and humidity control systems, the plant chambers, the LED lighting system, the atmospheric control system and a variety of nutrient delivery systems. The LED prototype provides independent feedback control of 5 separate spectral bands and variable output between 0 and 1000 micro-mol sq m/sec. The water and nutrient delivery system (WNDS) prototypes have been used to test particulate based, thin film, and gel-based WNDS configurations.

Effect of Moisture on the Thermoresponsive Properties of Binary Mixtures of Monoglycerides for Triggerable Drug Delivery Systems.

PubMed

Stonewall, Hannah D; Kessinger, Haley M; Mengesha, Abebe E

2017-10-01

The crystallization behavior and temperature-dependent phase transition of monoglycerides have been utilized to develop thermal-sensitive drug delivery systems. The presence of excess water has been reported to influence the phase transition. The present study investigates the effect of moisture on the thermal behavior of binary blends of monoglycerides. Various compositions (0-100 wt%) of glyceryl monooleate (GMO) and glyceryl monostearate (GMS) were prepared by fusion method, and exposed to varying relative humidity (RH) levels (0-100%). The moisture uptakes, sorption isotherm, and the thermal behavior of GMO-GMS samples were analyzed using differential scanning calorimeter (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The in vitro nifedipine (NF) release was studied at 37 and 42°C. Samples of GMO-GMS (25:75, 50:50, and 75:25 wt%) stored at 97%RH at 25°C for 3 weeks increased in weight by 14.0, 14.7, and 15.8%, respectively. Despite such high moisture uptake, the GMO-GMS matrices maintained crystalline structure. The melting point (T m ) and heat of fusion (ΔH f ) of the samples were reduced as the amount of moisture in the matrices increased. However, the heat of fusion calculated on dry basis remained constant at 139.4 ± 1.25, 102.7 ± 1.14, and 46.7 ± 1.16 J/g for GMO-GMS 25:75, 50:50, and 75:25 wt%, respectively. The comparison of the XRD measurements of the dry samples with those containing 30% water confirmed the preserved crystalline arrangement in the matrices. This study indicates that despite the high moisture uptakes, the GMO-GMS matrices retained their crystalline properties and provided temperature-dependent drug release indicating the potential application for thermoresponsive local drug delivery systems.

HIFU Monitoring and Control with Dual-Mode Ultrasound Arrays

NASA Astrophysics Data System (ADS)

Casper, Andrew Jacob

The biological effects of high-intensity focused ultrasound (HIFU) have been known and studied for decades. HIFU has been shown capable of treating a wide variety of diseases and disorders. However, despite its demonstrated potential, HIFU has been slow to gain clinical acceptance. This is due, in part, to the difficulty associated with robustly monitoring and controlling the delivery of the HIFU energy. The non-invasive nature of the surgery makes the assessment of treatment progression difficult, leading to long treatment times and a significant risk of under treatment. This thesis research develops new techniques and systems for robustly monitoring HIFU therapies for the safe and efficacious delivery of the intended treatment. Systems and algorithms were developed for the two most common modes of HIFU delivery systems: single-element and phased array applicators. Delivering HIFU with a single element transducer is a widely used technique in HIFU therapies. The simplicity of a single element offers many benefits in terms of cost and overall system complexity. Typical monitoring schemes rely on an external device (e.g. diagnostic ultrasound or MRI) to assess the progression of therapy. The research presented in this thesis explores using the same element to both deliver and monitor the HIFU therapy. The use of a dual-mode ultrasound transducer (DMUT) required the development of an FPGA based single-channel arbitrary waveform generator and high-speed data acquisition unit. Data collected from initial uncontrolled ablations led to the development of monitoring and control algorithms which were implemented directly on the FPGA. Close integration between the data acquisition and arbitrary waveform units allowed for fast, low latency control over the ablation process. Results are presented that demonstrate control of HIFU therapies over a broad range of intensities and in multiple in vitro tissues. The second area of investigation expands the DMUT research to an ultrasound phased-array. The phased-array allows for electronic steering of the HIFU focus and imaging of the acoustic medium. Investigating the dual-mode ultrasound array (DMUA) required the design and construction of a novel ultrasound-guided focused ultrasound (USgFUS) platform. The platform consisted of custom hardware designed for the unique requirements of operating a phased-array in both therapeutic and imaging modes. The platform also required the development of FPGA based signal processing and GPU based beamforming algorithms for online monitoring of the therapy process. The results presented in this thesis represent the first demonstration of a real-time USgFUS platform based around a DMUA. Experimental imaging and therapy results from series of animal experiments, including a 12 animal GLP study, are presented. In addition, in vitro control results, which build upon the DMUT work, are presented.

Water-in-Water Emulsion Based Synthesis of Hydrogel Nanospheres with Tunable Release Kinetics

NASA Astrophysics Data System (ADS)

Aydın, Derya; Kızılel, Seda

2017-07-01

Poly(ethylene glycol) (PEG) micro/nanospheres have several unique advantages as polymer based drug delivery systems (DDS) such as tunable size, large surface area to volume ratio, and colloidal stability. Emulsification is one of the widely used methods for facile synthesis of micro/nanospheres. Two-phase aqueous system based on polymer-polymer immiscibility is a novel approach for preparation of water-in-water (w/w) emulsions. This method is promising for the synthesis of PEG micro/nanospheres for biological systems, since the emulsion is aqueous and do not require organic solvents or surfactants. Here, we report the synthesis of nano-scale PEG hydrogel particles using w/w emulsions using phase separation of dextran and PEG prepolymer. Dynamic light scattering (DLS) and scaning electron microscopy (SEM) results demonstrated that nano-scale hydrogel spheres could be obtained with this approach. We investigated the release kinetics of a model drug, pregabalin (PGB) from PEG nanospheres and demonstrated the influence of polymerization conditions on loading and release of the drug as well as the morphology and size distribution of PEG nanospheres. The experimental drug release data was fitted to a stretched exponential function which suggested high correlation with experimental results to predict half-time and drug release rates from the model equation. The biocompatibility of nanospheres on human dermal fibroblasts using cell-survival assay suggested that PEG nanospheres with altered concentrations are non-toxic, and can be considered for controlled drug/molecule delivery.

ESO adaptive optics facility progress report

NASA Astrophysics Data System (ADS)

Arsenault, Robin; Madec, Pierre-Yves; Paufique, Jerome; La Penna, Paolo; Stroebele, Stefan; Vernet, Elise; Pirard, Jean-Francois; Hackenberg, Wolfgang; Kuntschner, Harald; Jochum, Lieselotte; Kolb, Johann; Muller, Nicolas; Le Louarn, Miska; Amico, Paola; Hubin, Norbert; Lizon, Jean-Louis; Ridings, Rob; Abad, Jose A.; Fischer, Gert; Heinz, Volker; Kiekebusch, Mario; Argomedo, Javier; Conzelmann, Ralf; Tordo, Sebastien; Donaldson, Robert; Soenke, Christian; Duhoux, Philippe; Fedrigo, Enrico; Delabre, Bernard; Jost, Andreas; Duchateau, Michel; Downing, Mark; Moreno, Javier R.; Dorn, Reinhold; Manescau, Antonio; Bonaccini Calia, Domenico; Quattri, Marco; Dupuy, Christophe; Guidolin, Ivan M.; Comin, Mauro; Guzman, Ronald; Buzzoni, Bernard; Quentin, Jutta; Lewis, Steffan; Jolley, Paul; Kraus, Maximilian; Pfrommer, Thomas; Biasi, Roberto; Gallieni, Daniele; Bechet, Clementine; Stuik, Remko

2012-07-01

The ESO Adaptive Optics Facility (AOF) consists in an evolution of one of the ESO VLT unit telescopes to a laser driven adaptive telescope with a deformable mirror in its optical train. The project has completed the procurement phase and several large structures have been delivered to Garching (Germany) and are being integrated (the AO modules GRAAL and GALACSI and the ASSIST test bench). The 4LGSF Laser (TOPTICA) has undergone final design review and a pre-production unit has been built and successfully tested. The Deformable Secondary Mirror is fully integrated and system tests have started with the first science grade thin shell mirror delivered by SAGEM. The integrated modules will be tested in stand-alone mode in 2012 and upon delivery of the DSM in late 2012, the system test phase will start. A commissioning strategy has been developed and will be updated before delivery to Paranal. A substantial effort has been spent in 2011-2012 to prepare the unit telescope to receive the AOF by preparing the mechanical interfaces and upgrading the cooling and electrical network. This preparation will also simplify the final installation of the facility on the telescope. A lot of attention is given to the system calibration, how to record and correct any misalignment and control the whole facility. A plan is being developed to efficiently operate the AOF after commissioning. This includes monitoring a relevant set of atmospheric parameters for scheduling and a Laser Traffic control system to assist the operator during the night and help/support the observing block preparation.

AIRTV: Broadband Direct to Aircraft

NASA Astrophysics Data System (ADS)

Sorbello, R.; Stone, R.; Bennett, S. B.; Bertenyi, E.

2002-01-01

Airlines have been continuously upgrading their wide-body, long-haul aircraft with IFE (in-flight entertainment) systems that can support from 12 to 24 channels of video entertainment as well as provide the infrastructure to enable in-seat delivery of email and internet services. This is a direct consequence of increased passenger demands for improved in-flight services along with the expectations that broadband delivery systems capable of providing live entertainment (news, sports, financial information, etc.) and high speed data delivery will soon be available. The recent events of Sept. 11 have slowed the airline's upgrade of their IFE systems, but have also highlighted the compelling need for broadband aeronautical delivery systems to include operational and safety information. Despite the impact of these events, it is estimated that by 2005 more than 3000 long haul aircraft (servicing approximately 1 billion passengers annually) will be fully equipped with modern IFE systems. Current aircraft data delivery systems, which use either Inmarsat or NATS, are lacking in bandwidth and consequently are unsuitable to satisfy passenger demands for broadband email/internet services or the airlines' burgeoning data requirements. Present live video delivery services are limited to regional coverage and are not readily expandable to global or multiregional service. Faced with a compelling market demand for high data transport to aircraft, AirTV has been developing a broadband delivery system that will meet both passengers' and airlines' needs. AirTV is a global content delivery system designed to provide a range of video programming and data services to commercial airlines. When AirTV is operational in 2004, it will provide a broadband connection directly to the aircraft, delivering live video entertainment, internet/email service and essential operational and safety data. The system has been designed to provide seamless global service to all airline routes except for those over the poles. The system consists of a constellation of 4 geostationary satellites covering the earth and delivering its signals to the aircraft at S band (2.52 -2.67 GHz). The S-band spectrum is ideal for this application since it is allocated on a primary basis by the ITU for global broadcast service. The AirTV service is expected to begin in 2004 and should be unencumbered by adjacent satellite interference due to near completion of the ITU coordination process. Each satellite will deliver four 20 Mbps QPSK data streams consisting of multiplexed compressed digital video channels and IP data over the full global beam coverage. The 80 Mbps capacity of each satellite will provide approximately 60 video channels while still allocating 40 Mbits to data services. The combined constellation capacity of 320 Mbits will significantly exceed the capacity of any similar existing or currently planned global satellite system. In addition, the simplicity of the 4-satellite approach is the most cost effective means to deliver high bandwidth globally. Return links, which are required for internet service, will be provided through the existing Inmarsat Aero-H system already onboard virtually all long haul aircraft and will provide return data rates from the aircraft as high as 432 kbps. integrated receiver/decoder (IRD) assembly. The phased array antenna, a key technology element, is being developed by AirTV's strategic partner, CMC Electronics. This antenna is a scaled version of CMC's Inmarsat Aero H antenna and is capable of scanning to 5 degrees above the horizon. Wide angle scanning up to 85 degrees from zenith is necessary for aircraft traversing the northernmost latitudes on transoceanic routes. AirTV has designed both the satellite coverage and aircraft antenna performance to ensure that high signal quality is maintained along all non-polar airline routes. AirTV will be the future of aeronautical broadband delivery. It has been designed specifically for global services and uses the ideal spectrum for this application. It will revolutionize the delivery of content to aircraft. This paper will describe the AirTV system and highlight its advanced service capabilities.

Utilization of nanoemulsions to enhance bioactivity of pharmaceuticals, supplements, and nutraceuticals: Nanoemulsion delivery systems and nanoemulsion excipient systems.

PubMed

Aboalnaja, Khaled Omer; Yaghmoor, Soonham; Kumosani, Taha Abdullah; McClements, David Julian

2016-09-01

The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

Effect of chronic delivery of the Toll-like receptor 4 antagonist (+)-Naltrexone on incubation of heroin craving

PubMed Central

Theberge, Florence R.; Li, Xuan; Kambhampati, Sarita; Pickens, Charles L.; St. Laurent, Robyn; Bossert, Jennifer M.; Baumann, Michael H.; Hutchinson, Mark R.; Rice, Kenner C.; Watkins, Linda R.; Shaham, Yavin

2013-01-01

Background Recent evidence implicates toll-like receptor 4 (TLR4) in opioid analgesia, tolerance, conditioned place preference, and self-administration. Here we determined the effect of the TLR4 antagonist (+)-naltrexone (a μ-opioid receptor inactive isomer) on the time-dependent increases in cue-induced heroin seeking after withdrawal (incubation of heroin craving). Methods In an initial experiment, we trained rats for 9 h/day to self-administer heroin (0.1 mg/kg/infusion) for 9 days; lever presses were paired with a 5-sec tone-light cue. We then assessed cue-induced heroin seeking in 30-min extinction sessions on withdrawal day 1; immediately after testing, we surgically implanted rats with Alzet minipumps delivering (+)-naltrexone (0, 7.5, 15, 30 mg/kg/day, s.c.) for 14 days. We then tested the rats for incubated cue-induced heroin seeking in 3-h extinction tests on withdrawal day 13. Results We found that chronic delivery of (+)-naltrexone via minipumps during the withdrawal phase decreased incubated cue-induced heroin seeking. In follow-up experiments, we found that acute injections of (+)-naltrexone immediately before withdrawal day 13 extinction test had no effect on incubated cue-induced heroin seeking. Furthermore, chronic delivery of (+)-naltrexone (15 or 30 mg/kg/day) or acute systemic injections (15 or 30 mg/kg) had no effect on ongoing extended access heroin self-administration. Finally, in rats trained to self-administer methamphetamine (0.1 mg/kg/infusion, 9 h/d, 9 days), chronic delivery of (+)-naltrexone (30 mg/kg/day) during the withdrawal phase had no effect on incubated cue-induced methamphetamine seeking. Conclusions The present results suggest a critical role of TLR4 in the development of incubation of heroin, but not methamphetamine, craving. PMID:23384483

Development and effect of different bioactive silicate glass scaffolds: in vitro evaluation for use as a bone drug delivery system.

PubMed

Soundrapandian, Chidambaram; Mahato, Arnab; Kundu, Biswanath; Datta, Someswar; Sa, Biswanath; Basu, Debebrata

2014-12-01

Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO2-Na2O-ZnO-CaO-MgO-P2O5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63-66% porous and 5-50μm almost unimodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas-Korsmeyer release pattern based on Fickian diffusion, while 0.5-1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain and confirm the cytotoxic nature and wound healing potential of this glass. Copyright © 2014 Elsevier Ltd. All rights reserved.

Determination of in vivo behavior of mitomycin C-loaded o/w soybean oil microemulsion and mitomycin C solution via gamma camera imaging.

PubMed

Kotmakçı, Mustafa; Kantarcı, Gülten; Aşıkoğlu, Makbule; Ozkılıç, Hayal; Ertan, Gökhan

2013-09-01

In this study, a microemulsion system was evaluated for delivery of mitomycin C (MMC). To track the distribution of the formulated drug after intravenous administration, radiochemical labeling and gamma scintigraphy imaging were used. The aim was to evaluate a microemulsion system for intravenous delivery of MMC and to compare its in vivo behavior with that of the MMC solution. For microemulsion formulation, soybean oil was used as the oil phase. Lecithin and Tween 80 were surfactants and ethanol was the cosurfactant. To understand the whole body localization of MMC-loaded microemulsion, MMC was labeled with radioactive technetium and gamma scintigraphy was applied for visualization of drug distribution. Radioactivity in the bladder 30 minutes after injection of the MMC solution was observed, according to static gamma camera images. This shows that urinary excretion of the latter starts very soon. On the other hand, no radioactivity appeared in the urinary bladder during the 90 minutes following the administration of MMC-loaded microemulsion. The unabated radioactivity in the liver during the experiment shows that the localization of microemulsion formulation in the liver is stable. In the light of the foregoing, it is suggested that this microemulsion formulation may be an appropriate carrier system for anticancer agents by intravenous delivery in hepatic cancer chemotherapy.

Influence of protoporphyrin IX loaded phloroglucinol succinic acid dendrimer in photodynamic therapy

NASA Astrophysics Data System (ADS)

Kumar, M. Suresh; Aruna, P.; Ganesan, S.

2018-03-01

One of the major problems reported clinically for photosensitizers (PS) in Photodynamic therapy (PDT) is, the cause of side-effects to normal tissue due to dark toxicity. The usefulness of photosensitizers can be made possible by reducing its dark toxicity nature. In such scenario, biocompatible carriers can be used as a drug delivery system to evade the problems that arises while using free (dark toxic) drugs. So in this study, we have developed a nano drug delivery system called Phloroglucinol Succinic acid (PGSA) dendrimer, entrapped a photosensitizer, protoporphyrin IX (PpIX) inside the system and investigated whether the photodynamic efficacy of the anionic surface charged dendrimer-PpIX nano formulation is enhanced than achieved by the free PpIX in HeLa cancer cell lines. Moreover, the Reactive oxygen species (ROS) production was monitored using 2‧,7‧-dichlorodihydrofluorescein diacetate (H2DCF-DA)- ROS Marker with phase contrast microscopy for the IC50 values of free and dendrimer-PpIX nano formulation. Similarly, the mode of cell death has been confirmed by cell cycle analysis for the same. For the in vitro PDT application, we have used a simple light source (Light Emitting Diode) with a power of 30-50 mW for 20 min irradiation. Hence, in this study we have taken steps to report this anionic drug delivery system is good to consider for the photodynamic therapy applications with the photosensitizer, PpIX which satisfied the prime requirement of PDT.

Elastin-like polypeptide matrices for enhancing adeno-associated virus-mediated gene delivery to human neural stem cells.

PubMed

Kim, J-S; Chu, H S; Park, K I; Won, J-I; Jang, J-H

2012-03-01

The successful development of efficient and safe gene delivery vectors continues to be a major obstacle to gene delivery in stem cells. In this study, we have developed an elastin-like polypeptide (ELP)-mediated adeno-associated virus (AAV) delivery system for transducing fibroblasts and human neural stem cells (hNSCs). AAVs have significant promise as therapeutic vectors because of their safety and potential for use in gene targeting in stem cell research. ELP has been recently employed as a biologically inspired 'smart' biomaterial that exhibits an inverse temperature phase transition, thereby demonstrating promise as a novel drug carrier. The ELP that was investigated in this study was composed of a repetitive penta-peptide with [Val-Pro-Gly-Val-Gly]. A novel AAV variant, AAV r3.45, which was previously engineered by directed evolution to enhance transduction in rat NSCs, was nonspecifically immobilized onto ELPs that were adsorbed beforehand on a tissue culture polystyrene surface (TCPS). The presence of different ELP quantities on the TCPS led to variations in surface morphology, roughness and wettability, which were ultimately key factors in the modulation of cellular transduction. Importantly, with substantially reduced viral quantities compared with bolus delivery, ELP-mediated AAV delivery significantly enhanced delivery efficiency in fibroblasts and hNSCs, which have great potential for use in tissue engineering applications and neurodegenerative disorder treatments, respectively. The enhancement of cellular transduction in stem cells, as well as the feasibility of ELPs for utilization in three-dimensional scaffolds, will contribute to the advancement of gene therapy for stem cell research and tissue regenerative medicine.

Delivery of Vaccines By Biodegradable Polymeric Microcapsules with Bioadherence Properties. Phase 1.

DTIC Science & Technology

1995-10-01

DAMD17-95-C-5061 TITLE: Delivery of Vaccines by Biodegradable Polymeric Microcapsules with Bioadherence Properties PRINCIPAL INVESTIGATOR: Robert L...SUBTITLE 5. FUNDING NUMBERS Delivery of Vaccines By Biodegradable Polymeric Microcapsules with Bioadherence Properties DAMD17-95-C-5061 6. AUTHOR(S...SUBJECT TERMS 15. NUMBER OF PAGES Polymer microspheres 27 Microencapsulated vaccines 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY

Clinical Considerations of Focal Drug Delivery in Cancer Treatment.

PubMed

Harris, Jamie; Klonoski, Samuel C; Chiu, Bill

2017-01-01

According to the US Center for Disease Control, cancer deaths are the second most common cause of mortality in both adults and children. Definitive treatment of solid tumors involves surgical resection with or without systemic chemotherapy and radiation. The advent of local drug delivery presents a unique treatment modality that can offer substantial benefits in cancer management. Three main phases in solid tumor management exist for the treating physician: initial diagnosis with tissue biopsy, surgical resection with or without chemotherapy, and management of metastatic disease. A literature review of both basic science as well as clinical trials using local drug delivery strategies in the management of solid tumors was done on PubMed. These were then further divided into the categories of initial tissue biopsy intervention, surgical resection, and management of metastatic disease. A total of 27 articles were review that included both pre-clinical as well as clinical investigation of local drug delivery therapies in the treatment of solid tumors. Treatments such as MRI guided therapies, FDA approved local therapies for intracranial gliomas as well as local therapy for single site metastatic disease were identified. This review focuses the current state of local drug delivery in the treatment of solid tumors in both the pre-clinical as well as clinical investigation settings. Local drug delivery therapy offers an exciting new treatment modality for solid malignancies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Novel devices for solvent delivery and temperature programming designed for capillary liquid chromatography.

PubMed

Coutinho, Lincoln Figueira Marins; Nazario, Carlos Eduardo Domingues; Monteiro, Alessandra Maffei; Lanças, Fernando Mauro

2014-08-01

Analyses in chromatographic systems able to save mobile and stationary phases without reducing efficiency and resolution are of current interest. These advantages regarding savings have challenged us to develop a system dedicated to miniaturized liquid chromatography. This paper reports on the development of a high-pressure syringe-type pump, an oven able to perform isothermal and temperature programming and a software program to control these chromatographic devices. The experimental results show that the miniaturized system can generate reproducible and accurate temperature and flow rate. The system was applied to the separation of statins and tetracylines and showed excellent performance. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

40-Gb/s PDM-QPSK signal transmission over 160-m wireless distance at W-band.

PubMed

Xiao, Jiangnan; Yu, Jianjun; Li, Xinying; Xu, Yuming; Zhang, Ziran; Chen, Long

2015-03-15

We experimentally demonstrate a W-band optical-wireless transmission system over 160-m wireless distance with a bit rate up to 40 Gb/s. The optical-wireless transmission system adopts optical polarization-division-multiplexing (PDM), multiple-input multiple-output (MIMO) reception and antenna polarization diversity. Using this system, we experimentally demonstrate the 2×2 MIMO wireless delivery of 20- and 40-Gb/s PDM quadrature-phase-shift-keying (PDM-QPSK) signals over 640- and 160-m wireless links, respectively. The bit-error ratios (BERs) of these transmission systems are both less than the forward-error-correction (FEC) threshold of 3.8×10^-3.

Management assessment of tank waste remediation system contractor readiness to proceed with phase 1B privatization

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

Certa, P.J.

1998-01-07

Readiness to Proceed With Phase 1B Privatization documents the processes used to determine readiness to proceed with tank waste treatment technologies from private industry, now known as TWRS privatization. An overall systems approach was applied to develop action plans to support the retrieval and disposal mission of the TWRS Project. The systems and infrastructure required to support the mission are known. Required systems are either in place or plans have been developed to ensure they exist when needed. Since October 1996 a robust system engineering approach to establishing integrated Technical Baselines, work breakdown structures, tank farms organizational structure and configurations,more » work scope, and costs has become part of the culture within the TWRS Project. An analysis of the programmatic, management, and technical activities necessary to declare readiness to proceed with execution of the mission demonstrates that the system, personnel, and hardware will be on line and ready to support the private contractors. The systems approach included defining the retrieval and disposal mission requirements and evaluating the readiness of the Project Hanford Management Contract (PHMC) team to support initiation of waste processing by the private contractors in June 2002 and to receive immobilized waste shortly thereafter. The Phase 1 feed delivery requirements from the private contractor Requests for Proposal were reviewed. Transfer piping routes were mapped, existing systems were evaluated, and upgrade requirements were defined.« less

Anti-CD22 Antibody Targeting of pH-responsive Micelles Enhances Small Interfering RNA Delivery and Gene Silencing in Lymphoma Cells

PubMed Central

Palanca-Wessels, Maria C; Convertine, Anthony J; Cutler-Strom, Richelle; Booth, Garrett C; Lee, Fan; Berguig, Geoffrey Y; Stayton, Patrick S; Press, Oliver W

2011-01-01

The application of small interfering RNA (siRNA) for cancer treatment is a promising strategy currently being explored in early phase clinical trials. However, efficient systemic delivery limits clinical implementation. We developed and tested a novel delivery system comprised of (i) an internalizing streptavidin-conjugated monoclonal antibody (mAb-SA) directed against CD22 and (ii) a biotinylated diblock copolymer containing both a positively charged siRNA condensing block and a pH-responsive block to facilitate endosome release. The modular design of the carrier facilitates the exchange of different targeting moieties and siRNAs to permit its usage in a variety of tumor types. The polymer was synthesized using the reversible addition fragmentation chain transfer (RAFT) technique and formed micelles capable of binding siRNA and mAb-SA. A hemolysis assay confirmed the predicted membrane destabilizing activity of the polymer under acidic conditions typical of the endosomal compartment. Enhanced siRNA uptake was demonstrated in DoHH2 lymphoma and transduced HeLa-R cells expressing CD22 but not in CD22 negative HeLa-R cells. Gene knockdown was significantly improved with CD22-targeted vs. nontargeted polymeric micelles. Treatment of DoHH2 cells with CD22-targeted polymeric micelles containing 15 nmol/l siRNA produced 70% reduction of gene expression. This CD22-targeted polymer carrier may be useful for siRNA delivery to lymphoma cells. PMID:21629223

Anti-CD22 antibody targeting of pH-responsive micelles enhances small interfering RNA delivery and gene silencing in lymphoma cells.

PubMed

Palanca-Wessels, Maria C; Convertine, Anthony J; Cutler-Strom, Richelle; Booth, Garrett C; Lee, Fan; Berguig, Geoffrey Y; Stayton, Patrick S; Press, Oliver W

2011-08-01

The application of small interfering RNA (siRNA) for cancer treatment is a promising strategy currently being explored in early phase clinical trials. However, efficient systemic delivery limits clinical implementation. We developed and tested a novel delivery system comprised of (i) an internalizing streptavidin-conjugated monoclonal antibody (mAb-SA) directed against CD22 and (ii) a biotinylated diblock copolymer containing both a positively charged siRNA condensing block and a pH-responsive block to facilitate endosome release. The modular design of the carrier facilitates the exchange of different targeting moieties and siRNAs to permit its usage in a variety of tumor types. The polymer was synthesized using the reversible addition fragmentation chain transfer (RAFT) technique and formed micelles capable of binding siRNA and mAb-SA. A hemolysis assay confirmed the predicted membrane destabilizing activity of the polymer under acidic conditions typical of the endosomal compartment. Enhanced siRNA uptake was demonstrated in DoHH2 lymphoma and transduced HeLa-R cells expressing CD22 but not in CD22 negative HeLa-R cells. Gene knockdown was significantly improved with CD22-targeted vs. nontargeted polymeric micelles. Treatment of DoHH2 cells with CD22-targeted polymeric micelles containing 15 nmol/l siRNA produced 70% reduction of gene expression. This CD22-targeted polymer carrier may be useful for siRNA delivery to lymphoma cells.

A novel intranasal breath-powered delivery system for sumatriptan: a review of technology and clinical application of the investigational product AVP-825 in the treatment of migraine.

PubMed

Cady, Roger

2015-01-01

AVP-825, formerly 'OptiNose Sumatriptan,' is an investigational Breath-Powered(TM) Bi-Directional(TM) intranasal delivery system containing low-dose sumatriptan (22 mg intranasal powder) that avoids limitations of other types of intranasal administration by taking advantage of unique features of nasal anatomy and physiology. This review summarizes intranasal drug delivery for migraine, how the breath-powered technology works, and AVP-825 pharmacokinetic, efficacy and safety/tolerability findings. To identify AVP-825 clinical studies, a PubMed/MEDLINE database search was conducted with the terms AVP-825, OptiNose, OptiNose Sumatriptan, Breath-Powered Nasal Delivery or sumatriptan powder. Of 20 articles, 5 clinical studies were identified, including the head-to-head comparative COMPASS trial (AVP-825 vs oral sumatriptan) and two placebo-controlled studies. AVP-825 has faster sumatriptan absorption versus oral tablets or traditional liquid nasal spray. In Phase II/III randomized, double-blind, placebo-controlled trials, AVP-825 produced early and sustained efficacy with minimal triptan-related adverse effects. In COMPASS, AVP-825 produced earlier reduction of migraine pain intensity and migraine-associated symptoms than 100 mg oral sumatriptan, and higher early rates of pain relief and pain freedom, similar sustained efficacy, and fewer atypical sensations. AVP-825 has the potential to provide migraine patients with improved intranasal administration of sumatriptan that may enhance efficacy and tolerability.

Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone.

PubMed

Gadalla, Hytham H; Soliman, Ghareb M; Mohammed, Fergany A; El-Sayed, Ahmed M

2016-09-01

The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (∼25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 µm were obtained. Drug entrapment efficiency of ∼75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ∼168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.

Experiment definition phase shuttle laboratory. LDRL-10.6 experiment

NASA Technical Reports Server (NTRS)

1976-01-01

The work completed on the experiment definition phase of the shuttle laboratory LDRL 10.6 micrometers experiment from 27 September 1975 to 26 January 1976 was reported. This work included progress in the following areas: (1) optomechanical system: completion of detail drawings, completion of the beryllium subassembly, fabrication, checking, and weighing of approximately 95% of the detailed parts, dry film lubrication of the bearings and gears, and initiation of assembly of the gimbals; (2) optics: update of the detailed optical layout, receipt of nine mirrors and the pre-expander; (3) miscellaneous: delivery of draft material for the final report, completion of optical testing of the 10.6 micrometers receiver, and receipt, assembly, and checkout of NASA test console.

Systematic development of design of experiments (DoE) optimised self-microemulsifying drug delivery system of Zotepine.

PubMed

Dalvadi, Hitesh; Patel, Nikita; Parmar, Komal

2017-05-01

The aim of present investigation is to improve dissolution rate of poor soluble drug Zotepine by a self-microemulsifying drug delivery system (SMEDDS). Ternary phase diagram with oil (Oleic acid), surfactant (Tween 80) and co-surfactant (PEG 400) at apex were used to identify the efficient self-microemulsifying region. Box-Behnken design was implemented to study the influence of independent variables. Principal Component Analysis was used for scrutinising critical variables. The liquid SMEDDS were characterised for macroscopic evaluation, % Transmission, emulsification time and in vitro drug release studies. Optimised formulation OL1 was converted in to S-SMEDDS by using Aerosil ® 200 as an adsorbent in the ratio of 3:1. The S-SMEDDS was characterised by SEM, DSC, globule size (152.1 nm), zeta-potential (-28.1 mV), % transmission study (98.75%), in vitro release (86.57%) at 30 min. The optimised solid SMEDDS formulation showed faster drug release properties as compared to conventional tablet of Zotepine.

Curcumin Protects Skin against UVB-Induced Cytotoxicity via the Keap1-Nrf2 Pathway: The Use of a Microemulsion Delivery System.

PubMed

Ben Yehuda Greenwald, Maya; Frušić-Zlotkin, Marina; Soroka, Yoram; Ben Sasson, Shmuel; Bitton, Ronit; Bianco-Peled, Havazelet; Kohen, Ron

2017-01-01

Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf 2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases.

Curcumin Protects Skin against UVB-Induced Cytotoxicity via the Keap1-Nrf2 Pathway: The Use of a Microemulsion Delivery System

PubMed Central

Ben Yehuda Greenwald, Maya; Frušić-Zlotkin, Marina; Soroka, Yoram; Ben Sasson, Shmuel; Bitton, Ronit; Bianco-Peled, Havazelet

2017-01-01

Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases. PMID:28757910

Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

PubMed Central

Rashid, Rehmana; Kim, Dong Wuk; Yousaf, Abid Mehmood; Mustapha, Omer; Din, Fakhar ud; Park, Jong Hyuck; Yong, Chul Soon; Oh, Yu-Kyoung; Youn, Yu Seok; Kim, Jong Oh; Choi, Han-Gon

2015-01-01

Background The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. Methods For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder. Results The drug existed in the crystalline form in SMSD, but was changed into an amorphous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 µm, respectively. All of these formulations significantly improved the aqueous solubility and dissolution in the order of solid SNEDDS ≥ SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability. Conclusion Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility. PMID:26491288

Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 2(3) factorial design and in vivo evaluation in rabbits.

PubMed

Soliman, Sara M; Abdelmalak, Nevine S; El-Gazayerly, Omaima N; Abdelaziz, Nabaweya

2016-06-01

Proniosomes offer a versatile vesicle drug delivery concept with potential for delivery of drugs via transdermal route. To develop proniosomal gel using cremophor RH 40 as non-ionic surfactant containing the antihypertensive drug lacidipine for transdermal delivery so as to avoid its extensive first pass metabolism and to improve its permeation through the skin. Proniosomes containing 1% lacidipine were prepared by the coacervation phase separation method, characterized, and optimized using a 2(3) full factorial design to define the optimum conditions to produce proniosomes with high entrapment efficiency, minimal vesicle size, and high-percentage release efficiency. The amount of cholesterol (X1), the amount of soya lecithin (X2), and the amount of cremophor RH 40 (X3) were selected as three independent variables. The system F4 was found to fulfill the maximum requisite of an optimum system because it had minimum vesicle size, maximum EE, maximum release efficiency, and maximum desirability. The optimized system (F4) was then converted to proniosomal gel using carbopol 940 (1% w/w). In vitro permeation through excised rabbit skin study revealed higher flux (6.48 ± 0.45) for lacidipine from the optimized proniosomal gel when compared with the corresponding emulgel (3.04 ± 0.13) mg/cm(2)/h. The optimized formulation was evaluated for its bioavailability compared with commercial product. Statistical analysis revealed significant increase in AUC (0 - α) 464.17 ± 113.15 ng h/ml compared with 209.02 ± 47.35 ng h/ml for commercial tablet. Skin irritancy and histopathological investigation of rat skin revealed its safety. Cremophor RH 40 proniosomal gel could be considered as very promising nanocarriers for transdermal delivery of lacidipine.

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.

Programmable Matter Creating Systems that Can Think, Talk, and Morph Autonomously. Phase 2

DTIC Science & Technology

2011-09-13

irradiation. SWNTs have a well-defined near-IR optical absorption, specifically ideal for biocompatible devices such as drug delivery mediums or biological...investigated as follows: • Lower Critical Transition Temperature(LCST) of the CNT-pNIPAM composites. • Strain change of CNT-pNIPAM hydrogel at LCST...loading at concentrations of 0.75mg/mL, we demonstrate up to 5 times enhancement to the thermal response time of the nanotube- pNIPAM hydrogel

Analytical Support, Characterization, and Optimization of a Canine Training Aid Delivery System: Phase 2

DTIC Science & Technology

2016-01-29

Arlington, Virginia 22203-1995 61-9496-A-2-5 ONR May 2014 – April 2015 *Nova Research, Inc., Alexandria, VA Improvised explosive device Detector dog Canine...37 Figure 30. Mass of MeS collected from three subsequent mock dog sniffs above the MODD. .. 37 Figure 31. Vapor concentration...particularly for the detection of HMEs. In 2012, the Office of Naval Research deployed as many as 280 IED Detector Dogs (IDDs) to Afghanistan [1

Antitumor effect of fibrin glue containing temozolomide against malignant glioma

PubMed Central

Anai, Shigeo; Hide, Takuichiro; Takezaki, Tatsuya; Kuroda, Jun-ichiro; Shinojima, Naoki; Makino, Keishi; Nakamura, Hideo; Yano, Shigetoshi; Kuratsu, Jun-ichi

2014-01-01

Temozolomide (TMZ), used to treat glioblastoma and malignant glioma, induces autophagy, apoptosis and senescence in cancer cells. We investigated fibrin glue (FG) as a drug delivery system for the local administration of high-concentration TMZ aimed at preventing glioma recurrence. Our high-power liquid chromatography studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug release potential. We prepared a subcutaneous tumor model by injecting groups of mice with three malignant glioma cell lines and examined the antitumor effect of TMZ-FG. We estimated the tumor volume and performed immunostaining and immunoblotting using antibodies to Ki-67, cleaved caspase 3, LC3 and p16. When FG sheets containing TMZ (TMZ-FGS) were inserted beneath the tumors, their growth was significantly suppressed. In mice treated with peroral TMZ plus TMZ-FGS the tumors tended to be smaller than in mice whose tumors were treated with TMZ-FGS or peroral TMZ alone. The TMZ-FGS induced autophagy, apoptosis and senescence in subcutaneous glioma tumor cells. To assess the safety of TMZ-FG for normal brain, we placed it directly on the brain of living mice and stained tissue sections obtained in the acute and chronic phase immunohistochemically. In both phases, TMZ-FG failed to severely damage normal brain tissue. TMZ-FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma. PMID:24673719

Technology evaluation: VEGF165 gene therapy, Valentis Inc.

PubMed

Morse, M A

2001-02-01

Valentis Inc, formerly GeneMedicine, is developing a vascular endothelial growth factor (VEGF165) non-viral gene therapy using its proprietary PINC polymer for plasmid condensation. Two physician-initiated phase II angioplasty trials are ongoing, one for treating peripheral vascular disease and one for treating coronary artery disease [281714], [347153]. In February 2000, the trials were expected to be completed in the fourth quarter of 2000 [356225]; however, in October 2000, it was reported that the trial for peripheral vascular disease would be completed in the first quarter of 2001 [385232]. In March 2000, Valentis initiated a trial incorporating Valentis's DOTMA-based cationic lipid gene delivery system and the VEGF165 gene with Eurogene's local collar-reservoir delivery device. The trial is designed to demonstrate that the VEGF165 gene, delivered locally to the outside surface of a blood vessel, will transfect and express in the smooth muscle cells of the vessel wall [360683]. In March 1999, Valentis was awarded with a Phase II SBIR grant of $686,260. The aim of grant was to advance the development of non-viral gene therapies for ischemia. Specifically, Valentis intended to select an optimal promoter to be used with the VEGF expression plasmid. Valentis also intended to evaluate the gene therapy system in a rabbit ischemia model and complete the necessary preclinical studies for submission of an IND [318137].

Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine

PubMed Central

Chintalapudi, Ramprasad; Murthy, T. E. G. K.; Lakshmi, K. Rajya; Manohar, G. Ganesh

2015-01-01

Background: The aim of the present study was to formulate and optimize the self-emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 22 factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation. Materials and Methods: Solubility of NVP in different oils, surfactants, and co-surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 22 factorial designs. Results: The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP. Conclusion: Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology. PMID:26682191

Development of a Predictive Model for the Stabilizer Concentration Estimation in Microreservoir Transdermal Drug Delivery Systems Using Lipophilic Pressure-Sensitive Adhesives as Matrix/Carrier.

PubMed

Chenevas-Paule, Clémence; Wolff, Hans-Michael; Ashton, Mark; Schubert, Martin; Dodou, Kalliopi

2017-05-01

Microreservoir-type transdermal drug delivery systems (MTDDS) can prevent drug crystallization; however, no current predictive model considers the impact of drug load and hydration on their physical stability. We investigated MTDDS films containing polyvinylpyrrolidone (PVP) as polymeric drug stabilizer in lipophilic pressure-sensitive adhesive (silicone). Medicated and unmedicated silicone films with different molar N-vinylpyrrolidone:drug ratios were prepared and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, microscopy, dynamic vapor sorption (DVS), and stability testing for 4 months at different storage conditions. Homogeneously distributed drug-PVP associates were observed when nonaqueous emulsions, containing drug-PVP (inner phase) and silicone adhesive (outer phase), were dried to films. DVS data were essential to predict physical stability at different humidities. A predictive thermodynamic model was developed based on drug-polymer hydrogen-bonding interactions, using the Hoffman equation, to estimate the drug-PVP ratio needed to obtain stable MTDDS and to evaluate the impact of humidity on their physical stability. This new approach considers the impact of polymorphism on drug solubility by using easily accessible experimental data (T m and DVS) and avoids uncertainties associated with the solubility parameter approach. In conclusion, a good fit of predicted and experimental data was observed. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Microfog lubricant application system for advanced turbine engine components, phase 3. [wetting characteristics and deposit forming tendencies of lubricants

NASA Technical Reports Server (NTRS)

Petrucco, R. J.; Leonardi, S. J.

1973-01-01

The wetting characteristics and deposit forming tendencies of a series of lubricants were evaluated using a microfog jet delivery system to wet a flat heated rotating disc. The performances of the nine lubricants are discussed in terms of the various testing parameters which include temperature, disc speed and lubricant gas flow rates. Also discussed are the heat transfer characteristics of two of the lubricants on that same plane disc specimen. The wetting characteristics and heat transfer characteristics of one of the lubricants on a complex disc simulating bearing geometry are also discussed.

Development of high-power dye laser chain

NASA Astrophysics Data System (ADS)

Konagai, Chikara; Kimura, Hironobu; Fukasawa, Teruichiro; Seki, Eiji; Abe, Motohisa; Mori, Hideo

2000-01-01

Copper vapor laser (CVL) pumped dye laser (DL) system, both in a master oscillator power amplifier (MOPA) configuration, has been developed for Atomic Vapor Isotope Separation program in Japan. Dye laser output power of about 500 W has been proved in long-term operations over 200 hours. High power fiber optic delivery system is utilized in order to efficiently transport kilowatt level CVL beams to the DL MOPA. Single model CVL pumped DL oscillator has been developed and worked for 200 hours within +/- 0.1 pm wavelength stability. Phase modulator for spreading spectrum to the linewidth of hyperfine structure has been developed and demonstrated.

Screening for Behavioral Risk Factors Is Not Enough to Improve Preventive Services Delivery.

PubMed

Drouin, Olivier; Winickoff, Jonathan P

Unhealthy behaviors are a major cause of chronic disease. Preappointment screening has been suggested as one way to improve preventive care delivery related to these behaviors by specifying risks to be addressed. We aimed to determine whether screening for health-related behaviors before the clinical encounter will lead to higher counseling rate and service delivery by clinicians. We used a pre/post design in one practice with a control practice to evaluate the effects of preappointment screening for 3 behavioral risk factors (tobacco smoke exposure, no recent dental care visit, and consumption of sugar-sweetened beverages). After their clinic visit, we asked English-speaking parents whose child had one or more risk factor whether they had received counseling or services from their pediatrician to address them. We recruited 264 parents in the pre phase and 242 in the post phase. Among 215 parents whose child had one or more risk factors, parents in the post phase were as likely to report receiving counseling than parents in the pre phase for each of the risk factors: smoking odds ratio 6.75 (95% confidence interval, 0.51, 88.88), dental health odds ratio 1.44 (95% confidence interval, 0.47, 4.41), and sugar-sweetened beverage consumption odds ratio 0.34 (95% confidence interval, 0.23, 5.18). Service delivery and reported behavior change were also similar in both phases. Counseling rates for tobacco, dental health, or sugar-sweetened beverage consumption were low in pediatric primary care, and preappointment screening did not significantly affect clinician counseling. Future efforts will require a more robust approach to effect change in counseling, provision of service, and family behavior. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Fast BPM data distribution for global orbit feedback using commercial gigabit ethernet technology

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

Hulsart, R.; Cerniglia, P.; Michnoff, R.

2011-03-28

In order to correct beam perturbations in RHIC around 10Hz, a new fast data distribution network was required to deliver BPM position data at rates several orders of magnitude above the capability of the existing system. The urgency of the project limited the amount of custom hardware that could be developed, which dictated the use of as much commercially available equipment as possible. The selected architecture uses a custom hardware interface to the existing RHIC BPM electronics together with commercially available Gigabit Ethernet switches to distribute position data to devices located around the collider ring. Using the minimum Ethernet packetmore » size and a field programmable gate array (FPGA) based state machine logic instead of a software based driver, real-time and deterministic data delivery is possible using Ethernet. The method of adapting this protocol for low latency data delivery, bench testing of Ethernet hardware, and the logic to construct Ethernet packets using FPGA hardware will be discussed. A robust communications system using almost all commercial off-the-shelf equipment was developed in under a year which enabled retrofitting of the existing RHIC BPM system to provide 10 KHz data delivery for a global orbit feedback scheme using 72 BPMs. Total latencies from data acquisition at the BPMs to delivery at the controller modules, including very long transmission distances, were kept under 100 {micro}s, which provide very little phase error in correcting the 10 Hz oscillations. Leveraging off of the speed of Gigabit Ethernet and wide availability of Ethernet products enabled this solution to be fully implemented in a much shorter time and at lower cost than if a similar network was developed using a proprietary method.« less

Bulk and dispersed aqueous behaviour of an endogenous lipid, selachyl alcohol: Effect of Tween 80 and Pluronic F127 on nanostructure.

PubMed

Younus, Mohammad; Hawley, Adrian; Boyd, Ben J; Rizwan, Shakila B

2018-05-07

Tween 80 has been reported to provide a means of targeting drug nanocarriers to the blood- brain barrier. This study investigated the influence of addition of Tween 80 on the formation of different bulk and dispersed lyotropic liquid crystalline phases in selachyl alcohol-based systems. The effect of increasing concentrations of Tween 80 and Pluronic F127 (as a control) (0-25% w/w relative to SA) on the bulk phase behaviour and dispersions of selachyl alcohol (SA) were investigated using small angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy. The addition of Tween 80 to SA bulk phase samples triggered concentration-dependent phase changes with the structure sequentially evolving from a reverse hexagonal phase (H 2 ) to a mixed H 2 and inverse bicontinuous cubic (V 2 ) then a V 2 phase alone. In contrast, the addition of Pluronic F127 resulted in a phase change from H 2 phase to a mixed lamellar and H 2 phase system. The mean particle size of internally structured particles was 125-190 nm with low polydispersity indices (0.1-0.2). Nanoparticles retained the bulk phase internal structure in the presence of Tween 80, whereas in the presence of Pluronic F127, the additional lamellar phase that formed in bulk phase systems was not observed. Cryo-TEM revealed the formation of cubosomes and hexosomes by SA in excess water in the presence of Tween 80 and Pluronic F127 respectively. In summary, it was shown that stabilisation of SA dispersions using Tween 80 resulted in a decrease in negative curvature leading to a change in internal structure from H 2 to V 2 phase. The studies provide the core understanding of particle structure to progress these structured lipid nanocarriers into delivery studies with Tween 80 as a mechanism to target the blood-brain barrier. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Qualification of a sublimation tool applied to the case of metalorganic chemical vapor deposition of In{sub 2}O{sub 3} from In(tmhd){sub 3} as a solid precursor

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

Szkutnik, P. D., E-mail: pierre.szkutnik@cea.fr; Jiménez, C.; Angélidès, L.

2016-02-15

A solid delivery system consisting of a source canister, a gas management, and temperature controlled enclosure designed and manufactured by Air Liquide Electronics Systems was tested in the context of gas-phase delivery of the In(tmhd){sub 3} solid precursor. The precursor stream was delivered to a thermal metalorganic chemical vapor deposition reactor to quantify deposition yield under various conditions of carrier gas flow and sublimation temperature. The data collected allowed the determination of characteristic parameters such as the maximum precursor flow rate (18.2 mg min{sup −1} in specified conditions) and the critical mass (defined as the minimum amount of precursor ablemore » to attain the maximum flow rate) found to be about 2.4 g, as well as an understanding of the influence of powder distribution inside the canister. Furthermore, this qualification enabled the determination of optimal delivery conditions which allowed for stable and reproducible precursor flow rates over long deposition times (equivalent to more than 47 h of experiment). The resulting In{sub 2}O{sub 3} layers was compared with those elaborated via pulsed liquid injection obtained in the same chemical vapor deposition chamber and under the same deposition conditions.« less

Solid lipid nanoparticles for the delivery of 1,3,5-triaza-7-phosphaadamantane (PTA) platinum (II) carboxylates.

PubMed

Sguizzato, Maddalena; Cortesi, Rita; Gallerani, Eleonora; Drechsler, Markus; Marvelli, Lorenza; Mariani, Paolo; Carducci, Federica; Gavioli, Riccardo; Esposito, Elisabetta; Bergamini, Paola

2017-05-01

The use of solid lipid nanoparticles (SLN) is a promising route for the delivery of platinum complexes aimed to anticancer activity. This paper describes the production and characterization of SLN suitable for the loading of Pt complexes containing the biocompatible phosphine 1,3,5-triaza-7-phosphaadamantane (PTA) as neutral ligand. After a screening of several lipidic phases, stearic acid-based SLN were identified as the most appropriate for the purpose. They were produced by emulsion-dilution method and then characterized in terms of dimension, polydispersity, time stability, pH balance and morphological aspect. Stearic acid SLN are designed as a system able to coordinate to platinum, acting as anionic carboxylic ligands, replacing the base carbonate of the Pt synthon [PtCO 3 (DMSO) 2 ], where also DMSO can subsequently be substituted by phosphinic ligands, namely PTA. SLN functionalised with Pt-PTA were produced and characterized by this synthetic route. The toxicity of plain SLN and the antiproliferative effect of SLN functionalised with Pt-PTA were evaluated on two human cancer cell lines K562 and A2780. The results indicate that SLN can be exploited as a delivery system for Pt complexes with potential anticancer activity. Copyright © 2016 Elsevier B.V. All rights reserved.

The use of solid supports to generate nucleic acid carriers.

PubMed

Unciti-Broceta, Asier; Díaz-Mochón, Juan José; Sánchez-Martín, Rosario M; Bradley, Mark

2012-07-17

Nucleic acids are the foundation stone of all cellular processes. Consequently, the use of DNA or RNA to treat genetic and acquired disorders (so called gene therapy) offers enormous potential benefits. The restitution of defective genes or the suppression of malignant genes could target a range of diseases, including cancers, inherited diseases (cystic fibrosis, muscular dystrophy, etc.), and viral infections. However, this strategy has a major barrier: the size and charge of nucleic acids largely restricts their transit into eukaryotic cells. Potential strategies to solve this problem include the use of a variety of natural and synthetic nucleic acid carriers. Driven by the aim and ambition of translating this promising therapeutic approach into the clinic, researchers have been actively developing advanced delivery systems for nucleic acids for more than 20 years. A decade ago we began our investigations of solid-phase techniques to construct families of novel nucleic acid carriers for transfection. We envisaged that the solid-phase synthesis of polycationic dendrimers and derivatized polyamimes would offer distinct advantages over solution phase techniques. Notably in solid phase synthesis we could take advantage of mass action and streamlined purification procedures, while simplifying the handling of compounds with high polarities and plurality of functional groups. Parallel synthesis methods would also allow rapid access to libraries of compounds with improved purities and yields over comparable solution methodologies and facilitate the development of structure activity relationships. We also twisted the concept of the solid-phase support on its head: we devised miniaturized solid supports that provided an innovative cell delivery vehicle in their own right, carrying covalently conjugated cargos (biomolecules) into cells. In this Account, we summarize the main outcomes of this series of chemically related projects.

Antibacterial Loaded Spray Dried Chitosan Polyelectrolyte Complexes as Dry Powder Aerosol for the Treatment of Lung Infections

PubMed Central

Mishra, Brahmeshwar; Mishra, Madhusmita; Yadav, Sarita Kumari

2017-01-01

Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections. Chitosan polyelectrolyte complex microparticles were formulated by spray drying process. Prepared spray dried chitosan PEC microparticles were studied for surface morphology, drug encapsulation efficiency, moisture content, Carr’s index, solid state interaction by XRD, aerosolization behaviour and in-vitro drug release. In-vitro cytotoxicity studies of microparticles were carried out on H1299 alveolar cell lines. Antibacterial efficacy of microparticles was assessed on the basis of determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of rats using PK/PD analysis. The PEC microparticles were mostly spherical and exhibited high drug encapsulation efficiency. Release profiles showed an initial burst phase followed by a secondary sustained release phase. Good aerosolization behaviour as dry powder inhaler was demonstrated by microparticles with high values of recovered dose, emitted dose, and fine particle fraction. No overt cytotoxicity of microparticles was detected against H1299 alveolar cell line. More than 8 to 9 folds higher Cmax values were obtained in BAL fluid with microparticles as compared to intravenously administered antibacterial solution. The findings of the study suggest that chitosan polyelectrolyte complex based microparticles as dry powder inhaler can be an efficient antibacterial delivery system for sustained and effective management of lung infection. PMID:28496463

Modified two-step emulsion solvent evaporation technique for fabricating biodegradable rod-shaped particles in the submicron size range.

PubMed

Safari, Hanieh; Adili, Reheman; Holinstat, Michael; Eniola-Adefeso, Omolola

2018-05-15

Though the emulsion solvent evaporation (ESE) technique has been previously modified to produce rod-shaped particles, it cannot generate small-sized rods for drug delivery applications due to the inherent coupling and contradicting requirements for the formation versus stretching of droplets. The separation of the droplet formation from the stretching step should enable the creation of submicron droplets that are then stretched in the second stage by manipulation of the system viscosity along with the surface-active molecule and oil-phase solvent. A two-step ESE protocol is evaluated where oil droplets are formed at low viscosity followed by a step increase in the aqueous phase viscosity to stretch droplets. Different surface-active molecules and oil phase solvents were evaluated to optimize the yield of biodegradable PLGA rods. Rods were assessed for drug loading via an imaging agent and vascular-targeted delivery application via blood flow adhesion assays. The two-step ESE method generated PLGA rods with major and minor axis down to 3.2 µm and 700 nm, respectively. Chloroform and sodium metaphosphate was the optimal solvent and surface-active molecule, respectively, for submicron rod fabrication. Rods demonstrated faster release of Nile Red compared to spheres and successfully targeted an inflamed endothelium under shear flow in vitro and in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

Frequency modulation system test procedure shuttle task 501 approach and landing test configuration

NASA Technical Reports Server (NTRS)

Doland, G. D.

1976-01-01

Shuttle Task 501 is an in-line task to test the performance and compatibility of radiofrequency links between the SSO and ground, and relay via a satellite. Under Shuttle Task 501 approach and landing test (ALT) phase only a limited portion of the communication and tracking (C&T) equipment is to be tested. The principal item to be tested is a frequency modulated (FM) data link. To test this RF link, an ALT FM System was designed, constructed, and the console wiring verified. A step-by-step procedure to be used to perform the ALT FM system is presented. The ALT FM system test is to be performed prior to delivery of the equipment to the Electronic Systems Test Laboratory (ESTL).

Concept for Sustained Plant Production on ISS Using VEGGIE Capillary Mat Rooting System

NASA Technical Reports Server (NTRS)

Stutte, Gary W.; Newsham, Gerard; Morrow, Robert M.; Wheeler, Raymond M.

2011-01-01

Plant growth in microgravity presents unique challenges associated with maintaining appropriate conditions for seed germination, seedling establishment, maturation and harvest. They include maintaining appropriate soil moisture content, nutrient balance, atmospheric mixing and containment. Sustained production imposes additional challenges of harvesting, replanting, and safety. The VEGGIE is a deployable (collapsible) plant growth chamber developed as part of a NASA SBIR Phase II by Orbitec, Madison, WI. The intent of VEGGIE is to provide a low-resource system to produce fresh vegetables for the crew on long duration missions. The VEGGIE uses and LED array for lighting, an expandable bellows for containment, and a capillary matting system for nutrient and water delivery. The project evaluated a number of approaches to achieve sustained production, and repeated plantings, using the capillary rooting system. A number of different root media, seed containment, and nutrient delivery systems were evaluated and effects on seed germination and growth were evaluated. A number of issues limiting sustained production, such as accumulation of nutrients, uniform water, elevated vapor pressure deficit, and media containment were identified. A concept using pre-planted rooting packs shown to effectively address a number of those issues and is a promising approach for future development as a planting system for microgravity conditions.

Diagnostic value of non stress test in latent phase of labor and maternal and fetal outcomes.

PubMed

Raouf, Shiva; Sheikhan, Fatemeh; Hassanpour, Shirin; Bani, Soheila; Torabi, Rogayye; Shamsalizadeh, Neda

2014-10-28

The Non Stress Test (NST) is the one of the significant diagnostic fetal well being testes. The purpose of this study is to access diagnostic value of NST during latent phase of labor by considering maternal and neonatal outcomes. This case study control study was performed on 450 healthy pregnant women with gestational age between 38-42 weeks in AL-Zahra teaching hospital in Tabriz, Iran. All participants underwent NST after being admitted to labor during their latent phase of delivery. Participants were divided into groups including the study group which included 150 participants with non-reactive NST results whereas 300 subjects with reactive NST results assigned in the control group. Subjects in both groups were hospitalized for pregnancy termination because of the delivery time. In order to find out the importance of routine performance of NST during delivery, the relationship between NST results and maternal and fetal outcomes was evaluated. Several criteria including type of delivery, meconium defecation, descent arrest, bradicardia, Apgar score, and still birth were compared between two types. Finding of this study showed that descent arrest occurred in 2.7% of the subjects in the study group, whereas it occurred in 4.7% of the participants in the control group (p=0.44). Bradicardia found in 28% of the participants in study group and 3.3% of the control group (p<0.001). The low Apgar Score was found in 2.7% of case group however; no the low apgar score detected in the control group. Meconium defecation observed in 11.3% of the subjects in the study group and 9.7% of the participants in control group (p=0.62). The amount of stillbirth were found in control group. There was a significant difference between the results of both groups in terms of bradicardia, descent arrest, and the low Apgar score and cesarean section. Results of this study revealed that participants in study group with nonreactive NST results had more fetal complications than those with reactive NST results. NST was found to be a value diagnostic test for diagnosis of fetal distress during delivery in the latent phase. This findings of this study suggest that NST should be performed routinely as a valuable diagnostic test during the latent phase of delivery.

Affordable Flight Demonstration of the GTX Air-Breathing SSTO Vehicle Concept

NASA Technical Reports Server (NTRS)

Krivanek, Thomas M.; Roche, Joseph M.; Riehl, John P.; Kosareo, Daniel N.

2002-01-01

The rocket based combined cycle (RBCC) powered single-stage-to-orbit (SSTO) reusable launch vehicle has the potential to significantly reduce the total cost per pound for orbital payload missions. To validate overall system performance, a flight demonstration must be performed. This paper presents an overview of the first phase of a flight demonstration program for the GTX SSTO vehicle concept. Phase 1 will validate the propulsion performance of the vehicle configuration over the supersonic and hypersonic airbreathing portions of the trajectory. The focus and goal of Phase 1 is to demonstrate the integration and performance of the propulsion system flowpath with the vehicle aerodynamics over the air-breathing trajectory. This demonstrator vehicle will have dual mode ramjet/scramjets, which include the inlet, combustor, and nozzle with geometrically scaled aerodynamic surface outer mold lines (OML) defining the forebody, boundary layer diverter, wings, and tail. The primary objective of this study is to demonstrate propulsion system performance and operability including the ram to scram transition, as well as to validate vehicle aerodynamics and propulsion airframe integration. To minimize overall risk and development cost the effort will incorporate proven materials, use existing turbomachinery in the propellant delivery systems, launch from an existing unmanned remote launch facility, and use basic vehicle recovery techniques to minimize control and landing requirements. A second phase would demonstrate propulsion performance across all critical portions of a space launch trajectory (lift off through transition to all-rocket) integrated with flight-like vehicle systems.

Affordable Flight Demonstration of the GTX Air-Breathing SSTO Vehicle Concept

NASA Technical Reports Server (NTRS)

Krivanek, Thomas M.; Roche, Joseph M.; Riehl, John P.; Kosareo, Daniel N.

2003-01-01

The rocket based combined cycle (RBCC) powered single-stage-to-orbit (SSTO) reusable launch vehicle has the potential to significantly reduce the total cost per pound for orbital payload missions. To validate overall system performance, a flight demonstration must be performed. This paper presents an overview of the first phase of a flight demonstration program for the GTX SSTO vehicle concept. Phase 1 will validate the propulsion performance of the vehicle configuration over the supersonic and hypersonic air- breathing portions of the trajectory. The focus and goal of Phase 1 is to demonstrate the integration and performance of the propulsion system flowpath with the vehicle aerodynamics over the air-breathing trajectory. This demonstrator vehicle will have dual mode ramjetkcramjets, which include the inlet, combustor, and nozzle with geometrically scaled aerodynamic surface outer mold lines (OML) defining the forebody, boundary layer diverter, wings, and tail. The primary objective of this study is to demon- strate propulsion system performance and operability including the ram to scram transition, as well as to validate vehicle aerodynamics and propulsion airframe integration. To minimize overall risk and develop ment cost the effort will incorporate proven materials, use existing turbomachinery in the propellant delivery systems, launch from an existing unmanned remote launch facility, and use basic vehicle recovery techniques to minimize control and landing requirements. A second phase would demonstrate propulsion performance across all critical portions of a space launch trajectory (lift off through transition to all-rocket) integrated with flight-like vehicle systems.

Metastable Radioxenon Verification Laboratory (MRVL) Year-End Report

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

Cooper, Matthew W.; Hayes, James C.; Lidey, Lance S.

2014-11-07

This is the year end report that is due to the client. The MRVL system is designed to measure multiple radioxenon isotopes ( 135Xe, 133Xe, 133mXe and 133mXe) simultaneously. The system has 12 channels to load samples and make nuclear measurements. Although the MRVL system has demonstrated excellent stability in measurements of Xe-133 and Xe-135 over the year of evaluation prior to delivery, there has been concern about system stability over measurements performed on samples with orders of magnitude different radioactivity, and samples containing multiple isotopes. To address these concerns, a series of evaluation test have been performed at themore » end-user laboratory. The evaluation was performed in two separate phases. Phase 1 made measurements on isotopically pure Xe-133 from high radioactivity down to the system background levels of activity, addressing the potential count rate dependencies when activities change from extreme high to very low. The second phase performed measurements on samples containing multiple isotopes (Xe-135, Xe-133 and Xe-133m), and addressed concerns about the dependence of isotopic concentrations on the presence of additional isotopes. The MRVL showed a concentration dependence on the Xe-133 due to the amount of Xe-133m that was in the sample. The dependency is due to the decay of Xe-133m into Xe-133. This document focuses on the second phase and will address the analysis used to account for ingrowth of Xe-133 from Xe-133m.« less

Enhanced Amendment Delivery to Subsurface Using Shear Thinning Fluid and Aqueous Foam for Metal, Radionuclide, and NAPL Remediation

NASA Astrophysics Data System (ADS)

Zhong, L.; Szecsody, J.; Li, X.; Oostrom, M.; Truex, M.

2010-12-01

In many contamination sites, removal of contaminants by any active remediation efforts is not practical due to the high cost and technological limitations. Alternatively, in situ remediation is expected to be the most important remediation strategy. Delivery of reactive amendment to the contamination zone is essential for the reactions between the contaminants and remedial amendments to proceed in situ. It is a challenge to effectively deliver remedial amendment to the subsurface contamination source areas in both aquifer and vadose zone. In aquifer, heterogeneity induces fluid bypassing the low-permeability zones, resulting in certain contaminated areas inaccessible to the remedial amendment delivered by water injection, thus inhibiting the success of remedial operations. In vadose zone in situ remediation, conventional solution injection and infiltration for amendment delivery have difficulties to achieve successful lateral spreading and uniform distribution of the reactive media. These approaches also tend to displace highly mobile metal and radionuclide contaminants such as hexavalent chromium [Cr(VI)] and technetium (Tc-99), causing spreading of contaminations. Shear thinning fluid and aqueous foam can be applied to enhance the amendment delivery and improve in situ subsurface remediation efficiency under aquifer and vadose zone conditions, respectively. Column and 2-D flow cell experiments were conducted to demonstrate the enhanced delivery and improved remediation achieved by the application of shear thinning fluid and foam injection at the laboratory scale. Solutions of biopolymer xanthan gum were used as the shear thinning delivering fluids. Surfactant sodium lauryl ether sulfate (STEOL CS-330) was the foaming agent. The shear thinning fluid delivery (STFD) considerably improved the sweeping efficiency over a heterogeneous system and enhanced the non-aqueous liquid phase (NAPL) removal. The delivery of amendment into low-perm zones (LPZs) by STFD also increased the persistence of amendment solution in the LPZs after injection. Immobilization of Tc-99 was improved when a reductant was delivered by foam versus by water-based solution to contaminated vadose zone sediments. Foam delivery remarkably improved the lateral distribution of fluids compared to direct liquid injection. In heterogeneous vadose zone formation, foam injection increased the liquid flow in the high permeable zones into which very limited fluid was distributed during liquid infiltration, demonstrating improved amendment distribution uniformity in the heterogeneous system by foam delivery.

Advanced Materials and Processing for Drug Delivery: The Past and the Future

PubMed Central

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

2012-01-01

Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. PMID:23088863

Two-dimensional parallel array technology as a new approach to automated combinatorial solid-phase organic synthesis

PubMed

Brennan; Biddison; Frauendorf; Schwarcz; Keen; Ecker; Davis; Tinder; Swayze

1998-01-01

An automated, 96-well parallel array synthesizer for solid-phase organic synthesis has been designed and constructed. The instrument employs a unique reagent array delivery format, in which each reagent utilized has a dedicated plumbing system. An inert atmosphere is maintained during all phases of a synthesis, and temperature can be controlled via a thermal transfer plate which holds the injection molded reaction block. The reaction plate assembly slides in the X-axis direction, while eight nozzle blocks holding the reagent lines slide in the Y-axis direction, allowing for the extremely rapid delivery of any of 64 reagents to 96 wells. In addition, there are six banks of fixed nozzle blocks, which deliver the same reagent or solvent to eight wells at once, for a total of 72 possible reagents. The instrument is controlled by software which allows the straightforward programming of the synthesis of a larger number of compounds. This is accomplished by supplying a general synthetic procedure in the form of a command file, which calls upon certain reagents to be added to specific wells via lookup in a sequence file. The bottle position, flow rate, and concentration of each reagent is stored in a separate reagent table file. To demonstrate the utility of the parallel array synthesizer, a small combinatorial library of hydroxamic acids was prepared in high throughput mode for biological screening. Approximately 1300 compounds were prepared on a 10 μmole scale (3-5 mg) in a few weeks. The resulting crude compounds were generally >80% pure, and were utilized directly for high throughput screening in antibacterial assays. Several active wells were found, and the activity was verified by solution-phase synthesis of analytically pure material, indicating that the system described herein is an efficient means for the parallel synthesis of compounds for lead discovery. Copyright 1998 John Wiley & Sons, Inc.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS.

PubMed

Gupta, Satish Kumar; Nutan

2013-10-22

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS

PubMed Central

Gupta, Satish Kumar; Nutan

2013-01-01

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward. PMID:24174883

Smart Nanoparticles Undergo Phase Transition for Enhanced Cellular Uptake and Subsequent Intracellular Drug Release in a Tumor Microenvironment.

PubMed

Ye, Guihua; Jiang, Yajun; Yang, Xiaoying; Hu, Hongxiang; Wang, Beibei; Sun, Lu; Yang, Victor C; Sun, Duxin; Gao, Wei

2018-01-10

Inefficient cellular uptake and intracellular drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. To overcome both problems, we designed a smart nanoparticle that undergoes phase transition in a tumor microenvironment (TME). The smart nanoparticle is generated using a lipid-polypetide hybrid nanoparticle, which comprises a PEGylated lipid monolayer shell and a pH-sensitive hydrophobic poly-l-histidine core and is loaded with the antitumor drug doxorubicin (DOX). The smart nanoparticle undergoes a two-step phase transition at two different pH values in the TME: (i) At the TME (pH e : 7.0-6.5), the smart nanoparticle swells, and its surface potential turns from negative to neutral, facilitating the cellular uptake; (ii) After internalization, at the acid endolysosome (pH endo : 6.5-4.5), the smart nanoparticle dissociates and induces endolysosome escape to release DOX into the cytoplasm. In addition, a tumor-penetrating peptide iNRG was modified on the surface of the smart nanoparticle as a tumor target moiety. The in vitro studies demonstrated that the iNGR-modified smart nanoparticles promoted cellular uptake in the acidic environment (pH 6.8). The in vivo studies showed that the iNGR-modified smart nanoparticles exerted more potent antitumor efficacy against late-stage aggressive breast carcinoma than free DOX. These data suggest that the smart nanoparticles may serve as a promising delivery system for sequential uptake and intracellular drug release of antitumor agents. The easy preparation of these smart nanoparticles may also have advantages in the future manufacture for clinical trials and clinical use.

Intra-arterial bromodeoxyuridine radiosensitization of malignant gliomas

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

Hegarty, T.J.; Thornton, A.F.; Diaz, R.F.

1990-08-01

In the 1950's it was first observed that mammalian cells exposed to the halogenated deoxyuridines were more sensitive to ultraviolet light and radiation than untreated cells. This prompted early clinical trials with bromodeoxyuridine (BUdR) which showed mixed results. More recently, several Phase I studies, while establishing the feasibility of continuous intravenous (IV) infusion of BUdR, have reported significant dose limiting skin and bone marrow toxicities and have questioned the optimal method of BUdR delivery. To exploit the high mitotic activity of malignant gliomas relative to surrounding normal brain tissue, we have developed a permanently implantable infusion pump system for safe,more » continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been treated in a Phase I clinical trial using IA BUdR (400-600 mg/m2/day X 8 1/2 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/2 weeks). Following initial biopsy/surgery the infusion pump system was implanted; BUdR infusion began 2 weeks prior to and continued throughout the 6 1/2 week course of radiotherapy. There have been no vascular complications. Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring dose reduction occurred in one patient. An overall Kaplan-Meier estimated median survival of 20 months has been achieved. As in larger controlled series, histologic grade and age are prognostically significant. We have shown in a Phase I study that IA BUdR radiosensitization is safe, tolerable, may lead to improved survival, and appears to be an efficacious primary treatment of malignant gliomas.« less

NIR‐Triggered Crystal Phase Transformation of NiTi‐Layered Double Hydroxides Films for Localized Chemothermal Tumor Therapy

PubMed Central

Wang, Donghui; Ge, Naijian; Yang, Tingting; Peng, Feng; Qiao, Yuqin; Li, Qianwen

2018-01-01

Abstract Construction of localized drug‐eluting systems with synergistic chemothermal tumor‐killing abilities is promising for biomedical implants directly contacting with tumor tissues. In this study, an intelligent and biocompatible drug‐loading platform, based on a gold nanorods‐modified butyrate‐inserted NiTi‐layered double hydroxides film (Au@LDH/B), is prepared on the surface of nitinol alloy. The prepared films function as drug‐loading “sponges,” which pump butyrate out under near‐infrared (NIR) irradiation and resorb drugs in water when the NIR laser is shut off. The stimuli‐responsive release of butyrate is verified to be related with the NIR‐triggered crystal phase transformation of Au@LDH/B. In vitro and in vivo studies reveal that the prepared films possess excellent biosafety and high efficiency in synergistic thermochemo tumor therapy, showing a promising application in the construction of localized stimuli‐responsive drug‐delivery systems. PMID:29721424

Kaiser Permanente-Sandia National Health Care Model: Phase 1 prototype final report. Part 2 -- Domain analysis

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

Edwards, D.; Yoshimura, A.; Butler, D.

This report describes the results of a Cooperative Research and Development Agreement between Sandia National Laboratories and Kaiser Permanente Southern California to develop a prototype computer model of Kaiser Permanente`s health care delivery system. As a discrete event simulation, SimHCO models for each of 100,000 patients the progression of disease, individual resource usage, and patient choices in a competitive environment. SimHCO is implemented in the object-oriented programming language C{sup 2}, stressing reusable knowledge and reusable software components. The versioned implementation of SimHCO showed that the object-oriented framework allows the program to grow in complexity in an incremental way. Furthermore, timingmore » calculations showed that SimHCO runs in a reasonable time on typical workstations, and that a second phase model will scale proportionally and run within the system constraints of contemporary computer technology.« less

Self-management toolkit and delivery strategy for end-of-life pain: the mixed-methods feasibility study.

PubMed

Bennett, Michael I; Mulvey, Matthew R; Campling, Natasha; Latter, Sue; Richardson, Alison; Bekker, Hilary; Blenkinsopp, Alison; Carder, Paul; Closs, Jose; Farrin, Amanda; Flemming, Kate; Gallagher, Jean; Meads, David; Morley, Stephen; O'Dwyer, John; Wright-Hughes, Alexandra; Hartley, Suzanne

2017-12-01

Pain affects most people approaching the end of life and can be severe for some. Opioid analgesia is effective, but evidence is needed about how best to support patients in managing these medicines. To develop a self-management support toolkit (SMST) and delivery strategy and to test the feasibility of evaluating this intervention in a future definitive trial. Phase I - evidence synthesis and qualitative interviews with patients and carers. Phase II - qualitative semistructured focus groups and interviews with patients, carers and specialist palliative care health professionals. Phase III - multicentre mixed-methods single-arm pre-post observational feasibility study. Phase I - six patients and carers. Phase II - 15 patients, four carers and 19 professionals. Phase III - 19 patients recruited to intervention that experienced pain, living at home and were treated with strong opioid analgesia. Process evaluation interviews with 13 patients, seven carers and 11 study nurses. Self-Management of Analgesia and Related Treatments at the end of life (SMART) intervention comprising a SMST and a four-step educational delivery approach by clinical nurse specialists in palliative care over 6 weeks. Recruitment rate, treatment fidelity, treatment acceptability, patient-reported outcomes (such as scores on the Brief Pain Inventory, Self-Efficacy for Managing Chronic Disease Scale, Edmonton Symptom Assessment Scale, EuroQol-5 Dimensions, Satisfaction with Information about Medicines Scale, and feasibility of collecting data on health-care resource use for economic evaluation). Phase I - key themes on supported self-management were identified from evidence synthesis and qualitative interviews. Phase II - the SMST was developed and refined. The delivery approach was nested within a nurse-patient consultation. Phase III - intervention was delivered to 17 (89%) patients, follow-up data at 6 weeks were available on 15 patients. Overall, the intervention was viewed as acceptable and valued. Descriptive analysis of patient-reported outcomes suggested that interference from pain and self-efficacy were likely to be candidates for primary outcomes in a future trial. No adverse events related to the intervention were reported. The health economic analysis suggested that SMART could be cost-effective. We identified key limitations and considerations for a future trial: improve recruitment through widening eligibility criteria, refine the SMST resources content, enhance fidelity of intervention delivery, secure research nurse support at recruiting sites, refine trial procedures (including withdrawal process and data collection frequency), and consider a cluster randomised design with nurse as cluster unit. (1) The recruitment rate was lower than anticipated. (2) The content of the intervention was focused on strong opioids only. (3) The fidelity of intervention delivery was limited by the need for ongoing training and support. (4) Recruitment sites where clinical research nurse support was not secured had lower recruitment rates. (5) The process for recording withdrawal was not sufficiently detailed. (6) The number of follow-up visits was considered burdensome for some participants. (7) The feasibility trial did not have a control arm or assess randomisation processes. A future randomised controlled trial is feasible and acceptable. This study is registered as PROSPERO CRD42014013572; Current Controlled Trials ISRCTN35327119; and National Institute for Health Research (NIHR) Portfolio registration 162114. The NIHR Health Technology Assessment programme.

A comparative assessment of cigarette smoke aerosols using an in vitro air–liquid interface cytotoxicity test

PubMed Central

Thorne, David; Dalrymple, Annette; Dillon, Deborah; Duke, Martin; Meredith, Clive

2015-01-01

Abstract This study describes the evaluation of a modified air-liquid interface BALB/c 3T3 cytotoxicity method for the assessment of smoke aerosols in vitro. The functionality and applicability of this modified protocol was assessed by comparing the cytotoxicity profiles from eight different cigarettes. Three reference cigarettes, 1R5F, 3R4F and CORESTA Monitor 7 were used to put the data into perspective and five bespoke experimental products were manufactured, ensuring a balanced and controlled study. Manufactured cigarettes were matched for key variables such as nicotine delivery, puff number, pressure drop, ventilation, carbon monoxide, nicotine free dry particulate matter and blend, but significantly modified for vapor phase delivery, via the addition of two different types and quantities of adsorptive carbon. Specifically manufacturing products ensures comparisons can be made in a consistent manner and allows the research to ask targeted questions, without confounding product variables. The results demonstrate vapor-phase associated cytotoxic effects and clear differences between the products tested and their cytotoxic profiles. This study has further characterized the in vitro vapor phase biological response relationship and confirmed that the biological response is directly proportional to the amount of available vapor phase toxicants in cigarette smoke, when using a Vitrocell® VC 10 exposure system. This study further supports and strengthens the use of aerosol based exposure options for the appropriate analysis of cigarette smoke induced responses in vitro and may be especially beneficial when comparing aerosols generated from alternative tobacco aerosol products. PMID:26339773

Free-Piston Stirling Power Conversion Unit for Fission Power System, Phase II Final Report

NASA Technical Reports Server (NTRS)

Wood, J. Gary; Stanley, John

2016-01-01

In Phase II, the manufacture and testing of two 6-kW(sub e)Stirling engines was completed. The engines were delivered in an opposed 12-kW(sub e) arrangement with a common expansion space heater head. As described in the Phase I report, the engines were designed to be sealed both hermetically and with a bolted O-ring seal. The completed Phase II convertor is in the bolted configuration to allow future disassembly. By the end of Phase II, the convertor had passed all of the final testing requirements in preparation for delivery to the NASA Glenn Research Center. The electronic controller also was fabricated and tested during Phase II. The controller sets both piston amplitudes and maintains the phasing between them. It also sets the operating frequency of the machine. Details of the controller are described in the Phase I final report. Fabrication of the direct-current to direct-current (DC-DC) output stage, which would have stepped down the main controller output voltage from 700 to 120 V(sub DC), was omitted from this phase of the project for budgetary reasons. However, the main controller was successfully built, tested with the engines, and delivered. We experienced very few development issues with this high-power controller. The project extended significantly longer than originally planned because of yearly funding delays. The team also experienced several hardware difficulties along the development path. Most of these were related to the different thermal expansions of adjacent parts constructed of different materials. This issue was made worse by the large size of the machine. Thermal expansion problems also caused difficulties in the brazing of the opposed stainless steel sodium-potassium (NaK) heater head. Despite repeated attempts Sunpower was not able to successfully braze the opposed head under this project. Near the end of the project, Glenn fabricated an opposed Inconel NaK head, which was installed prior to delivery for testing at Glenn. Engine development prior to this was performed using both single- and dual-opposed (common expansion space) Inconel heads with clamp-on electric heaters.

Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy

NASA Astrophysics Data System (ADS)

Kranz, Lena M.; Diken, Mustafa; Haas, Heinrich; Kreiter, Sebastian; Loquai, Carmen; Reuter, Kerstin C.; Meng, Martin; Fritz, Daniel; Vascotto, Fulvia; Hefesha, Hossam; Grunwitz, Christian; Vormehr, Mathias; Hüsemann, Yves; Selmi, Abderraouf; Kuhn, Andreas N.; Buck, Janina; Derhovanessian, Evelyna; Rae, Richard; Attig, Sebastian; Diekmann, Jan; Jabulowsky, Robert A.; Heesch, Sandra; Hassel, Jessica; Langguth, Peter; Grabbe, Stephan; Huber, Christoph; Türeci, Özlem; Sahin, Ugur

2016-06-01

Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.

SMART-1/CLEMENTINE Study of Humorum and Procellarum Basins

NASA Astrophysics Data System (ADS)

Carey, William; Foing, Bernard H.; Koschny, Detlef; Pio Rossi, Angelo; Josset, Jean-Luc

A study undertaken by ESA to define a European Reference Architecture for Space Exploration is due to be completed in September 2008. The development of this architecture over the past twelve months has identified a number of key capabilities, among them a lunar lander system, which could form the basis for Europe's contribution to the future exploration of space in collaboration with International Partners. The focus of this paper will be on the lunar lander system, and will present the results of an analysis of possible payloads that could be accommodated by the lander. As the industrial study is at the Phase 0 or Pre-Phase A level, the design of such a lander system is at a very early stage in its development, but an estimation of the payload capacity allows a general assessment of the types of possible payloads that could be carried, currently this capacity is estimated at 1.1 tonnes of gross payload mass to the lunar surface (assuming an Ariane 5 ECA launch). An important characteristic of the lunar lander is that it provides a versatile and flexible system for utilisation in a broad range of lunar missions which include: - Independent lunar exploration missions for science, technology demonstration and research. - Delivery of logistics and cargo to support human surface sortie missions. - Delivery of logistics to a lunar base/outpost. - Deployment of individual infrastructure elements in support of a lunar base/outpost. Based on the above different types of missions, a number of configurations of "reference payload" sets are in the process of being defined that cover specific exploration objectives related primarily to capability demonstration, exploration enabling research and enabled science. Aspects covered include: ISRU, robotics, mobility, human preparation, life science and geology. This paper will present the current status of definition of the Reference Payload sets.

Breath-powered sumatriptan dry nasal powder: an intranasal medication delivery system for acute treatment of migraine.

PubMed

Tepper, Stewart J; Johnstone, Merrilee R

2018-01-01

There is a need for fast-acting, non-oral medication options for migraine because some attacks develop rapidly and some are accompanied by nausea, vomiting, and gastroparesis, which can hinder oral medication uptake and absorption. The most commonly prescribed migraine medications are oral triptans, with sumatriptan as the most common. However, oral triptans are associated with adverse events (AEs) of atypical sensations that may be problematic for patients. Subcutaneous (SC) injectable sumatriptan and conventional liquid triptan nasal spray formulations are also available, but the frequency of atypical sensations is the highest with SC sumatriptan, and the intense bitter taste of conventional liquid triptan nasal spray discourages use. AVP-825 (ONZETRA ® Xsail ® ) is an intranasal medication delivery system containing 22 mg sumatriptan nasal powder that is now available in the USA for the acute treatment of migraine with or without aura in adults. The objective of this review is to summarize the development of AVP-825, which utilizes unique features of nasal anatomy to achieve efficient absorption and reduced systemic exposure. Literature searches for "sumatriptan nasal powder", "AVP-825", and "sumatriptan intranasal" were conducted. Review articles and pharmacokinetic, Phase II and Phase III studies were evaluated. AVP-825 demonstrates an earlier onset of efficacy and lower rate of atypical sensations than the oral standard of care, which can be attributed to its fast absorption and low systemic exposure. AEs of abnormal taste are predominantly mild. These results confirm the initial design concept for AVP-825, which aligned pharmacokinetics, anatomy, and drug presentation in a novel device to achieve optimal outcomes for the acute treatment of migraine.

Enhancement of C2C12 differentiation by perfluorocarbon-mediated oxygen delivery.

PubMed

Fujita, Hideaki; Shimizu, Kazunori; Morioka, Yuki; Nagamori, Eiji

2010-09-01

We have studied the effect of enhanced oxygen delivery by perfluorocarbons on the differentiation of C2C12 cells. The extent of differentiation was assessed by means of phase contrast/fluorescence microscopy, active tension measurement and the glucose consumption/lactate production rates. We found that enhanced oxygen delivery is suitable for full differentiation of C2C12 cells. Copyright 2010 The Society for Biotechnology, Japan. All rights reserved.

Applications of elastin-like polypeptides in drug delivery

PubMed Central

MacEwan, Sarah R; Chilkoti, Ashutosh

2014-01-01

Elastin-like polypeptides (ELPs) are biopolymers inspired by human elastin. Their lower critical solution temperature phase transition behavior and biocompatibility make them useful materials for stimulus-responsive applications in biological environments. Due to their genetically encoded design and recombinant synthesis, the sequence and size of ELPs can be exactly defined. These design parameters control the structure and function of the ELP with a precision that is unmatched by synthetic polymers. Due to these attributes, ELPs have been used extensively for drug delivery in a variety of different embodiments—as soluble macromolecular carriers, self-assembled nanoparticles, cross-linked microparticles, or thermally coacervated depots. These ELP systems have been used to deliver biologic therapeutics, radionuclides, and small molecule drugs to a variety of anatomical sites for the treatment of diseases including cancer, type 2 diabetes, osteoarthritis, and neuroinflammation. PMID:24979207

Management assessment of tank waste remediation system contractor readiness to proceed with phase 1B privatization

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

Honeyman, J.O.

1998-01-09

This Management Assessment of Tank Waste Remediation System (TWRS) Contractor Readiness to Proceed With Phase 1B Privatization documents the processes used to determine readiness to proceed with tank waste treatment technologies from private industry, now known as TWRS privatization. An overall systems approach was applied to develop action plans to support the retrieval and disposal mission of the TWRS Project. The systems and infrastructure required to support the mission are known. Required systems are either in place or plans have been developed to ensure they exist when needed. Since October 1996 a robust system engineering approach to establishing integrated Technicalmore » Baselines, work breakdown structures, tank farms organizational structure and configurations, work scope, and costs has become part of the culture within the TWRS Project. An analysis of the programmatic, management, and technical activities necessary to declare readiness to proceed with execution of the mission demonstrates that the system, personnel, and hardware will be on-line and ready to support the private contractors. The systems approach included defining the retrieval and disposal mission requirements and evaluating the readiness of the Project Hanford Management Contract (PHMC) team to support initiation of waste processing by the private contractors in June 2002 and to receive immobilized waste shortly thereafter. The Phase 1 feed delivery requirements from the private contractor Requests for Proposal were reviewed. Transfer piping routes were mapped, existing systems were evaluated, and upgrade requirements were defined.« less

Multifunctional Polymers and Composites for Self-Healing Applications

DTIC Science & Technology

2006-09-30

linkages (Chen et al. 2002), and a phase separated system based on polydimethylsiloxane (Cho et al. 2006). Self-healing occurs when monomer is released...WCI6 is shown in Figure 1.1a. The average particle sizes determined by analysis of SEM images for all three delivery methods are listed in Table 1.1...were then sieved and the beads smaller than 355 um were kept for further study. Elemental analysis of the wax beads revealed that the concentration of

Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries

DTIC Science & Technology

2017-08-01

INTRODUCTION Soldiers affected by eye injuries require immediate and effective treatment. The acute phase occurs at the time of the injury and results...C for 3min. The photoresist coated silicon wafer was exposed to 8 UV radiation through a mask containing a 3μm diameter circular pattern for 12s... Syndrome . Eur. J. Ophthalmol. 2013, 23, 368–376. 23. Acharya, G.; Shin, C. S.; McDermott, M.; Mishra, H.; Park, H.; Kwon, I. C.; Park, K. The Hydrogel

Proceedings of the Integrated Logistics Support Symposium held at Fort Worth, Texas on 30 November-2 December 1983.

DTIC Science & Technology

1983-12-02

load of the vehicles. The vehicles will be recycled several times to the shore to provide round-the-clock, sustained operations. Phase III...delivery and storage systems will be installed and operated. The containers and breakbulk cargo will be recycled to the respective ships to permit a total...encouraged to submit to the manager everything, inclut ing trivia , with the winnowing of what is reported upward left to the manager’s discretion

MOCVD Process Technology for Affordable, High-Yield, High-Performance MESFET Structures. MIMIC Phase 3

DTIC Science & Technology

1993-01-26

by an optical pyrometer that views the inside of the susceptor through a sapphire light pipe. The gas delivery system is of standard commercial design ...of the operating conditions for MESFET growth. 2.2.2 Modifications to the Apparatus for MIMIC Spire designed and installed a bell jar capable of...withstanding, without water cooling, the 500 to 1 100’C temperatures needed for MOCVD growth. The bell jar features a flow disrupter of proprietary design

The Effects of Intrapartum Supportive Care on Fear of Delivery and Labor Outcomes: A Single-Blind Randomized Controlled Trial.

PubMed

İsbir, Gözde Gökçe; Serçekuş, Pinar

2017-04-01

Supportive care during labor, the primary role of intrapartum nurses and midwives, provides comfort to prepartum women and helps facilitate a positive labor experience. It has been argued that supportive care during labor reduces fear and anxiety as well as the resultant side effects. However, evidence supporting this argument is insufficient. The aim of this study was to assess the effects of intrapartum supportive care on fear of delivery and on the key parameters of the labor process. This study used a single-blind randomized controlled trial approach. Randomized block assignment was used to assign 72 participants to either the intervention group (n = 36) or the control group (n = 36). Three women in the intervention group and six in the control group were later excluded from the study because they received emergency cesarean delivery. The intervention group received continuous supportive care, and the control group received routine hospital care. No significant differences were identified between the two groups at baseline. The intervention group reported less fear of delivery during the active and transient phases of labor, higher perceived support and control during delivery, lower pain scores during the transient phase of labor, and a shorter delivery period than the control group (p < .05). However, no significant difference in the use of oxytocin during delivery between the two groups was reported. The results of this evidence-based study suggest that continuous support during labor has clinically meaningful benefits for women and that all women should receive this support throughout their labor and delivery process.

Improvement of effect of water-in-oil microemulsion as an oral delivery system for fexofenadine: in vitro and in vivo studies

PubMed Central

Gundogdu, E; Alvarez, I Gonzalez; Karasulu, E

2011-01-01

Fexofenadine (FEX) has high solubility and low permeability (BCS, Class III). In this work, novel FEX loaded water in oil microemulsion (w/o) was designed to improve bioavailability and compared with Fexofen® syrup in in vitro and in vivo studies. In addition, pharmacokinetic parameters in permeability studies were estimated by using WinNonLin software program. w/o microemulsion system was optimized using a pseudoternary phase diagram, composed of span 80/lutrol F 68 (9.5:0.5 w/w), oleic acide, isopropyl alcohol and water as surfactant mixture; oil and cosurfactant was developed for oral drug delivery. w/o microemulsion systems were characterized by phase behavior, particle size, viscosity and solubilization capacity. In vitro studies were studied using Caco-2 cell monolayer. Pharmacokinetic parameters of w/o microemulsion were investigated in rabbits and compared to Fexofen® syrup. Fexofen® syrup and microemulsion were administered by oral gavage at 6 mg/kg of the same concentration. The experimental results indicated that microemulsion (HLB = 5.53) formed nanometer sized droplets (33.29 ± 1.76) and had good physical stability. This microemulsion increased the oral bioavailability of FEX which was highly water-soluble but fairly impermeable. The relative bioavailability of FEX microemulsion was about 376.76% compared with commercial syrup in rabbits. In vitro experiments were further employed for the enhanced effect of the microemulsion for FEX. These results suggest that novel w/o microemulsion plays an important role in enhancing oral bioavailability of low permeability drugs. PMID:21904453

An In-home Advanced Robotic System to Manage Elderly Home-care Patients' Medications: A Pilot Safety and Usability Study.

PubMed

Rantanen, Pekka; Parkkari, Timo; Leikola, Saija; Airaksinen, Marja; Lyles, Alan

2017-05-01

We examined the safety profile and usability of an integrated advanced robotic device and telecare system to promote medication adherence for elderly home-care patients. There were two phases. Phase I aimed to verify under controlled conditions in a single nursing home (n = 17 patients) that no robotic malfunctions would hinder the device's safe use. Phase II involved home-care patients from 3 sites (n = 27) who were on long-term medication. On-time dispensing and missed doses were recorded by the robotic system. Patients' and nurses' experiences were assessed with structured interviews. The 17 nursing home patients had 457 total days using the device (Phase I; mean, 26.9 per patient). On-time sachet retrieval occurred with 97.7% of the alerts, and no medication doses were missed. At baseline, Phase II home-dwelling patients reported difficulty remembering to take their medicines (23%), and 18% missed at least 2 doses per week. Most Phase II patients (78%) lived alone. The device delivered and patients retrieved medicine sachets for 99% of the alerts. All patients and 96% of nurses reported the device was easy to use. This trial demonstrated the safety profile and usability of an in-home advanced robotic device and telecare system and its acceptability to patients and nurses. It supports individualized patient dosing schedules, patient-provider communications, and on-time, in-home medication delivery to promote adherence. Real time dose-by-dose monitoring and communication with providers if a dose is missed provide oversight generally not seen in home care. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A novel needleless liquid jet injection methodology for improving direct cardiac gene delivery: An optimization of parameters, AAV mediated therapy and investigation of host responses in ischemic heart failure

NASA Astrophysics Data System (ADS)

Fargnoli, Anthony Samuel

Heart disease remains the leading cause of mortality and morbidity worldwide, with 22 million new patients diagnosed annually. Essentially, all present therapies have significant cost burden to the healthcare system, yet fail to increase survival rates. One key employed strategy is the genetic reprogramming of cells to increase contractility via gene therapy, which has advanced to Phase IIb Clinical Trials for advanced heart failure patients. It has been argued that the most significant barrier preventing FDA approval are resolving problems with safe, efficient myocardial delivery, whereby direct injection in the infarct and remote tissue areas is not clinically feasible. Here, we aim to: (1) Improve direct cardiac gene delivery through the development of a novel liquid jet device approach (2) Compare the new method against traditional IM injection with two different vector constructions and evaluate outcome (3) Evaluate the host response resulting from both modes of direct cardiac injection, then advance a drug/gene combination with controlled release nanoparticle formulations.

Formulation of Poloxamers for Drug Delivery

PubMed Central

Bodratti, Andrew M.; Alexandridis, Paschalis

2018-01-01

Poloxamers, also known as Pluronics®, are block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character and useful association and adsorption properties emanating from this. Poloxamers find use in many applications that require solubilization or stabilization of compounds and also have notable physiological properties, including low toxicity. Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current challenges facing nanomedicine revolve around the transport of typically water-insoluble drugs throughout the body, followed by targeted delivery. Judicious design of drug delivery systems leads to improved bioavailability, patient compliance and therapeutic outcomes. The rich phase behavior (micelles, hydrogels, lyotropic liquid crystals, etc.) of poloxamers makes them amenable to multiple types of processing and various product forms. In this review, we first present the general solution behavior of poloxamers, focusing on their self-assembly properties. This is followed by a discussion of how the self-assembly properties of poloxamers can be leveraged to encapsulate drugs using an array of processing techniques including direct solubilization, solvent displacement methods, emulsification and preparation of kinetically-frozen nanoparticles. Finally, we conclude with a summary and perspective. PMID:29346330

Continuing Professional Education Delivery Systems.

ERIC Educational Resources Information Center

Weeks, James P.

This investigation of delivery systems for continuing professional education provides an overview of current operational delivery systems in continuing professional education, drawing on experience as found in the literature. Learning theories and conclusions are woven into the descriptive text. Delivery systems profiled in the paper include the…

Apoptosis induction and anti-cancer activity of LeciPlex formulations.

PubMed

Dhawan, Vivek V; Joshi, Ganesh V; Jain, Ankitkumar S; Nikam, Yuvraj P; Gude, Rajiv P; Mulherkar, Rita; Nagarsenker, Mangal S

2014-10-01

Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery. Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential. In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system. Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.

Evolution in miniaturized column liquid chromatography instrumentation and applications: An overview.

PubMed

Nazario, Carlos E D; Silva, Meire R; Franco, Maraíssa S; Lanças, Fernando M

2015-11-20

The purpose of this article is to underline the miniaturized LC instrumental system and describe the evolution of commercially available systems by discussing their advantages and drawbacks. Nowadays, there are already many miniaturized LC systems available with a great variety of pump design, interface and detectors as well as efficient columns technologies and reduced connections devices. The solvent delivery systems are able to drive the mobile phase without flow splitters and promote gradient elution using either dual piston reciprocating or syringe-type pumps. The mass spectrometry as detection system is the most widely used detection system; among many alternative ionization sources direct-EI LC-MS is a promising alternative to APCI. In addition, capillary columns are now available showing many possibilities of stationary phases, inner diameters and hardware materials. This review provides a discussion about miniaturized LC demonstrating fundamentals and instrumentals' aspects of the commercially available miniaturized LC instrumental system mainly nano and micro LC formats. This review also covers the recent developments and trends in instrumentation, capillary and nano columns, and several applications of this very important and promising field. Copyright © 2015 Elsevier B.V. All rights reserved.

Microstructured bicontinuous phase formulations: their characterization and application in dermal and transdermal drug delivery.

PubMed

Lapteva, Maria; Kalia, Yogeshvar N

2013-08-01

The development of approaches to increase drug solubility and partitioning into the skin is an active area of research in topical and transdermal delivery. In addition to forming spherical aggregates, e.g., conventional oil in water or water in oil microemulsions, the combination of an oil, surfactant and water can create bicontinuous structures where the self-assembly properties of surfactants mean that the boundaries between oil and water are no longer random. This leads to the formation of specific microstructures whose intrinsic properties and interactions with the drug will determine the ability to formulate a given drug, its stability once formulated and its subsequent delivery. The review explores the relationship between the microstructure of biphasic formulations, present in microemulsions and liquid crystalline phases, and drug delivery into the skin. An overview of possible internal microstructures is followed by a summary of the methods used for structure characterization. The final section presents the work to-date and discusses the efficacy of such vehicles in enhancing dermal and transdermal delivery. The combination of water, surface agent and oil generates a broad range of three dimensional structures differing in both chemical and physical proprieties. Knowledge of the microstructure is important in understanding the behavior of a formulation and its effect on drug delivery into the skin. Microstructure complexity, interactions between the drug and the vehicle (i.e., location and mobility) and those between the vehicle and the skin are key determinants of drug delivery.

Phase Change Material Heat Sink for an ISS Flight Experiment

NASA Technical Reports Server (NTRS)

Quinn, Gregory; Stieber, Jesse; Sheth, Rubik; Ahlstrom, Thomas

2015-01-01

A flight experiment is being constructed to utilize the persistent microgravity environment of the International Space Station (ISS) to prove out operation of a microgravity compatible phase change material (PCM) heat sink. A PCM heat sink can help to reduce the overall mass and volume of future exploration spacecraft thermal control systems (TCS). The program is characterizing a new PCM heat sink that incorporates a novel phase management approach to prevent high pressures and structural deformation that often occur with PCM heat sinks undergoing cyclic operation in microgravity. The PCM unit was made using brazed aluminum construction with paraffin wax as the fusible material. It is designed to be installed into a propylene glycol and water cooling loop, with scaling consistent with the conceptual designs for the Orion Multipurpose Crew Vehicle. This paper reports on the construction of the PCM heat sink and on initial ground test results conducted at UTC Aerospace Systems prior to delivery to NASA. The prototype will be tested later on the ground and in orbit via a self-contained experiment package developed by NASA Johnson Space Center to operate in an ISS EXPRESS rack.

Hydrogen peroxide mechanosynthesis in siloxane-hydrogel contact lenses.

PubMed

Tavazzi, Silvia; Ferraro, Lorenzo; Cozza, Federica; Pastori, Valentina; Lecchi, Marzia; Farris, Stefano; Borghesi, Alessandro

2014-11-26

Drug-loaded contact lenses are emerging as the preferred treatment method for several ocular diseases, and efforts are being directed to promote extended and controlled delivery. One strategy is based on delivery induced by environmental triggers. One of these triggers can be hydrogen peroxide, since many platforms based on drug-loaded nanoparticles were demonstrated to be hydrogen-peroxide responsive. This is particularly interesting when hydrogen peroxide is the result of a specific pathophysiological condition. Otherwise, an alternative route to induce drug delivery is here proposed, namely the mechano-synthesis. The present work represents the proof-of-concept of the mechanosynthesis of hydrogen peroxide in siloxane-hydrogel contact lenses as a consequence of the cleavage of siloxane bonds at the interface between the polymer and water in aqueous phase. Their spongy morphology makes contact lenses promising systems for mechanical-to-chemical energy conversion, since the amount of hydrogen peroxide is expected to scale with the interfacial area between the polymer and water. The eyelid pressure during wear is sufficient to induce the hydrogen peroxide synthesis with concentrations which are biocompatible and suitable to trigger the drug release through hydrogen-peroxide-responsive platforms. For possible delivery on demand, the integration of piezoelectric polymers in the siloxane-hydrogel contact lenses could be designed, whose mechanical deformation could be induced by an applied wireless-controlled voltage.

Alternating-pulse iontophoresis for targeted cutaneous anesthesia

NASA Technical Reports Server (NTRS)

Meyer, Peter F.; Oddsson, Lars I E.

2003-01-01

In studies of sensory contributions to motor control, it may be advantageous to temporarily reduce the sensitivity of specific sensory systems. This article details a method for non-invasively inducing cutaneous anesthesia, leaving proprioceptive and motor functions intact. This method, called alternating-pulse iontophoresis, differs from conventional direct-current (DC) iontophoretic drug delivery in that adjacent drug delivery electrodes are stimulated out-of-phase. The total current delivered at any instant is then less than that produced during a comparable DC application, while the uniformity of drug delivery is expected to improve. Effective delivery of local anesthetics to the cutaneous foot soles by alternating-pulse iontophoresis was demonstrated using cutaneous pressure sensory threshold levels (STL's) assessed with Semmes-Weinstein monofilaments (arbitrary units of perceived force, or a.u.). Thirteen of 16 healthy subjects achieved a level of anesthesia greater than or equal to that normally associated with clinical peripheral sensory neuropathy. Average STL's measured prior to the anesthesia procedure were 4.00 a.u. ( approximately 10 mN). Immediately following the procedure, STL's were elevated to an average of 5.40 a.u. ( approximately 246 mN) and averaged 4.97 a.u. ( approximately 92 mN) after 50 min of standing. A number of research and clinical applications for this technique are suggested.

Space-based solar power conversion and delivery systems study. Volume 2: Engineering analysis

NASA Technical Reports Server (NTRS)

1977-01-01

The technical and economic feasibility of Satellite Solar Power Systems was studied with emphasis on the analysis and definition of an integrated strawman configuration concept, from which credible cost data could be estimated. Specifically, system concepts for each of the major subprogram areas were formulated, analyzed, and iterated to the degree necessary for establishing an overall, workable baseline system design. Cost data were estimated for the baseline and used to conduct economic analyses. The baseline concept selected was a 5-GW crystal silicon truss-type photovoltaic configuration, which represented the most mature concept available. The overall results and major findings, and the results of technical analyses performed during the final phase of the study efforts are reported.

High-intensity focused ultrasound (HIFU) array system for image-guided ablative therapy (IGAT)

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Keilman, George W.; Cunitz, Bryan W.; Martin, Roy W.; Vaezy, Shahram; Crum, Lawrence A.

2003-06-01

Recent interest in using High Intensity Focused Ultrasound (HIFU) for surgical applications such as hemostasis and tissue necrosis has stimulated the development of image-guided systems for non-invasive HIFU therapy. Seeking an all-ultrasound therapeutic modality, we have developed a clinical HIFU system comprising an integrated applicator that permits precisely registered HIFU therapy delivery and high quality ultrasound imaging using two separate arrays, a multi-channel signal generator and RF amplifier system, and a software program that provides the clinician with a graphical overlay of the ultrasound image and therapeutic protocol controls. Electronic phasing of a 32 element 2 MHz HIFU annular array allows adjusting the focus within the range of about 4 to 12 cm from the face. A central opening in the HIFU transducer permits mounting a commercial medical imaging scanhead (ATL P7-4) that is held in place within a special housing. This mechanical fixture ensures precise coaxial registration between the HIFU transducer and the image plane of the imaging probe. Recent enhancements include development of an acoustic lens using numerical simulations for use with a 5-element array. Our image-guided therapy system is very flexible and enables exploration of a variety of new HIFU therapy delivery and monitoring approaches in the search for safe, effective, and efficient treatment protocols.

In Situ Lipidization as a New Approach for the Design of a Self Microemulsifying Drug Delivery System (SMEDDS) of Doxorubicin Hydrochloride for Oral Administration.

PubMed

Derajram M Benival, M; Devarajan, Padma V

2015-05-01

The present paper reports in situ lipidization as a novel approach for the design of Dox-self microemulsifying drug delivery system (SMEDDS). Dox-aerosol OT (AOT) ion pair complex (lipidized Dox), exhibited high log P value of 1.74, indicating lipophilic nature. The lipidized Dox revealed good solubility but limited stability in various oils. Rapid complex formation of Dox with AOT dissolved in oils, and the high partitioning of lipidized Dox (-90%) into the oily phase presented in situ lipidization as a strategy to overcome the limited chemical stability of lipidized Dox. SMEDDS was prepared by mixing the lipidizing agent AOT, the surfactant α-Tocopheryl-Polyethyleneglycol-1 000-Succinate (TPGS) and Capmul as the oil. Dox was suspended in the SMEDDS to obtain Dox-SMEDDS. Dox-SMEDDS on aqueous dilution, resulted in a microemulsion with globule size 196 ± 16.56 nm, and revealed slow release of Dox. Oral bioavailability study in rats revealed a 420% enhancement from Dox-SMEDDS compared to Dox solution. Dox-SMEDDS and control group revealed comparable superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels in heart and kidneys suggesting safety of the Dox-SMEDDS. Efficacy study (tumor size reduction) in fibrosarcoma mouse model suggested Dox-SMEDDS as a promising oral delivery system for the treatment of cancer. In situ lipidization of Dox in SMEDDS presents a novel approach for the design of an orally bioavailable and promising formulation of Dox for oral administration.

TJC: plan and prepare for the transition to new tubing connectors to minimize the risk of dangerous misconnections, clinician frustration.

PubMed

2014-12-01

To reduce the risk of dangerous tubing misconnections, the ISO is rolling out new tubing connector standards that will eventually make it nearly impossible for tubing associated with one delivery system to be connected to a delivery system that serves a different purpose. Experts welcome the change, noting that tubing misconnections that cause injury and even death have been happening for years. However, TJC has issued a Sentinel Event Alert, warning that health care organizations need to be vigilant in managing the risk posed by these misconnections during the phased-in transition to the new connectors. Experts explain that tubing misconnections occur because many different types of tubing utilize the same Leur connector, making it possible for a clinician to mistakenly connect a tube to the wrong delivery system. The most common type of tubing misconnection reported to the ISMP is when a clinician wants to administer something to a patient through a feeding tube, but accidently administers the substance through an IV tube instead. The first new connector, called the ENFit, is going to be for enteral feeding tubes. It will not connect to IV tubing, making that type of misconnection unlikely. The new connector should be available early next year. Since hospitals will continue to use older tubing until their supplies are exhausted, manufacturers will temporarily provide adapters capable of making new administration sets compatible with older tubing.

Binary blend of glyceryl monooleate and glyceryl monostearate for magnetically induced thermo-responsive local drug delivery system.

PubMed

Mengesha, Abebe E; Wydra, Robert J; Hilt, J Zach; Bummer, Paul M

2013-12-01

To develop a novel monoglycerides-based thermal-sensitive drug delivery system, specifically for local intracavitary chemotherapy. Lipid matrices containing mixtures of glyceryl monooleate (GMO) and glyceryl monostearate (GMS) were evaluated for their potential application as magnetically induced thermo-responsive local drug delivery systems using a poorly water-soluble model drug, nifedipine (NF). Oleic acid-modified iron oxide (OA-Fe3O4) nanoparticles were embedded into the GMO-GMS matrix for remote activation of the drug release using an alternating magnetic field (AMF). The crystallization behavior of binary blends of GMO and GMS as characterized by DSC did show temperature dependent phase transition. GMO-GMS (75:25 wt%) blend showed a melting (T m ) and crystallization (T c ) points at 42°C and 37°C, respectively indicating the potential of the matrix to act as an 'on-demand' drug release. The matrix released only 35% of the loaded drug slowly in 10 days at 37°C whereas 96% release was obtained at 42°C. A concentration of 0.5% OA-Fe3O4 heated the matrix to 42.3 and 45.5°C within 5 min and 10 min of AMF exposure, respectively. The in vitro NF release profiles form the monoglycerides matrix containing 0.5% OA-Fe3O4 nanoparticles after AMF activation confirmed the thermo-responsive nature of the matrix that could provide pulsatile drug release 'on-demand'.

Comparative health systems research among Kaiser Permanente and other integrated delivery systems: a systematic literature review.

PubMed

Maeda, Jared Lane K; Lee, Karen M; Horberg, Michael

2014-01-01

Because of rising health care costs, wide variations in quality, and increased patient complexity, the US health care system is undergoing rapid changes that include payment reform and movement toward integrated delivery systems. Well-established integrated delivery systems, such as Kaiser Permanente (KP), should work to identify the specific system-level factors that result in superior patient outcomes in response to policymakers' concerns. Comparative health systems research can provide insights into which particular aspects of the integrated delivery system result in improved care delivery. To provide a baseline understanding of comparative health systems research related to integrated delivery systems and KP. Systematic literature review. We conducted a literature search on PubMed and the KP Publications Library. Studies that compared KP as a system or organization with other health care systems or across KP facilities internally were included. The literature search identified 1605 articles, of which 65 met the study inclusion criteria and were examined by 3 reviewers. Most comparative health systems studies focused on intra-KP comparisons (n = 42). Fewer studies compared KP with other US (n = 15) or international (n = 12) health care systems. Several themes emerged from the literature as possible factors that may contribute to improved care delivery in integrated delivery systems. Of all studies published by or about KP, only a small proportion of articles (4%) was identified as being comparative health systems research. Additional empirical studies that compare the specific factors of the integrated delivery system model with other systems of care are needed to better understand the "system-level" factors that result in improved and/or diminished care delivery.

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

DOT National Transportation Integrated Search

2012-05-16

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

77 FR 40693 - Bureau of Political-Military Affairs: Directorate of Defense Trade Controls; Notifications to the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

..., including technical data, and defense services for the design, development, manufacture, production... support the design, manufacturing and delivery phases of the SES-8 Commercial Communications Satellite... design, manufacture, test, on-ground launch-site delivery, completion of in-orbit testing and long-term...

Drug delivery systems with modified release for systemic and biophase bioavailability.

PubMed

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

Monolithic Integration of Two-Dimensional Liquid Chromatography-Capillary Electrophoresis and Electrospray Ionization on a Microfluidic Device

PubMed Central

Chambers, Andrew G.; Mellors, J. Scott; Henley, W. Hampton; Ramsey, J. Michael

2011-01-01

A microfluidic device capable of two-dimensional reversed-phase liquid chromatography-capillary electrophoresis with integrated electrospray ionization (LC-CE-ESI) for mass spectrometry (MS)-based proteomic applications is described. Traditional instrumentation was used for the LC sample injection and delivery of the LC mobile phase. The glass microfabricated device incorporated a sample-trapping region and an LC channel packed with reversed-phase particles. Rapid electrokinetic injections of the LC effluent into the CE dimension were performed at a cross channel intersection. The CE separation channel terminated at a corner of the square device, which functioned as an integrated electrospray tip. In addition to LC-CE-ESI, this device was used for LC-ESI without any instrumental modifications. To evaluate the system, LC-MS and LC-CE-MS analysis of protein digests were performed and compared. PMID:21214194

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

Schultz-Fellenz, Emily S.

A portion of LANL’s FY15 SPE objectives includes initial ground-based or ground-proximal investigations at the SPE Phase 2 site. The area of interest is the U2ez location in Yucca Flat. This collection serves as a baseline for discrimination of surface features and acquisition of topographic signatures prior to any development or pre-shot activities associated with SPE Phase 2. Our team originally intended to perform our field investigations using previously vetted ground-based (GB) LIDAR methodologies. However, the extended proposed time frame of the GB LIDAR data collection, and associated data processing time and delivery date, were unacceptable. After technical consultation andmore » careful literature research, LANL identified an alternative methodology to achieve our technical objectives and fully support critical model parameterization. Very-low-altitude unmanned aerial systems (UAS) photogrammetry appeared to satisfy our objectives in lieu of GB LIDAR. The SPE Phase 2 baseline collection was used as a test of this UAS photogrammetric methodology.« less

Evidence of an inverted hexagonal phase in self-assembled phospholipid-DNA-metal complexes

NASA Astrophysics Data System (ADS)

Francescangeli, O.; Pisani, M.; Stanic, V.; Bruni, P.; Weiss, T. M.

2004-08-01

We report the first observation of an inverted hexagonal phase of phospholipid-DNA-metal complexes. These ternary complexes are formed in a self-assembled manner when water solutions of neutral lipid dioleoylphosphatidylethanolamine (DOPE), DNA and divalent metal cations (Me2+; Me=Fe, Co, Mg, Mn) are mixed, which represents a striking example of supramolecular chemistry. The structure, derived from synchrotron X-ray diffraction, consists of cylindrical DNA strands coated by neutral lipid monolayers and arranged on a two-dimensional hexagonal lattice (HIIc). Besides the fundamental aspects, DOPE-DNA-Me2+ complexes may be of great interest as efficient nonviral delivery systems in gene therapy applications because of the low inherent cytotoxicity and the potential high transfection efficiency.

Dynamic simulation of motion effects in IMAT lung SBRT.

PubMed

Zou, Wei; Yin, Lingshu; Shen, Jiajian; Corradetti, Michael N; Kirk, Maura; Munbodh, Reshma; Fang, Penny; Jabbour, Salma K; Simone, Charles B; Yue, Ning J; Rengan, Ramesh; Teo, Boon-Keng Kevin

2014-11-01

Intensity modulated arc therapy (IMAT) has been widely adopted for Stereotactic Body Radiotherapy (SBRT) for lung cancer. While treatment dose is optimized and calculated on a static Computed Tomography (CT) image, the effect of the interplay between the target and linac multi-leaf collimator (MLC) motion is not well described and may result in deviations between delivered and planned dose. In this study, we investigated the dosimetric consequences of the inter-play effect on target and organs at risk (OAR) by simulating dynamic dose delivery using dynamic CT datasets. Fifteen stage I non-small cell lung cancer (NSCLC) patients with greater than 10 mm tumor motion treated with SBRT in 4 fractions to a dose of 50 Gy were retrospectively analyzed for this study. Each IMAT plan was initially optimized using two arcs. Simulated dynamic delivery was performed by associating the MLC leaf position, gantry angle and delivered beam monitor units (MUs) for each control point with different respiratory phases of the 4D-CT using machine delivery log files containing time stamps of the control points. Dose maps associated with each phase of the 4D-CT dose were calculated in the treatment planning system and accumulated using deformable image registration onto the exhale phase of the 4D-CT. The original IMAT plans were recalculated on the exhale phase of the CT for comparison with the dynamic simulation. The dose coverage of the PTV showed negligible variation between the static and dynamic simulation. There was less than 1.5% difference in PTV V95% and V90%. The average inter-fraction and cumulative dosimetric effects among all the patients were less than 0.5% for PTV V95% and V90% coverage and 0.8 Gy for the OARs. However, in patients where target is close to the organs, large variations were observed on great vessels and bronchus for as much as 4.9 Gy and 7.8 Gy. Limited variation in target dose coverage and OAR constraints were seen for each SBRT fraction as well as over all four fractions. Large dose variations were observed on critical organs in patients where these organs were closer to the target.

The impact of a preloaded intraocular lens delivery system on operating room efficiency in routine cataract surgery.

PubMed

Jones, Jason J; Chu, Jeffrey; Graham, Jacob; Zaluski, Serge; Rocha, Guillermo

2016-01-01

The aim of this study was to evaluate the operational impact of using preloaded intraocular lens (IOL) delivery systems compared with manually loaded IOL delivery processes during routine cataract surgeries. Time and motion data, staff and surgery schedules, and cost accounting reports were collected across three sites located in the US, France, and Canada. Time and motion data were collected for manually loaded IOL processes and preloaded IOL delivery systems over four surgery days. Staff and surgery schedules and cost accounting reports were collected during the 2 months prior and after introduction of the preloaded IOL delivery system. The study included a total of 154 routine cataract surgeries across all three sites. Of these, 77 surgeries were performed using a preloaded IOL delivery system, and the remaining 77 surgeries were performed using a manual IOL delivery process. Across all three sites, use of the preloaded IOL delivery system significantly decreased mean total case time by 6.2%-12.0% (P<0.001 for data from Canada and the US and P<0.05 for data from France). Use of the preloaded delivery system also decreased surgeon lens time, surgeon delays, and eliminated lens touches during IOL preparation. Compared to a manual IOL delivery process, use of a preloaded IOL delivery system for cataract surgery reduced total case time, total surgeon lens time, surgeon delays, and eliminated IOL touches. The time savings provided by the preloaded IOL delivery system provide an opportunity for sites to improve routine cataract surgery throughput without impacting surgeon or staff capacity.

Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle.

PubMed

Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue

2014-10-01

The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm(2)/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen.

Satellite Delivery of Aviation Weather Data

NASA Technical Reports Server (NTRS)

Kerczewski, Robert J.; Haendel, Richard

2001-01-01

With aviation traffic continuing to increase worldwide, reducing the aviation accident rate and aviation schedule delays is of critical importance. In the United States, the National Aeronautics and Space Administration (NASA) has established the Aviation Safety Program and the Aviation System Capacity Program to develop and test new technologies to increase aviation safety and system capacity. Weather is a significant contributor to aviation accidents and schedule delays. The timely dissemination of weather information to decision makers in the aviation system, particularly to pilots, is essential in reducing system delays and weather related aviation accidents. The NASA Glenn Research Center is investigating improved methods of weather information dissemination through satellite broadcasting directly to aircraft. This paper describes an on-going cooperative research program with NASA, Rockwell Collins, WorldSpace, Jeppesen and American Airlines to evaluate the use of satellite digital audio radio service (SDARS) for low cost broadcast of aviation weather information, called Satellite Weather Information Service (SWIS). The description and results of the completed SWIS Phase 1 are presented, and the description of the on-going SWIS Phase 2 is given.

High-resolution imaging of living mammalian cells bound by nanobeads-connected antibodies in a medium using scanning electron-assisted dielectric microscopy

NASA Astrophysics Data System (ADS)

Okada, Tomoko; Ogura, Toshihiko

2017-02-01

Nanometre-scale-resolution imaging technologies for liquid-phase specimens are indispensable tools in various scientific fields. In biology, observing untreated living cells in a medium is essential for analysing cellular functions. However, nanoparticles that bind living cells in a medium are hard to detect directly using traditional optical or electron microscopy. Therefore, we previously developed a novel scanning electron-assisted dielectric microscope (SE-ADM) capable of nanoscale observations. This method enables observation of intact cells in aqueous conditions. Here, we use this SE-ADM system to clearly observe antibody-binding nanobeads in liquid-phase. We also report the successful direct detection of streptavidin-conjugated nanobeads binding to untreated cells in a medium via a biotin-conjugated anti-CD44 antibody. Our system is capable of obtaining clear images of cellular organelles and beads on the cells at the same time. The direct observation of living cells with nanoparticles in a medium allowed by our system may contribute the development of carriers for drug delivery systems (DDS).

Erythrocytes-based synthetic delivery systems: transition from conventional to novel engineering strategies.

PubMed

Bhateria, Manisha; Rachumallu, Ramakrishna; Singh, Rajbir; Bhatta, Rabi Sankar

2014-08-01

Erythrocytes (red blood cells [RBCs]) and artificial or synthetic delivery systems such as liposomes, nanoparticles (NPs) are the most investigated carrier systems. Herein, progress made from conventional approach of using RBC as delivery systems to novel approach of using synthetic delivery systems based on RBC properties will be reviewed. We aim to highlight both conventional and novel approaches of using RBCs as potential carrier system. Conventional approaches which include two main strategies are: i) directly loading therapeutic moieties in RBCs; and ii) coupling them with RBCs whereas novel approaches exploit structural, mechanical and biological properties of RBCs to design synthetic delivery systems through various engineering strategies. Initial attempts included coupling of antibodies to liposomes to specifically target RBCs. Knowledge obtained from several studies led to the development of RBC membrane derived liposomes (nanoerythrosomes), inspiring future application of RBC or its structural features in other attractive delivery systems (hydrogels, filomicelles, microcapsules, micro- and NPs) for even greater potential. In conclusion, this review dwells upon comparative analysis of various conventional and novel engineering strategies in developing RBC based drug delivery systems, diversifying their applications in arena of drug delivery. Regardless of the challenges in front of us, RBC based delivery systems offer an exciting approach of exploiting biological entities in a multitude of medical applications.

Molecular Effects on Coacervate-Driven Block Copolymer Self Assembly

NASA Astrophysics Data System (ADS)

Lytle, Tyer; Radhakrishna, Mithun; Sing, Charles

Two oppositely charged polymers can undergo associative phase separation in a salt solution in a process known as \\x98complex coacervation. Recent work has used this as a motif to control the self-assembly behavior of a mixture of oppositely-charged block copolymers which form nanoscale structures. The materials formed from these complex coacervate-block copolymers (BCPs) have potential use as drug delivery systems, gels, and sensors. We have developed a hybrid Monte Carlo-Single Chain in a Mean Field (MC-SCMF) simulation method that is able to determine morphological phase diagrams for BCPs. This technique is an efficient way to calculate morphological phase diagrams and provides a clear link between molecular level features and self-assembly behaviors. Morphological phase diagrams showing the effects of polymer concentration, salt concentration, chain length, and charge-block fraction at large charge densities on self-assembly behavior have been determined. An unexpected phase transition from disorder to hexagonal packing at large salt concentrations has been observed for charge-block fractions equal to and larger than 0.5. This is attributed to the salt filling space stabilizing the morphology of the BCP.

Breeding behavior of northern saw-whet owls in Oregon

USGS Publications Warehouse

McCullough, Jenna M.; Conway, Courtney J.

2017-01-01

We know little about the breeding behavior of most nocturnal raptors. Nest attendance and prey delivery rates can be used as indices of relative habitat quality or extent of parental care. We used video cameras to document and observe prey delivery rates, nest attendance and bout durations at two northern saw-whet owl (Aegolius acadicus) nests in two artificial nest boxes in north-central Oregon. We collected 858 hours of video surveillance between 21 March and 01 June 2014. The number of prey deliveries per night increased as the nesting season progressed: 1.25 during laying, 1.33 during incubation, and 4.0 during the nestling phase. Prey was delivered most often between 2100 and 2200. Nest attendance by females was high during pre-laying (97.8%), laying (97.9%) and incubation (98.2%), but decreased during the nestling phase (55.7%). Nest attendance was higher during diurnal hours than nocturnal hours across all nesting phases. Duration of off bouts (recesses) was similar during pre-laying and laying (26 min), decreased during incubation (19 min), then increased during the nestling phase (55 min). One of the nesting attempts was successful and the female abandoned the other clutch 22 days after initiation. The incubation and nestling periods were 30 days each.

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

PubMed Central

Ko, Young Tag; Choi, Dong-Kug

2018-01-01

Solid lipid nanoparticle (SLN) delivery systems have a wide applicability in the delivery of phyto-bioactive compounds to treat various chronic diseases, including diabetes, cancer, obesity and neurodegenerative diseases. The multiple benefits of SLN delivery include improved stability, smaller particle size, leaching prevention and enhanced lymphatic uptake of the bioactive compounds through oral delivery. However, the burst release makes the SLN delivery systems inadequate for the oral delivery of various phyto-bioactive compounds that can treat such chronic diseases. Recently, the surface-modified SLN (SMSLN) was observed to overcome this limitation for oral delivery of phyto-bioactive compounds, and there is growing evidence of an enhanced uptake of curcumin delivered orally via SMSLNs in the brain. This review focuses on different SLN and SMSLN systems that are useful for oral delivery of phyto-bioactive compounds to treat various chronic diseases. PMID:29588585

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.

Biomaterials for drug delivery systems.

PubMed

Buckles, R G

1983-01-01

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

Manipulating the Ordered Nanostructure of Self-Assembled Monoolein and Phytantriol Nanoparticles with Unsaturated Fatty Acids.

PubMed

Tran, Nhiem; Mulet, Xavier; Hawley, Adrian M; Fong, Celesta; Zhai, Jiali; Le, Tu C; Ratcliffe, Julian; Drummond, Calum J

2018-02-27

Mesophase structures of self-assembled lyotropic liquid crystalline nanoparticles are important factors that directly influence their ability to encapsulate and release drugs and their biological activities. However, it is difficult to predict and precisely control the mesophase behavior of these materials, especially in complex systems with several components. In this study, we report the controlled manipulation of mesophase structures of monoolein (MO) and phytantriol (PHYT) nanoparticles by adding unsaturated fatty acids (FAs). By using high throughput formulation and small-angle X-ray scattering characterization methods, the effects of FAs chain length, cis-trans isomerism, double bond location, and level of chain unsaturation on self-assembled systems are determined. Additionally, the influence of temperature on the phase behavior of these nanoparticles is analyzed. We found that in general, the addition of unsaturated FAs to MO and PHYT induces the formation of mesophases with higher Gaussian surface curvatures. As a result, a rich variety of lipid polymorphs are found to correspond with the increasing amounts of FAs. These phases include inverse bicontinuous cubic, inverse hexagonal, and discrete micellar cubic phases and microemulsion. However, there are substantial differences between the phase behavior of nanoparticles with trans FA, cis FAs with one double bond, and cis FAs with multiple double bonds. Therefore, the material library produced in this study will assist the selection and development of nanoparticle-based drug delivery systems with desired mesophase.

Webcam delivery of the Camperdown Program for adolescents who stutter: a phase I trial.

PubMed

Carey, Brenda; O'Brian, Sue; Onslow, Mark; Packman, Ann; Menzies, Ross

2012-07-01

This Phase I clinical trial explored the viability of webcam Internet delivery of the Camperdown Program for adolescents who stutter. Method and Procedure Participants were 3 adolescents ages 13, 15, and 16 years, with moderate-severe stuttering. Each was treated with the Camperdown Program delivered by webcam with no clinic attendance. Primary outcome measures were percentage of syllables stuttered and number of treatment sessions to maintenance. Secondary outcome measures were speech naturalness, situation avoidance, self-reported stuttering severity, and parent and adolescent satisfaction. Data were collected pre treatment and at 1 day, 6 months, and 12 months post entry to maintenance. Participants entered maintenance after means of 18 sessions and 11 clinician hours. Group mean reduction of stuttering from pre treatment to entry to maintenance was 83%, from pre treatment to 6 months post entry to maintenance was 93%, and from pre treatment to 12 months post entry to maintenance was 74%. Self-reported stuttering severity ratings confirmed these results. Post entry to maintenance speech naturalness for participants fell within the range of that of 3 matched controls. However, avoidance of speech situations showed no corresponding improvements for 2 of the participants. The service delivery model was efficacious and efficient. All of the participants and their parents also found it appealing. Results justify a Phase II trial of the delivery model.

Probabilistic modeling of percutaneous absorption for risk-based exposure assessments and transdermal drug delivery.

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

Ho, Clifford Kuofei

Chemical transport through human skin can play a significant role in human exposure to toxic chemicals in the workplace, as well as to chemical/biological warfare agents in the battlefield. The viability of transdermal drug delivery also relies on chemical transport processes through the skin. Models of percutaneous absorption are needed for risk-based exposure assessments and drug-delivery analyses, but previous mechanistic models have been largely deterministic. A probabilistic, transient, three-phase model of percutaneous absorption of chemicals has been developed to assess the relative importance of uncertain parameters and processes that may be important to risk-based assessments. Penetration routes through the skinmore » that were modeled include the following: (1) intercellular diffusion through the multiphase stratum corneum; (2) aqueous-phase diffusion through sweat ducts; and (3) oil-phase diffusion through hair follicles. Uncertainty distributions were developed for the model parameters, and a Monte Carlo analysis was performed to simulate probability distributions of mass fluxes through each of the routes. Sensitivity analyses using stepwise linear regression were also performed to identify model parameters that were most important to the simulated mass fluxes at different times. This probabilistic analysis of percutaneous absorption (PAPA) method has been developed to improve risk-based exposure assessments and transdermal drug-delivery analyses, where parameters and processes can be highly uncertain.« less

Wavefront sensing and adaptive control in phased array of fiber collimators

NASA Astrophysics Data System (ADS)

Lachinova, Svetlana L.; Vorontsov, Mikhail A.

2011-03-01

A new wavefront control approach for mitigation of atmospheric turbulence-induced wavefront phase aberrations in coherent fiber-array-based laser beam projection systems is introduced and analyzed. This approach is based on integration of wavefront sensing capabilities directly into the fiber-array transmitter aperture. In the coherent fiber array considered, we assume that each fiber collimator (subaperture) of the array is capable of precompensation of local (onsubaperture) wavefront phase tip and tilt aberrations using controllable rapid displacement of the tip of the delivery fiber at the collimating lens focal plane. In the technique proposed, this tip and tilt phase aberration control is based on maximization of the optical power received through the same fiber collimator using the stochastic parallel gradient descent (SPGD) technique. The coordinates of the fiber tip after the local tip and tilt aberrations are mitigated correspond to the coordinates of the focal-spot centroid of the optical wave backscattered off the target. Similar to a conventional Shack-Hartmann wavefront sensor, phase function over the entire fiber-array aperture can then be retrieved using the coordinates obtained. The piston phases that are required for coherent combining (phase locking) of the outgoing beams at the target plane can be further calculated from the reconstructed wavefront phase. Results of analysis and numerical simulations are presented. Performance of adaptive precompensation of phase aberrations in this laser beam projection system type is compared for various system configurations characterized by the number of fiber collimators and atmospheric turbulence conditions. The wavefront control concept presented can be effectively applied for long-range laser beam projection scenarios for which the time delay related with the double-pass laser beam propagation to the target and back is compared or even exceeds the characteristic time of the atmospheric turbulence change - scenarios when conventional target-in-the-loop phase-locking techniques fail.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Use of volumetric-modulated arc therapy for treatment of Hodgkin lymphoma

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

Lee, Young K., E-mail: Young.Lee@rmh.nhs.uk; Bedford, James L.; Taj, Mary

To evaluate volumetric-modulated arc therapy (VMAT) for treatment of Hodgkin lymphoma (HL) in patients where conventional radiotherapy was not deliverable. A planning computed tomography (CT) scan was acquired for a twelve-year-old boy with Stage IIIB nodular sclerosing HL postchemotherapy with positive positron emission tomography scan. VMAT was used for Phase 1 (19.8 Gy in 11 fractions) and Phase 2 (10.8 Gy in 6 fractions) treatment plans. Single anticlockwise arc plans were constructed using SmartArc (Philips Radiation Oncology Systems, Fitchburg, WI) with control points spaced at 4°. The inverse-planning objectives were to uniformly irradiate the planning target volume (PTV) with themore » prescription dose while keeping the volume of lung receiving greater than 20 Gy (V{sub 20} {sub Gy}) to less than 30% and minimize the dose to the other adjacent organs at risk (OAR). Pretreatment verification was conducted and the treatment delivery was on an MLCi Synergy linear accelerator (Elekta Ltd, Crawley, UK). The planning results were retrospectively confirmed in a further 4 patients using a single PTV with a prescribed dose of 19.8 Gy in 11 fractions. Acceptable dose coverage and homogeneity were achieved for both Phase 1 and 2 plans while keeping the lung V{sub 20} {sub Gy} at 22.5% for the composite plan. The beam-on times for Phase 1 and Phase 2 plans were 109 and 200 seconds, respectively, and the total monitor units were 337.2 MU and 292.5 MU, respectively. The percentage of measured dose points within 3% and 3 mm for Phase 1 and Phase 2 were 92% and 98%, respectively. Both plans were delivered successfully. The retrospective planning study showed that VMAT improved PTV dose uniformity and reduced the irradiated volume of heart and lung, although the volume of lung irradiated to low doses increased. Two-phased VMAT offers an attractive option for large volume sites, such as HL, giving a high level of target coverage and significant OAR sparing together with efficient delivery.« less

A Path to Successful Energy Retrofits: Early Collaboration through Integrated Project Delivery Teams

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

Parrish, Kristen

2012-10-01

This document guides you through a process for the early design phases of retrofit projects to help you mitigate frustrations commonly experienced by building owners and designers. It outlines the value of forming an integrated project delivery team and developing a communication and information-sharing infrastructure that fosters collaboration. This guide does not present a complete process for designing an energy retrofit for a building. Instead, it focuses on the early design phase tasks related to developing and selecting energy efficiency measures (EEMs) that benefit from collaboration, and highlights the resulting advantages.

In vitro and in vivo topical delivery studies of tretinoin-loaded ultradeformable vesicles.

PubMed

Ascenso, Andreia; Salgado, Ana; Euletério, Carla; Praça, Fabíola Garcia; Bentley, Maria Vitória Lopes Badra; Marques, Helena C; Oliveira, Helena; Santos, Conceição; Simões, Sandra

2014-09-01

Ultradeformable vesicles are highly promising tools to enhance the percutaneous transport of different drugs such as tretinoin across the skin barrier and also to increase the formulation stability at absorption site and reduce the drug induced irritation. Topical delivery of tretinoin-loaded ultradeformable vesicles (tretinoin-UDV) was evaluated concerning different studies, such as: the release and permeation profiles (tape stripping); skin penetration (fluorescence analysis); induced electrical changes in skin barrier properties; cytotoxicity (Trypan Blue assay) and skin irritation in in vivo conditions (Draize test). The novel formulation performance was also compared to a commercial tretinoin formulation regarding in vivo studies. It was obtained a sustained and controlled drug release, as expected for UDV formulation. In addition, a dermal delivery was observed regarding the permeation study since it was not detected any drug amount in the receptor phase after 24h. Nile Red-UDV stained intensively mostly in the stratum corneum, corroborating the tape stripping results. Tretinoin-UDV decreased skin resistance, suggesting its ability to induce skin barrier disruption. Finally, the formulation vehicle (empty UDV) and tretinoin-UDV were not toxic under in vitro and in vivo conditions, at least, at 5×10(-3)mg/mL and 0.5mg/mL of tretinoin, respectively. Tretinoin-UDV is a promising delivery system for tretinoin dermal delivery without promoting skin irritation (unlike other commercial formulations), which is quite advantageous for therapeutic purpose. Copyright © 2014 Elsevier B.V. All rights reserved.

Multi-institutional application of Failure Mode and Effects Analysis (FMEA) to CyberKnife Stereotactic Body Radiation Therapy (SBRT).

PubMed

Veronese, Ivan; De Martin, Elena; Martinotti, Anna Stefania; Fumagalli, Maria Luisa; Vite, Cristina; Redaelli, Irene; Malatesta, Tiziana; Mancosu, Pietro; Beltramo, Giancarlo; Fariselli, Laura; Cantone, Marie Claire

2015-06-13

A multidisciplinary and multi-institutional working group applied the Failure Mode and Effects Analysis (FMEA) approach to assess the risks for patients undergoing Stereotactic Body Radiation Therapy (SBRT) treatments for lesions located in spine and liver in two CyberKnife® Centres. The various sub-processes characterizing the SBRT treatment were identified to generate the process trees of both the treatment planning and delivery phases. This analysis drove to the identification and subsequent scoring of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system. Novel solutions aimed to increase patient safety were accordingly considered. The process-tree characterising the SBRT treatment planning stage was composed with a total of 48 sub-processes. Similarly, 42 sub-processes were identified in the stage of delivery to liver tumours and 30 in the stage of delivery to spine lesions. All the sub-processes were judged to be potentially prone to one or more failure modes. Nineteen failures (i.e. 5 in treatment planning stage, 5 in the delivery to liver lesions and 9 in the delivery to spine lesions) were considered of high concern in view of the high RPN and/or severity index value. The analysis of the potential failures, their causes and effects allowed to improve the safety strategies already adopted in the clinical practice with additional measures for optimizing quality management workflow and increasing patient safety.

Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase

PubMed Central

Carroll, Marilyn E.; Kohl, Emily A.; Johnson, Krista M.; LaNasa, Rachel M.

2013-01-01

Background In previous studies with male and female rhesus monkeys withdrawal of access to oral phencyclidine (PCP) self administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer. Impulsive choice for SACC increased during PCP withdrawal more than females. Objectives The goal of the present study was to examine the effect of PCP (0.25 or 0.5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle. Materials and methods In Component 1 PCP and water were available from 2 drinking spouts for 1.5 h sessions under concurrent FR 16 schedules. In Component 2 a SACC solution was available for 45 min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6 ml) or 6 delayed SACC deliveries, and the delay was increased by 1 sec after a response on the delayed lever and decreased by 1 sec after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP-withdrawal, that occurred during the mid-folllicular phase (Days 7–11) or the late-luteal (Days 24–28) phase of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases. Results PCP deliveries were higher during the luteal vs the follicular phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration. Conclusions PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys. PMID:23344553

Rumen-stable delivery systems.

PubMed

Papas; Wu

1997-12-08

Ruminants have a distinct digestive system which serves a unique symbiotic relationship between the host animal and predominantly anaerobic rumen bacteria and protozoa. Rumen fermentation can be both beneficial by enabling utilization of cellulose and non-protein nitrogen and detrimental by reducing the nutritive value of some carbohydrates, high biological value proteins and by hydrogenating unsaturated lipids. In addition it can also result in the modification and inactivation of many pharmacologically active ingredients administered to the host animal via the oral route. The advances in ruminant nutrition and health demand a rumen-stable delivery system which can deliver the active ingredient post-ruminally while simultaneously meet efficacy, safety and cost criteria. In contrast to drug delivery systems for humans, the demand for low-cost has hindered the development of effective rumen-stable delivery systems. Historically, heat and chemical treatment of feed components, low solubility analogues or lipid-based formulations have been used to achieve some degree of rumen-stability, and products have been developed accordingly. Recently, a polymeric pH-dependent rumen-stable delivery system has been developed and commercialized. The rationale of this delivery system is based on the pH difference between ruminal and abomasal fluids. The delivery system is composed of a basic polymer, a hydrophobic substance and a pigment material. It can be applied as a coating to solid particles via a common encapsulation method such as air-suspension coating. In the future, the delivery system could be used to deliver micronutrients and pharmaceuticals post-ruminally to ruminant animals. A further possible application of the delivery system is that it could also be combined with other controlled delivery devices/systems in order to enhance slow release or to achieve targeted delivery needs for ruminants. This paper discusses the rumen protection and the abomasal release mechanism of the polymeric coating. It also reviews other rumen stable delivery systems and methods for evaluating their in vitro and in vivo performance.

Gel-like TPGS-Based Microemulsions for Imiquimod Dermal Delivery: Role of Mesostructure on the Uptake and Distribution into the Skin.

PubMed

Telò, Isabella; Favero, Elena Del; Cantù, Laura; Frattini, Noemi; Pescina, Silvia; Padula, Cristina; Santi, Patrizia; Sonvico, Fabio; Nicoli, Sara

2017-10-02

The aim of this work was to develop an innovative microemulsion with gel-like properties for the cutaneous delivery of imiquimod, an immunostimulant drug employed for the treatment of cutaneous infections and neoplastic conditions. A pseudoternary phase diagram was built using a 1/1 TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate)/Transcutol mixture as surfactant system, and oleic acid as oil phase. Eight microemulsions-selected from the 1.25/8.75 oil/surfactants ratio, along the water dilution line (from 20 to 56% w/w)-were characterized in terms of rheological behavior, optical properties via polarized microscopy, and supramolecular structure using X-ray scattering. Then, these formulations were loaded with imiquimod and the uptake and distribution into the skin was evaluated on full-thickness porcine skin. X-ray scattering experiments revealed the presence of disconnected drops in the case of microemulsion with 20% water content. Diluting the system up to 48% water content, the structure turned into an interconnected lamellar microemulsion, reaching a proper disconnected lamellar structure for the highest water percentages (52-56%). Upon water addition, also the rheological properties changed from nearly Newtonian fluids to gel-like structures, displaying the maximum of viscosity for the 48% water content. Skin uptake experiments demonstrated that formulation viscosity, drug loading, and surfactant concentration did not play an important role on imiquimod uptake into the skin, while the skin penetration was related instead to the microemulsion mesostructure. In fact, drug uptake became enhanced by locally lamellar interconnected structures, while it was reduced in the presence of disconnected structures, either drops or proper lamellae. Finally, the data demonstrated that mesostructure also affects the drug distribution between the epidermis and dermis. In particular, a significantly higher dermal accumulation was found when disconnected lamellar structures are present, suggesting the possibility of tuning both drug delivery and localization into the skin by modifying microemulsions composition.

Development of biodegradable drug delivery system to treat addiction.

PubMed

Mandal, T K

1999-06-01

Opiate addiction is a serious problem that has now spread worldwide to all levels of society. Buprenorphine has been used for several years for the treatment of opiate addiction. The objective of this project was to develop sustained-release biodegradable microcapsules for the parenteral delivery of buprenorphine. Biodegradable microcapsules of buprenorphine/poly(lactide-co-glycolide) were prepared using two main procedures based on an in-water drying process in a complex emulsion system. These procedures differ in the way the organic solvent was eliminated: evaporation or extraction. The effect of drug loading and the effect of partial saturation of the aqueous phase with the core material during the in-water solvent evaporation were also studied. The efficiency of encapsulation increased from 11% to 34% when the drug loading was decreased from 20% to 5%. There was no significant change in the efficiency of encapsulation when the aqueous phase was partially saturated with buprenorphine. In changing the solvent removal process from evaporation to extraction, no significant change in the efficiency of encapsulation was observed. The microcapsules prepared by the solvent evaporation were smooth and spherical. However, the microcapsules prepared by the extraction of the organic solvent lost their surface smoothness and became slightly irregular and porous compared with the other batches. The average particle size of the microcapsules was between 14 and 49 microns. The cumulative drug release was between 2% and 4% within the first 24 hr. A sustained drug release continued over 45 days.

Metabolic pathways and pharmacokinetics of natural medicines with low permeability.

PubMed

Zeng, Mei; Yang, Lan; He, Dan; Li, Yao; Shi, Mingxin; Zhang, Jingqing

2017-11-01

Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine. This review was performed using a systematic search of all available literature. It provides an overview and discussion of metabolic pathways and the pharmacokinetics of natural medicines with low permeability. The related enzymes and factors affecting them are analyzed. The series of metabolic reactions, including phase I reactions(oxidation hydrolysis, and reduction reactions) and phase II reactions (binding reactions), catalyzed by intracellular metabolic enzymes (such as CYP450, esterase, SULT, and UGT enzymes) in tissues (such as liver and gastro-intestinal tract) or in the body fluid environment were examined. The administration route, drug dose, and delivery system had a large influence on absorption, metabolism, and pharmacokinetics. Natural medicines with low permeability had distinctive metabolisms and pharmacokinetics. The metabolic and in vivo kinetic properties were favorably modified by choosing suitable drug delivery systems, administration routes and drug doses, among other variables. This study provides valuable information for clinicians and pharmacists to guide patients safe, effective, and rational drug use. The research of metabolism and pharmacokinetics is significant in guiding personalized clinical medicine.

Effect of Protein Incorporation on the Nanostructure of the Bicontinuous Microemulsion Phase of Winsor-III Systems: A Small-Angle Neutron Scattering Study

DOE PAGES

Hayes, Douglas G.; Gomez del Rio, Javier A.; Ye, Ran; ...

2015-01-20

Small-angle neutron scattering (SANS) analysis using the Teubner₋Strey model has been employed to evaluate the effect of protein incorporation into the middle, bicontinuous microemulsion (BμE) phase of Winsor-III (W III) systems formed by an aerosol-OT (AOT)/alkyl ethoxylate mixed surfactant system to understand better the extraction of proteins into and out of BμEs and to study the effect of proteins on a system that serves as a biomimetic analog of cell membranes. Under conditions of high salinity, the incorporation of positively charged proteins cytochrome c, lysozyme, and α-chymotrypsin, near their solubilization limit in the BμEs promoted the release of water andmore » oil from the BμEs, a decrease in the quasi-periodic repeat distance (d), an increase in ordering (a decrease in the amphiphilicity factor, f a) for the surfactant monolayers, and a decrease in the surface area per surfactant headgroup, suggesting that the proteins affected the self-assembly of components in the BμE phase and produced Debye shielding of AOTs sulfonate headgroup. For W III systems possessing lower salinity, cytochrome c reduced the efficiency of surfactant in the BμE phase, noted by increases in d and f a, suggesting that the enzyme and AOT underwent ion pairing. We find that the results of this study demonstrate the importance of ionic strength to modulate proteinsurfactant interactions, which in turn will control the release of proteins encapsulated in the BμEs, relevant to W III-based protein extraction and controlled release from BμE delivery systems, and demonstrate the utility of BμEs as a model system to understand the effect of proteins on biomembranes.« less

Lipid based nanoemulsifying resveratrol for improved physicochemical characteristics, in vitro cytotoxicity and in vivo antiangiogenic efficacy.

PubMed

Pund, Swati; Thakur, Rohit; More, Umesh; Joshi, Amita

2014-08-01

Resveratrol, a dietary non-flavonoid polyphenolic phytoalexin, has gained attention in cancer chemoprevention. However, poor aqueous solubility and cellular bioavailability has limited its therapeutic application. We formulated a lipid based delivery system of resveratrol with self nanoemulsifying ability. Several edible and safe lipids, surfactants and cosolvents were screened for solubilization of resevratrol. Developed formulation comprised of Acrysol K 150 as a lipid and mixture of Labrasol and Transcutol HP as the surfactant system, as these components showed higher solubility. Pseudoternary phase diagram was constructed to identify the region of nanoemulsification. The formulations showed rapid emulsification with an average globule diameter; 85nm to 120nm and slight negative zeta potential. The nanocompositions exhibited cloud point above 55°C and were stable toward the gastrointestinal pH and thermodynamic stress testing. As compared to pristine resveratrol, the developed delivery system showed significant increase in vitro cytotoxicity in MCF-7 breast cancer cells. In vivo chick chorioallantoic membrane assay revealed enhanced antiangiogenic activity of composition with high lipid level. Briefly, lipid based nanoemulsifying resveratrol dramatically enhanced the anticancer and antiangiogenic activities, thus increasing its potential application in cancer chemotherapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Design strategies and applications of circulating cell-mediated drug delivery systems.

PubMed

Su, Yixue; Xie, Zhiwei; Kim, Gloria B; Dong, Cheng; Yang, Jian

2015-01-01

Drug delivery systems, particularly nanomaterial-based drug delivery systems, possess a tremendous amount of potential to improve diagnostic and therapeutic effects of drugs. Controlled drug delivery targeted to a specific disease is designed to significantly improve the pharmaceutical effects of drugs and reduce their side effects. Unfortunately, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even with the development of numerous surface markers and targeting modalities. Thus, alternative drug and nanomedicine targeting approaches are desired. Circulating cells, such as erythrocytes, leukocytes, and stem cells, present innate disease sensing and homing properties. Hence, using living cells as drug delivery carriers has gained increasing interest in recent years. This review highlights the recent advances in the design of cell-mediated drug delivery systems and targeting mechanisms. The approaches of drug encapsulation/conjugation to cell-carriers, cell-mediated targeting mechanisms, and the methods of controlled drug release are elaborated here. Cell-based "live" targeting and delivery could be used to facilitate a more specific, robust, and smart payload distribution for the next-generation drug delivery systems.

Project Delivery System Mode Decision Based on Uncertain AHP and Fuzzy Sets

NASA Astrophysics Data System (ADS)

Kaishan, Liu; Huimin, Li

2017-12-01

The project delivery system mode determines the contract pricing type, project management mode and the risk allocation among all participants. Different project delivery system modes have different characteristics and applicable scope. For the owners, the selection of the delivery mode is the key point to decide whether the project can achieve the expected benefits, it relates to the success or failure of project construction. Under the precondition of comprehensively considering the influence factors of the delivery mode, the model of project delivery system mode decision was set up on the basis of uncertain AHP and fuzzy sets, which can well consider the uncertainty and fuzziness when conducting the index evaluation and weight confirmation, so as to rapidly and effectively identify the most suitable delivery mode according to project characteristics. The effectiveness of the model has been verified via the actual case analysis in order to provide reference for the construction project delivery system mode.

Galactosylated polyaspartamide copolymers for siRNA targeted delivery to hepatocellular carcinoma cells.

PubMed

Cavallaro, Gennara; Farra, Rossella; Craparo, Emanuela Fabiola; Sardo, Carla; Porsio, Barbara; Giammona, Gaetano; Perrone, Francesca; Grassi, Mario; Pozzato, Gabriele; Grassi, Gabriele; Dapas, Barbara

2017-06-20

The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-d,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gene product involved in HCC. The presence of GAL residues in the polyplexes allows the targeting of HCC cells that express the asialo-glycoprotein receptor (ASGP-R). In these cells, but not in ASGP-R non-expressing cells, PHEA-DETA-PEG-GAL/siE2F1 polyplexes induce the reduction of the mRNA and protein levels of E2F1 and of E2F1-regulated genes, all involved in the promotion of the G1/S phase transition. This results in a decrease of cell proliferation with a G1/G0 phase cells accumulation. Notably, removal of GAL residue almost completely abrogates the targeting capacity of the developed polyplexes. In conclusion, the generated polyplexes demonstrate the potential to effectively contributing to the development of novel anti-HCC therapeutic approaches via a siRNA-targeted delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and characterization of p1025-loaded bioadhesive liquid-crystalline system for the prevention of Streptococcus mutans biofilms.

PubMed

Calixto, Giovana Maria Fioramonti; Duque, Cristiane; Aida, Kelly Limi; Dos Santos, Vanessa Rodrigues; Massunari, Loiane; Chorilli, Marlus

2018-01-01

Formation of a dental biofilm by Streptococcus mutans can cause dental caries, and remains a costly health problem worldwide. Recently, there has been a growing interest in the use of peptidic drugs, such as peptide p1025, analogous to the fragments 1025-1044 of S. mutans cellular adhesin, responsible for the adhesion and formation of dental biofilm. However, peptides have physicochemical characteristics that may affect their biological action, limiting their clinical performance. Therefore, drug-delivery systems, such as a bioadhesive liquid-crystalline system (LCS), may be attractive strategies for peptide delivery. Potentiation of the action of LCS can be achieved with the use of bioadhesive polymers to prolong their residence on the teeth. In line with this, three formulations - polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, oleic acid, and Carbopol C974P in different combinations (F1C, F2C, and F3C) were developed to observe the influence of water in the LCS, with the aim of achieving in situ gelling in the oral environment. These formulations were assessed by polarized light microscopy, small-angle X-ray scattering, rheological analysis, and in vitro bioadhesion analysis. Then, p1025 and a control (chlorhexidine) were incorporated into the aqueous phase of the formulation (F + p1025 and F + chlorhexidine), to determine their antibiofilm effect and toxicity on epithelial cells. Polarized light microscopy and small-angle X-ray scattering showed that F1C and F2C were LCS, whereas F3C was a microemulsion. F1C and F2C showed pseudoplastic behavior and F3C Newtonian behavior. F1C showed the highest elastic and bioadhesive characteristics compared to other formulations. Antibiofilm effects were observed for F + p1025 when applied in the surface-bound salivary phase. The p1025-loaded nanostructured LCS presented limited cytotoxicity and effectively reduced S. mutans biofilm formation, and could be a promising p1025-delivery strategy to prevent the formation of S. mutans dental biofilm.

White Book on Physical and Rehabilitation Medicine (PRM) in Europe. Chapter 8. The PRM specialty in the healthcare system and society.

PubMed

2018-04-01

In the context of the White Book of Physical and Rehabilitation Medicine (PRM) in Europe, this paper deals with a global overview of the role of PRM in healthcare systems in Europe. Several documents and reports by WHO and the UN call for the worldwide strengthening of rehabilitation as a key health strategy of the 21st century. Therefore, further implementation of PRM in healthcare systems is crucial. Many aspects need to be considered when implementing PRM in a health system. Since PRM should be provided along the whole continuum of care, a specific phase model has been developed. Those phases depend on patients' functional needs as well as on temporal aspects of a health condition: it can be congenital or acquired, and the disorder can have an acute onset or a progressive or degenerative course. The following phases are described in the paper: habilitation, prehabilitation, PRM in acute settings, in post-acute and in long-term settings. Regular triage and reassessment to assign the patient to the appropriate level and setting of rehabilitation care is mandatory. Therefore, rehabilitation services should be stratified and organized in networks, in order to allow for the best possible care adapted to the individual's needs and goals, over the continuum of care. Providing correct PRM services requires good planning of service delivery, capacity building and resource allocation. The needed resources are human (with complex multi-professional teams), technical (diagnostic and therapeutic equipment, equipment for performing complementary diagnostic means, rehabilitation technology and assistive devices), and financial. Decisions on the allocation of the usually limited resources require a reasoned process and clear and fair criteria. Principles of clinical governance must be respected, and appropriate competencies are required. Disease prevention (primary, secondary and tertiary), health maintenance and support in chronic conditions as well as global health promotion are gaining growing importance in PRM. They include encouraging physical activity and promoting healthy behavior aiming at the maintenance of maximum function and avoiding complications in disabling or progressive conditions. This is discussed in the paper together with some ethical reflections on the choices PRM physicians continuously have to make during service delivery.

Approaches to Neural Tissue Engineering Using Scaffolds for Drug Delivery

PubMed Central

Willerth, Stephanie M.; Sakiyama-Elbert, Shelly E.

2007-01-01

This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented. PMID:17482308

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,…

Variation in Supersaturation and Phase Behavior of Ezetimibe Amorphous Solid Dispersions upon Dissolution in Different Biorelevant Media.

PubMed

Elkhabaz, Ahmed; Sarkar, Sreya; Dinh, Janny K; Simpson, Garth J; Taylor, Lynne S

2018-01-02

The delivery of poorly water-soluble drugs using amorphous solid dispersions (ASDs) has been widely acknowledged as a promising strategy for enhancing oral bioavailability. Upon dissolution, ASDs have accelerated dissolution rates and yield supersaturated solutions leading to higher apparent solubilities. Understanding the complex phase behavior of ASDs during dissolution is crucial for developing an effective formulation. Since the absorption of a lipophilic, high permeability drug is determined primarily by the intraluminal dissolution process and the final concentration achieved, there is a need for evaluation in biorelevant dissolution media that simulate both fasting and fed gastrointestinal states. In this study, using ezetimibe as a model drug, three different ASDs were prepared using poly(acrylic acid) (PAA), polyvinylpyrrolidone (PVP), and hydroxypropyl methylcellulose acetyl succinate (HPMC-AS). Dissolution of ASDs was carried out in sodium phosphate buffer, fed-state simulated intestinal fluid (FeSSIF), and Ensure Plus to evaluate the impact of different dissolution media on release profile, supersaturation, and phase behavior. The supersaturation level and crystallization kinetics varied among the dispersions and were found to be highly dependent on the medium employed. The presence of solubilizing additives in biorelevant media greatly affected the generation and stabilization of supersaturated solutions. Second harmonic generation microscopy was found to enable the detection of crystals in all media including the highly turbid Ensure Plus system. In conclusion, it is important to evaluate the impact of complex biorelevant media on the dissolution performance of ASDs to better design supersaturating formulations for oral delivery.

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

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.

Prototype system of secure VOD

NASA Astrophysics Data System (ADS)

Minemura, Harumi; Yamaguchi, Tomohisa

1997-12-01

Secure digital contents delivery systems are to realize copyright protection and charging mechanism, and aim at secure delivery service of digital contents. Encrypted contents delivery and history (log) management are means to accomplish this purpose. Our final target is to realize a video-on-demand (VOD) system that can prevent illegal usage of video data and manage user history data to achieve a secure video delivery system on the Internet or Intranet. By now, mainly targeting client-server systems connected with enterprise LAN, we have implemented and evaluated a prototype system based on the investigation into the delivery method of encrypted video contents.

Epigallocatechin Gallate-Loaded Gelatin-g-Poly(N-Isopropylacrylamide) as a New Ophthalmic Pharmaceutical Formulation for Topical Use in the Treatment of Dry Eye Syndrome.

PubMed

Luo, Li-Jyuan; Lai, Jui-Yang

2017-08-24

Given that biodegradable in situ gelling delivery systems may have potential applications in the design of ophthalmic pharmaceutical formulations, this study, for the first time, aims to develop gelatin-g-poly(N-isopropylacrylamide) (GN) carriers for topical epigallocatechin gallate (EGCG) administration in the treatment of dry eye disease (DED). By temperature triggered sol-gel phase transition of copolymers, EGCG-loaded GN was prepared at 32 °C and characterized by FTIR, NMR, and HPLC analyses. Results of WST-1 and live/dead assays showed that GN materials have good compatibility with corneal epithelial cells. Gradual biodegradation of delivery carriers allowed sustained release of EGCG without drug toxicity. Anti-inflammatory and antioxidant activity studies also indicated effective therapeutic drug levels at each time point within 3 days of release. In a rabbit dry eye model, corneal epithelial defects was ameliorated by treatment with single-dose administration of EGCG-containing GN. Furthermore, drug molecules released from carrier materials could prevent further tear evaporation and loss of mucin-secreting goblet cells in diseased animals. Our findings suggest that GN carrier is responsible for enhanced pharmacological efficacy of topically instilled EGCG, thereby demonstrating the benefits of using biodegradable in situ gelling delivery system to overcome the drawbacks of limited dry eye relief associated with eye drop dosage form.

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2011 CFR

2011-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2010 CFR

2010-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2013 CFR

2013-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2014 CFR

2014-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2012 CFR

2012-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

Effect of Charge Patterning on the Phase Behavior of Polymer Coacervates for Charge Driven Self Assembly

NASA Astrophysics Data System (ADS)

Radhakrishna, Mithun; Sing, Charles E.

Oppositely charged polymers can undergo associative liquid-liquid phase separation when mixed under suitable conditions of ionic strength, temperature and pH to form what are known as `polymeric complex coacervates'. Polymer coacervates find use in diverse array of applications like microencapsulation, drug delivery, membrane filtration and underwater adhesives. The similarity between complex coacervate environments and those in biological systems has also found relevance in areas of bio-mimicry. Our previous works have demonstrated how local charge correlations and molecular connectivity can drastically affect the phase behavior of coacervates. The precise location of charges along the chain therefore dramatically influences the local charge correlations, which consequently influences the phase behavior of coacervates. We investigate the effect of charge patterning along the polymer chain on the phase behavior of coacervates in the framework of the Restricted Primitive Model using Gibbs Ensemble Monte Carlo simulations. Our results show that charge patterning dramatically changes the phase behavior of polymer coacervates, which contrasts with the predictions of the classical Voorn-Overbeek theory. This provides the basis for designing new materials through charge driven self assembly by controlling the positioning of the charged monomers along the chain.

AmeriFlux US-ORv Olentangy River Wetland Research Park

DOE Data Explorer

Bohrer, Gil [The Ohio State University

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-ORv Olentangy River Wetland Research Park. Site Description - The ORWRP site is a 21-ha large-scale, long-term wetland campus facility that is owned by Ohio State University. It is designed to provide teaching, research, and service related to wetland and river science and ecological engineering. The site has been developed in several phases: Phase 1 (1992 - 1994) - Construction of two 2.5-acre deepwater marshes and a river water delivery system began, with pumps installed on the floodplain to bring water from the Olentangy River. In May 1994, one wetland was planted with marsh vegetation, while the other remained as an unplanted control; Phase 2 (1994 - 1999) - Development of a research and teaching infrastructure took place with the construction of boardwalks, a pavilion, and a compound. The creation of the 7-acre naturally flooded oxbow was also included; Phase 3 (2000 - 2003) - As a research building was created, three additional wetlands were created in the vicinity of the building, including a stormwater wetland that receives runoff from the roof of the building; Phase 4 - The current phase involves research access to the Olentangy River.

Patient costs during tuberculosis treatment in Bangladesh and Tanzania: the potential of shorter regimens.

PubMed

Gospodarevskaya, E; Tulloch, O; Bunga, C; Ferdous, S; Jonas, A; Islam, S; Rahman, M; Hussain, M A; Haque, M N; Egwaga, S; Gardiner, E; PrayGod, G; Islam, M A; Mann, G H; Wells, W A; Squire, S B

2014-07-01

To estimate the costs incurred by patients during the intensive and continuation phases of the current 6-month tuberculosis (TB) regimen in Bangladesh and Tanzania, and thus identify potential benefits to patients of a shorter, 4-month treatment regimen. The validated Stop TB patient cost questionnaire was adapted and used in interviews with 190 patients in the continuation phase of treatment with current regimens. In both countries, overall patient costs were lower during 2 months of the continuation phase (US$74 in Tanzania and US$56 in Bangladesh) than during the 2 months of the intensive phase of treatment (US$150 and US$111, respectively). However, continuation phase patient costs still represented 89% and 77% of the 2-month average national income in the respective countries. Direct travel costs in some settings were kept low by local delivery system features such as community treatment observation. Lost productivity and costs for supplementary foods remained significant. Although it is not a straightforward exercise to determine the exact magnitude of likely savings, a shorter regimen would reduce out-of-pocket expenses incurred by patients in the most recent 2 months of the continuation phase and allow an earlier return to productive activities.

Emerging potential of stimulus-responsive nanosized anticancer drug delivery systems for systemic applications.

PubMed

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Madeshwaran, Thiagarajan; Hiep, Tran Tuan; Kandasamy, Umadevi; Oh, Kyung Taek; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2018-02-01

The development of novel drug delivery systems based on well-defined polymer therapeutics has led to significant improvements in the treatment of multiple disorders. Advances in material chemistry, nanotechnology, and nanomedicine have revolutionized the practices of drug delivery. Stimulus-responsive material-based nanosized drug delivery systems have remarkable properties that allow them to circumvent biological barriers and achieve targeted intracellular drug delivery. Specifically, the development of novel nanocarrier-based therapeutics is the need of the hour in managing complex diseases. In this review, we have briefly described the fundamentals of drug targeting to diseased tissues, physiological barriers in the human body, and the mechanisms/modes of drug-loaded carrier systems. To that end, this review serves as a comprehensive overview of the recent developments in stimulus-responsive drug delivery systems, with focus on their potential applications and impact on the future of drug delivery.

Glycerosomes: Use of hydrogenated soy phosphatidylcholine mixture and its effect on vesicle features and diclofenac skin penetration.

PubMed

Manca, Maria Letizia; Cencetti, Claudia; Matricardi, Pietro; Castangia, Ines; Zaru, Marco; Sales, Octavio Diez; Nacher, Amparo; Valenti, Donatella; Maccioni, Anna Maria; Fadda, Anna Maria; Manconi, Maria

2016-09-10

In this work, diclofenac was encapsulated, as sodium salt, in glycerosomes containing 10, 20 or 30% of glycerol in the water phase with the aim to ameliorate its topical efficacy. Taking into account previous findings, glycerosome formulation was modified, in terms of economic suitability, using a cheap and commercially available mixture of hydrogenated soy phosphatidylcholine (P90H). P90H glycerosomes were spherical and multilamellar; photon correlation spectroscopy showed that obtained vesicles were ∼131nm, slightly larger and more polydispersed than those made with dipalmitoylphosphatidylcholine (DPPC) but, surprisingly, they were able to ameliorate the local delivery of diclofenac, which was improved with respect to previous findings, in particular using glycerosomes containing high amount of glycerol (20 and 30%). Finally, this drug delivery system showed a high in vitro biocompatibility toward human keratinocytes. Copyright © 2016 Elsevier B.V. All rights reserved.

Doubling transmission capacity in optical wireless system by antenna horizontal- and vertical-polarization multiplexing.

PubMed

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

2013-06-15

We experimentally demonstrate 2×56 Gb/s two-channel polarization-division-multiplexing quadrature-phase-shift-keying signal delivery over 80 km single-mode fiber-28 and 2 m Q-band (33-50 GHz) wireless link, adopting antenna horizontal- (H-) and vertical-polarization (V-polarization) multiplexing. At the wireless receiver, classic constant-modulus-algorithm equalization based on digital signal processing can realize polarization demultiplexing and remove the crosstalk at the same antenna polarization. By adopting antenna polarization multiplexing, the signal baud rate and performance requirements for optical and wireless devices can be reduced but at the cost of double antennas and devices, while wireless transmission capacity can also be increased but at the cost of stricter requirements for V-polarization. The isolation is only about 19 dB when V-polarization deviation approaches 10°, which will affect high-speed (>50 Gb/s) wireless delivery.

An Overview of Insulin Pumps and Glucose Sensors for the Generalist

PubMed Central

McAdams, Brooke H.; Rizvi, Ali A.

2016-01-01

Continuous subcutaneous insulin, or the insulin pump, has gained popularity and sophistication as a near-physiologic programmable method of insulin delivery that is flexible and lifestyle-friendly. The introduction of continuous monitoring with glucose sensors provides unprecedented access to, and prediction of, a patient’s blood glucose levels. Efforts are underway to integrate the two technologies, from “sensor-augmented” and “sensor-driven” pumps to a fully-automated and independent sensing-and-delivery system. Implantable pumps and an early-phase “bionic pancreas” are also in active development. Fine-tuned “pancreas replacement” promises to be one of the many avenues that offers hope for individuals suffering from diabetes. Although endocrinologists and diabetes specialists will continue to maintain expertise in this field, it behooves the primary care physician to have a working knowledge of insulin pumps and sensors to ensure optimal clinical care and decision-making for their patients. PMID:26742082

The system with zwitterionic lactose-based surfactant for complexation and delivery of small interfering ribonucleic acid—A structural and spectroscopic study

NASA Astrophysics Data System (ADS)

Skupin, Michalina; Sobczak, Krzysztof; Zieliński, Ryszard; Kozak, Maciej

2016-05-01

Systems suitable for the effective preparation of complexes with siRNA (small interfering RNA) are at the center of interest in the area of research work on the delivery of the RNA-based drugs (RNA-therapeutics). This article presents results of a study on the structural effects associated with siRNA complexation by a surfactant comprising a lactose group (N-(3-propanesulfone)-N-dodecyl-amino-beta-D-lactose hydrochloride, LA12). The double stranded siRNA oligomer (21 base pairs) used in this study is responsible for silencing a gene that can be important in the therapy of myotonic dystrophy type 1. The obtained siRNA/LA12 lipoplexes were studied using the methods of small angle scattering of synchrotron radiation, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and electrophoretic mobility tests. Lipoplexes form in solution stable lamellar or cubic phases. The surfactant selected for the study shows much lower cytotoxicity and good complexation abilities of siRNA than dicationic or polycationic surfactants.

Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine.

PubMed

Cui, Shu-Xia; Nie, Shu-Fang; Li, Li; Wang, Chang-Guang; Pan, Wei-San; Sun, Jian-Ping

2009-05-01

The main purpose of current investigation is to prepare a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of vinpocetine, a poorly water-soluble drug. Suitable vehicles were screened by determining the solubility of vinpocetine in them. Certain surfactants were selected according to their emulsifying ability with different oils. Ternary phase diagrams were used to identify the efficient self-microemulsifying region and to screen the effect of surfactant/cosurfactant ratio (K(m)). The optimized formulation for in vitro dissolution and bioavailability assessment was oil (ethyl oleate, 15%), surfactant (Solutol HS 15, 50%), and cosurfactant (Transcutol P, 35%). The release rate of vinpocetine from SMEDDS was significantly higher than that of the commercial tablet. Pharmacokinetics and bioavailability of SMEDDS were evaluated. It was found that the oral bioavailability of vinpocetine of SMEDDS was 1.72-fold higher as compared with that of the commercial tablet. These results obtained demonstrated that vinpocetine absorption was enhanced significantly by employing SMEDDS. Therefore, SMEDDS might provide an efficient way of improving oral bioavailability of poorly water-soluble drugs.

The system with zwitterionic lactose-based surfactant for complexation and delivery of small interfering ribonucleic acid—A structural and spectroscopic study

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

Skupin, Michalina; Sobczak, Krzysztof; Zieliński, Ryszard

Systems suitable for the effective preparation of complexes with siRNA (small interfering RNA) are at the center of interest in the area of research work on the delivery of the RNA-based drugs (RNA-therapeutics). This article presents results of a study on the structural effects associated with siRNA complexation by a surfactant comprising a lactose group (N-(3-propanesulfone)-N-dodecyl-amino-beta-D-lactose hydrochloride, LA12). The double stranded siRNA oligomer (21 base pairs) used in this study is responsible for silencing a gene that can be important in the therapy of myotonic dystrophy type 1. The obtained siRNA/LA12 lipoplexes were studied using the methods of small anglemore » scattering of synchrotron radiation, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and electrophoretic mobility tests. Lipoplexes form in solution stable lamellar or cubic phases. The surfactant selected for the study shows much lower cytotoxicity and good complexation abilities of siRNA than dicationic or polycationic surfactants.« less

Development and optimisation of atorvastatin calcium loaded self-nanoemulsifying drug delivery system (SNEDDS) for enhancing oral bioavailability: in vitro and in vivo evaluation.

PubMed

Kassem, Abdulsalam M; Ibrahim, Hany M; Samy, Ahmed M

2017-05-01

The objective of this study was to develop and optimise self-nanoemulsifying drug delivery system (SNEDDS) of atorvastatin calcium (ATC) for improving dissolution rate and eventually oral bioavailability. Ternary phase diagrams were constructed on basis of solubility and emulsification studies. The composition of ATC-SNEDDS was optimised using the Box-Behnken optimisation design. Optimised ATC-SNEDDS was characterised for various physicochemical properties. Pharmacokinetic, pharmacodynamic and histological findings were performed in rats. Optimised ATC-SNEDDS resulted in droplets size of 5.66 nm, zeta potential of -19.52 mV, t 90 of 5.43 min and completely released ATC within 30 min irrespective of pH of the medium. Area under the curve of optimised ATC-SNEDDS in rats was 2.34-folds higher than ATC suspension. Pharmacodynamic studies revealed significant reduction in serum lipids of rats with fatty liver. Photomicrographs showed improvement in hepatocytes structure. In this study, we confirmed that ATC-SNEDDS would be a promising approach for improving oral bioavailability of ATC.

Design and evaluation of self-emulsifying drug delivery systems of Rhizoma corydalis decumbentis extracts.

PubMed

Ma, Hongda; Zhao, Qingchun; Wang, Yongjun; Guo, Tao; An, Ye; Shi, Guobing

2012-10-01

To improve the dissolution and oral absorption of Rhizoma corydalis decumbentis extracts (RCDE), a famous traditional Chinese herbal medicine which contains poorly water-soluble active components, self-emulsifying drug-delivery systems (SEDDS) were designed and evaluated in vitro and in vivo for the first time. Six formulations were prepared, and pseudoternary phase diagrams were constructed to identify the efficient self-emulsication region through the modified visual test. The optimized formulation consisted of 45% Solutol, 40% ethyl oleate, and 15% Transcutol P. The mean droplet size distribution of the optimized SEDDS was less than 100 nm. The release of the active components (protopine and tetrahydropalmatine) in RCDE from SEDDS hard gelatin capsules showed a faster rate in comparison with the commercial tablets. After oral administration of RCDE SEDDS capsules or the commercial tablets to fasted rats, the relative bioavailability of SEDDS capsules for protopine and tetrahydropalmatine was 209.7% and 133.2% compared with commercial tablets, respectively. Our study indicated that SEDDS has the potential to improve the bioavailability of traditional Chinese medicines, in which many active components are hydrophobic, such as RCDE.

Interaction of cholesterol-conjugated ionizable amino lipids with biomembranes: lipid polymorphism, structure-activity relationship, and implications for siRNA delivery.

PubMed

Zhang, Jingtao; Fan, Haihong; Levorse, Dorothy A; Crocker, Louis S

2011-08-02

Delivery of siRNA is a major obstacle to the advancement of RNAi as a novel therapeutic modality. Lipid nanoparticles (LNP) consisting of ionizable amino lipids are being developed as an important delivery platform for siRNAs, and significant efforts are being made to understand the structure-activity relationship (SAR) of the lipids. This article uses a combination of small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) to evaluate the interaction between cholesterol-conjugated ionizable amino lipids and biomembranes, focusing on an important area of lipid SAR--the ability of lipids to destabilize membrane bilayer structures and facilitate endosomal escape. In this study, cholesterol-conjugated amino lipids were found to be effective in increasing the order of biomembranes and also highly effective in inducing phase changes in biological membranes in vitro (i.e., the lamellar to inverted hexagonal phase transition). The phase transition temperatures, determined using SAXS and DSC, serve as an indicator for ranking the potency of lipids to destabilize endosomal membranes. It was found that the bilayer disruption ability of amino lipids depends strongly on the amino lipid concentration in membranes. Amino lipids with systematic variations in headgroups, the extent of ionization, tail length, the degree of unsaturation, and tail asymmetry were evaluated for their bilayer disruption ability to establish SAR. Overall, it was found that the impact of these lipid structure changes on their bilayer disruption ability agrees well with the results from a conceptual molecular "shape" analysis. Implications of the findings from this study for siRNA delivery are discussed. The methods reported here can be used to support the SAR screening of cationic lipids for siRNA delivery, and the information revealed through the study of the interaction between cationic lipids and biomembranes will contribute significantly to the design of more efficient siRNA delivery vehicles.

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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle

PubMed Central

Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue

2014-01-01

Objective(s): The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Materials and Methods: Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. Results: The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm2/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. Conclusion: These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen. PMID:25729544

Development, implementation, and evaluation of the Apollo model of pediatric rehabilitation service delivery.

PubMed

Camden, Chantal; Swaine, Bonnie; Tétreault, Sylvie; Bergeron, Sophie; Lambert, Carole

2013-05-01

This article presents the experience of a rehabilitation program that undertook the challenge to reorganize its services to address accessibility issues and improve service quality. The context in which the reorganization process occurred, along with the relevant literature justifying the need for a new service delivery model, and an historical perspective on the planning; implementation; and evaluation phases of the process are described. In the planning phase, the constitution of the working committee, the data collected, and the information found in the literature are presented. Apollo, the new service delivery model, is then described along with each of its components (e.g., community, group, and individual interventions). Actions and lessons learnt during the implementation of each component are presented. We hope by sharing our experiences that we can help others make informed decisions about service reorganization to improve the quality of services provided to children with disabilities, their families, and their communities.

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.

Quality of perinatal care services from the user's perspective: a Dutch study applies the World Health Organization's responsiveness concept.

PubMed

van der Kooy, Jacoba; Birnie, Erwin; Valentine, Nicole B; de Graaf, Johanna P; Denktas, Semiha; Steegers, Eric A P; Bonsel, Gouke J

2017-09-29

The concept of responsiveness was introduced by the World Health Organization (WHO) to address non-clinical aspects of service quality in an internationally comparable way. Responsiveness is defined as aspects of the way individuals are treated and the environment in which they are treated during health system interactions. The aim of this study is to assess responsiveness outcomes, their importance and factors influencing responsiveness outcomes during the antenatal and delivery phases of perinatal care. The Responsiveness in Perinatal and Obstetric Health Care Questionnaire was developed in 2009/10 based on the eight-domain WHO concept and the World Health Survey questionnaire. After ethical approval, a total of 171 women, who were 2 weeks postpartum, were recruited from three primary care midwifery practices in Rotterdam, the Netherlands, using face-to-face interviews. We dichotomized the original five ordinal response categories for responsiveness attainment as 'poor' and good responsiveness and analyzed the ranking of the domain performance and importance according to frequency scores. We used a series of independent variables related to health services and users' personal background characteristics in multiple logistic regression analyses to explain responsiveness. Poor responsiveness outcomes ranged from 5.9% to 31.7% for the antenatal phase and from 9.7% to 27.1% for the delivery phase. Overall for both phases, 'respect for persons' (Autonomy, Dignity, Communication and Confidentiality) domains performed better and were judged to be more important than 'client orientation' domains (Choice and Continuity, Prompt Attention, Quality of Basic Amenities, Social Consideration). On the whole, responsiveness was explained more by health-care and health related issues than personal characteristics. To improve responsiveness outcomes caregivers should focus on domains in the category 'client orientation'.

Development of Recombinant Human Growth Hormone (rhGH) sustained-release microspheres by a low temperature aqueous phase/aqueous phase emulsion method.

PubMed

Kang, Jian; Wu, Fei; Cai, Yunpeng; Xu, Mingxin; He, Mu; Yuan, Weien

2014-10-01

A novel method has been developed to protect Recombinant Human Growth Hormone (rhGH) in poly (lactic-co-glycolic acid) (PLGA) microspheres using an aqueous phase/aqueous phase emulsion and S/O/W multi-emulsion method. This method develops a novel rhGH sustained-release system, which is based on the combination of rhGH-loaded dextran microparticles and PLGA microspheres. The process to fabricate rhGH-loaded dextran microparticles involves an aqueous phase/aqueous phase emulsion system formed at the reduced temperature. RhGH was first dissolved in water together with dextran and polyethylene glycol, followed by stirring at the speed of 2000 rpm for 20-30s at 0°C, and then a freezing process could enable the dextran phase to separate from the continuous PEG phase and rhGH could preferentially be loaded with dextran. The sample after freezing and phase separation was then lyophilized to powder and washed with dichloromethane to remove the PEG. Once loaded in the dextran microparticles (1-4 μm in diameter), rhGH gained resistance to interface tensions and was encapsulated into PLGA microspheres without aggregation thereafter. RhGH released from PLGA microspheres was in a sustained manner with minimal burst and maximally reduced incomplete release in vitro. Single subcutaneous injection of rhGH-loaded PLGA microspheres to rats resulted in a stable plasma concentration for 30 days avoiding the drug concentration fluctuations after multiple injections of protein solutions. In a hypophysectomized rat model, the IGF-1 and bodyweight results showed that there were higher than the levels obtained for the sustained release formulation by W/O/W for 40 days. These results suggest that the microsphere delivery system had the potential to be an injectable depot for sustained-release of the biocompatible protein of rhGH. Copyright © 2014 Elsevier B.V. All rights reserved.

In vitro biotransformation rates in fish liver S9: effect of dosing techniques.

PubMed

Lee, Yung-Shan; Lee, Danny H Y; Delafoulhouze, Maximilien; Otton, S Victoria; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2014-08-01

In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [KOW ] =10(5.60) ) and benzo[a]pyrene (KOW  =10(6.04) ), whereas there were no statistical differences in pyrene (KOW  =10(5.18) ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals. © 2014 SETAC.

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

A global health delivery framework approach to epilepsy care in resource-limited settings.

PubMed

Cochran, Maggie F; Berkowitz, Aaron L

2015-11-15

The Global Health Delivery (GHD) framework (Farmer, Kim, and Porter, Lancet 2013;382:1060-69) allows for the analysis of health care delivery systems along four axes: a care delivery value chain that incorporates prevention, diagnosis, and treatment of a medical condition; shared delivery infrastructure that integrates care within existing healthcare delivery systems; alignment of care delivery with local context; and generation of economic growth and social development through the health care delivery system. Here, we apply the GHD framework to epilepsy care in rural regions of low- and middle-income countries (LMIC) where there are few or no neurologists. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitivity Analysis of Algan/GAN High Electron Mobility Transistors to Process Variation

DTIC Science & Technology

2008-02-01

delivery system gas panel including both hydride and alkyl delivery modules and the vent/valve configurations [14...Reactor Gas Delivery Systems A basic schematic diagram of an MOCVD reactor delivery gas panel is shown in Figure 13. The reactor gas delivery...system, or gas panel , consists of a network of stainless steel tubing, automatic valves and electronic mass flow controllers (MFC). There are separate

An Application of Queues to Offensive Support Indirect Fire Weapons Systems

DTIC Science & Technology

2005-01-01

weapons systems capability is founded on delivery systems, operational procedures, ammunition and technologies from the 1960s. The changing nature of...fire away from busy delivery systems to less busy delivery systems by calculating the comparative estimation of busyness as given in equation (17... changes in the battlefield. Ideally, the delivery systems could be provided with 9 DSTO-TR-1662 Track of gun movements (100 cals-for-lire) 100 90 so 70 60

Data Management for Mars Exploration Rovers

NASA Technical Reports Server (NTRS)

Snyder, Joseph F.; Smyth, David E.

2004-01-01

Data Management for the Mars Exploration Rovers (MER) project is a comprehensive system addressing the needs of development, test, and operations phases of the mission. During development of flight software, including the science software, the data management system can be simulated using any POSIX file system. During testing, the on-board file system can be bit compared with files on the ground to verify proper behavior and end-to-end data flows. During mission operations, end-to-end accountability of data products is supported, from science observation concept to data products within the permanent ground repository. Automated and human-in-the-loop ground tools allow decisions regarding retransmitting, re-prioritizing, and deleting data products to be made using higher level information than is available to a protocol-stack approach such as the CCSDS File Delivery Protocol (CFDP).

An innovation for improving maternal, newborn and child health (MNCH) service delivery in Jigawa State, northern Nigeria: a qualitative study of stakeholders' perceptions about clinical mentoring.

PubMed

Okereke, Ekechi; Tukur, Jamilu; Aminu, Amina; Butera, Jean; Mohammed, Bello; Tanko, Mustapha; Yisa, Ibrahim; Obonyo, Benson; Egboh, Mike

2015-02-15

An effective capacity building process for healthcare workers is required for the delivery of quality health care services. Work-based training can be applied for the capacity building of health care workers while causing minimum disruption to service delivery within health facilities. In 2012, clinical mentoring was introduced into the Jigawa State Health System through collaboration between the Jigawa State Ministry of Health and the Partnership for Transforming Health Systems Phase 2 (PATHS2). This study evaluates the perceptions of different stakeholders about clinical mentoring as a strategy for improving maternal, newborn and child health service delivery in Jigawa State, northern Nigeria. Interviews were conducted in February 2013 with different stakeholders within Jigawa State in Northern Nigeria. There were semi-structured interviews with 33 mentored health care workers as well as the health facility departmental heads for Obstetrics and Pediatrics in the selected clinical mentoring health facilities. In-depth interviews were also conducted with the clinical mentors and two senior government health officials working within the Jigawa State Ministry of Health. The qualitative data were audio-recorded; transcribed and thematically analysed. The study findings suggest that clinical mentoring improved service delivery within the clinical mentoring health facilities. Significant improvements in the professional capacity of mentored health workers were observed by clinical mentors, heads of departments and the mentored health workers. Best practices were introduced with the support of the clinical mentors such as appropriate baseline investigations for pediatric patients, the use of magnesium sulphate and misoprostol for the management of eclampsia and post-partum hemorrhage respectively. Government health officials indicate that clinical mentoring has led to more emphasis on the need for the provision of better quality health services. Stakeholders report that the introduction of clinical mentoring into the Jigawa State health system gave rise to an improved capacity of the mentored health care workers to deliver better quality maternal, newborn and child health services. It is anticipated that with a scale up of clinical mentoring, health outcomes will also significantly improve across northern Nigeria.

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 luciferase reporter gene plasmid DNA. Prolonged expression was obtained for 9 days. PLGA and PLA-PEG microspheres were administered in vivo by intra-tracheal instillation and produced an acute inflammatory response, as observed from the large presence of neutrophils. The response using PLA-PEG microspheres yielded a lower total cell count signifying the incorporation of PEG into the copolymer backbone enhances the biocompatibility of the delivery system.

Effect of different polysorbates on development of self-microemulsifying drug delivery systems using medium chain lipids.

PubMed

Shah, Ankita; Thool, Prajwal; Sorathiya, Komal; Prajapati, Hetal; Dalrymple, Damon; Serajuddin, Abu T M

2018-02-01

The primary objective of this study was to develop lipid-based self-microemulsifying drug delivery systems (SMEDDS) without using any organic cosolvents that would spontaneously form microemulsions upon dilution with water. Cosolvents were avoided to prevent possible precipitation of drug upon dilution and other stability issues. Different polysorbates, namely, Tween 20, Tween 40, Tween 60, and Tween 80, were used as surfactants, and Captex 355 EP/NF (glycerol tricaprylate/caprate) or its 1:1 mixture with Capmul MCM NF (glycerol monocaprylocaprate) were used as lipids. Captex 355-Tween-water ternary phase diagrams showed that oil-in-water microemulsions were formed only when the surfactant content was high (80-90%) and the lipid content low (10-20%). Thus, mixtures of Tweens with Captex 355 alone were not suitable to prepare SMEDDS with substantial lipid contents. However, when Captex 355 was replaced with the 1:1 mixture of Captex 355 and Capmul MCM, clear isotropic microemulsion regions in phase diagrams with sizes in the increasing order of Tween 20 < Tween 40 < Tween 60 < Tween 80 were obtained. Tween 80 had the most profound effect among all surfactants as microemulsions were formed with lipid to surfactant ratios as high as 7:3, which may be attributed to the presence of double bond in its side chain that increased the curvature of surfactant layer. Thus, lipid-surfactant mixtures containing 1:1 mixture of medium chain triglyceride (Captex 355) and monoglyceride (Capmul MCM) and as low as 30% Tween 80 were identified as organic cosolvent-free systems for the preparation of SMEDDS. Formulations with a model drug, probucol, dispersed spontaneously and rapidly upon dilution with water to form microemulsions without any drug precipitation.

Developing a costing framework for palliative care services.

PubMed

Mosoiu, Daniela; Dumitrescu, Malina; Connor, Stephen R

2014-10-01

Palliative care services have been reported to be a less expensive alternative to traditional treatment; however, little is known about how to measure the cost of delivering quality palliative care. The purpose of this project was to develop a standardized method for measuring the cost of palliative care delivery that could potentially be replicated in multiple settings. The project was implemented in three stages. First, an interdisciplinary group of palliative care experts identified standards of quality palliative care delivery in the inpatient and home care services. Surveys were conducted of government agencies and palliative care providers to identify payment practices and budgets for palliative care services. In the second phase, unit costs were defined and a costing framework was designed to measure inpatient and home-based palliative care unit costs. The final phase was advocacy for inclusion of calculated costs into the national funding system. In this project, a reliable framework for determining the cost of inpatient and home-based palliative care services was developed. Inpatient palliative care cost in Romania was calculated at $96.58 per day. Home-based palliative care was calculated at $30.37 per visit, $723.60 per month, and $1367.71 per episode of care, which averaged 45 visits. A standardized methodology and framework for costing palliative care are presented. The framework allows a country or provider of care to substitute their own local costs to generate cost information relevant to the health-care system. In Romania, this allowed the palliative care provider community to advocate for a consistent payment system. Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and Transdermal Application.

PubMed

Jain, Shashank; Patel, Niketkumar; Shah, Mansi K; Khatri, Pinak; Vora, Namrata

2017-02-01

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid-based delivery systems (vesicular carriers and lipid particulate systems) have been the most successful. Vesicular carriers consist of liposomes, ultradeformable liposomes, and ethosomes, while lipid particulate systems consist of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers. These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Wall shear stress effects of different endodontic irrigation techniques and systems.

PubMed

Goode, Narisa; Khan, Sara; Eid, Ashraf A; Niu, Li-na; Gosier, Johnny; Susin, Lisiane F; Pashley, David H; Tay, Franklin R

2013-07-01

This study examined débridement efficacy as a result of wall shear stresses created by different irrigant delivery/agitation techniques in an inaccessible recess of a curved root canal model. A reusable, curved canal cavity containing a simulated canal fin was milled into mirrored titanium blocks. Calcium hydroxide (Ca(OH)2) paste was used as debris and loaded into the canal fin. The titanium blocks were bolted together to provide a fluid-tight seal. Sodium hypochlorite was delivered at a previously-determined flow rate of 1 mL/min that produced either negligible or no irrigant extrusion pressure into the periapex for all the techniques examined. Nine irrigation delivery/agitation techniques were examined: NaviTip passive irrigation control, Max-i-Probe(®) side-vented needle passive irrigation, manual dynamic agitation (MDA) using non-fitting and well-fitting gutta-percha points, EndoActivator™ sonic agitation with medium and large points, VPro™ EndoSafe™ irrigation system, VPro™ StreamClean™ continuous ultrasonic irrigation and EndoVac apical negative pressure irrigation. Débridement efficacies were analysed with Kruskal-Wallis ANOVA and Dunn's multiple comparisons tests (α=0.05). EndoVac was the only technique that removed more than 99% calcium hydroxide debris from the canal fin at the predefined flow rate. This group was significantly different (p<0.05) from the other groups that exhibited incomplete Ca(OH)2 removal. The ability of the EndoVac system to significantly clean more debris from a mechanically inaccessible recess of the model curved root canal may be caused by robust bubble formation during irrigant delivery, creating higher wall shear stresses by a two-phase air-liquid flow phenomenon that is well known in other industrial débridement systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Systemic inflammatory responses in progressing periodontitis during pregnancy in a baboon model

PubMed Central

Ebersole, J L; Steffen, M J; Holt, S C; Kesavalu, L; Chu, L; Cappelli, D

2010-01-01

This study tested the hypothesis that pregnant female baboons exhibit increased levels of various inflammatory mediators in serum resulting from ligature-induced periodontitis, and that these profiles would relate to periodontal disease severity/extent in the animals. The animals were sampled at baseline (B), mid-pregnancy (MP; two quadrants ligated) and at delivery (D; four quadrants ligated). All baboons developed increased plaque, gingival inflammation and bleeding, pocket depths and attachment loss following placement of the ligatures. By MP, both prostaglandin E2 (PGE2) and bactericidal permeability inducing factor (BPI) were greater than baseline, while increased levels of interleukin (IL)-6 occurred in the experimental animals by the time of delivery. IL-8, MCP-1 and LBP all decreased from baseline through the ligation phase of the study. Stratification of the animals by baseline clinical presentation demonstrated that PGE2, LBP, IL-8 and MCP-1 levels were altered throughout the ligation interval, irrespective of baseline clinical values. IL-6, IL-8 and LBP were significantly lower in the subset of animals that demonstrated the least clinical response to ligation, indicative of progressing periodontal disease. PGE2, macrophage chemotactic protein (MCP)-1, regulated upon activation, normal T cell expressed and secreted (RANTES) and LBP were decreased in the most diseased subset of animals at delivery. Systemic antibody responses to Fusobacterium nucleatum, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Campylobacter rectus were associated most frequently with variations in inflammatory mediator levels. These results provide a profile of systemic inflammatory mediators during ligature-induced periodontitis in pregnant baboons. The relationship of the oral clinical parameters to systemic inflammatory responses is consistent with a contribution to adverse pregnancy outcomes in a subset of the animals. PMID:21070210

Contribution of partial pancreatectomy, systemic hormone delivery, and duct obliteration to glucose regulation in canine pancreas. Importance in pancreas transplantation.

PubMed

van der Burg, M P; Gooszen, H G; Guicherit, O R; Jansen, J B; Frölich, M; van Haastert, F A; Lamers, C B

1989-09-01

Our aim was to isolate and determine the contribution of partial pancreatectomy, systemic delivery of pancreatic hormones, and duct obliteration to glucose regulation after segmental pancreas transplantation in dogs. Fasting, postprandial, and intravenous glucose-stimulated glucose, insulin, glucagon, pancreatic polypeptide (PP), and cholecystokinin (CCK) and intravenous bombesin-stimulated PP levels were studied in beagles at three successive intervals in a crossover design. The first was 6 wk after partial (approximately 70%) pancreatectomy with intact regular enteric exocrine drainage from the duodenal pancreatic remnant, the next was 2 wk after venous transposition with systemic delivery of pancreatic hormones, and the third was 6 wk after in situ duct obliteration of the remnant. With partial pancreatectomy, K values were modestly diminished (30%), and a concomitant reduction of second-phase intravenous glucose-stimulated insulin release was observed. Other parameters were not significantly affected. Venous transposition doubled peripheral plasma levels of insulin under all conditions. Fasting glucose, PP, and CCK levels decreased slightly. Other parameters were not affected. Duct obliteration of the systemic draining pancreatic remnants seriously impaired glucose sensitivity, resulting in a 50% reduction of K values and fasting and sustained postprandial hyperglycemia (approximately 8 mM) and a 70-50% reduction (acute and overall responses, respectively) of intravenous glucose-stimulated insulin. Fasting hormone and postprandial insulin, glucagon, and CCK levels were not affected. The postprandial PP response was severely reduced, and bombesin-stimulated PP release was abolished by duct obliteration. We conclude that histological changes associated with duct obliteration are the major determinants of glucose regulation in segmental pancreas transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Current and emerging lipid-based systems for transdermal drug delivery.

PubMed

Singla, Sumeet K; Sachdeva, Vishal

2015-01-01

Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

Encapsulated Presentation: A New Paradigm of Blended Learning

ERIC Educational Resources Information Center

Rose, Richard; Ray, Jan

2011-01-01

This article is a presentation of a new mode of blended learning whose only goal is to enrich the quality of instruction in the face-to-face classroom through the simultaneous delivery of online and face-to-face components. Encapsulated presentation is the delivery of the entire presentation phase of a lesson in the classroom by electronic methods…

Solid self-nanoemulsifying drug delivery systems for oral delivery of polypeptide-k: Formulation, optimization, in-vitro and in-vivo antidiabetic evaluation.

PubMed

Garg, Varun; Kaur, Puneet; Singh, Sachin Kumar; Kumar, Bimlesh; Bawa, Palak; Gulati, Monica; Yadav, Ankit Kumar

2017-11-15

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of polypeptide-k (PPK) is reported with the aim to achieve its oral delivery. Box-Behnken design (BBD) was adopted to develop and optimize the composition of SNEDDS. Oleoyl polyoxyl-6 glycerides (A), Tween 80 (B), and diethylene glycol monoethyl ether (C) were used as oil, surfactant and co-surfactant, respectively as independent variables. The effect of variation in their composition was observed on the mean droplet size (y1), polydispersity index (PDI) (y2), % drug loading (y3) and zeta potential (y4). As per the optimal design, seventeen SNEDDS prototypes were prepared. The optimized composition of SNEDDS formulation was 25% v/v Oleoyl polyoxyl-6 glycerides, 37% v/v Tween 80, 38% v/v diethylene glycol monoethyl ether, and 3% w/v PPK. The optimized formulation revealed values of y1, y2, y3, and y4 as 31.89nm, 0.16, 73.15%, and -15.65mV, respectively. Further the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, disintegration and dissolution properties. Both, liquid and solid-SNEDDS have shown release of >90% within 10min. The formulation was found stable with change in pH, dilution, temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline PPK was observed in amorphous state in solid SNEDDS when characterized through DSC and PXRD studies. The biochemical, hematological and histopathological results of streptozotocin induced diabetic rats shown promising antidiabetic potential of PPK loaded in SNEDDS at its both the doses (i.e. 400mg/kg and 800mg/kg) as compared to its naïve form at both the doses. The study revealed successful formulation of SNEDDS for oral delivery of PPK. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides.

PubMed

Batista, Patrícia; Castro, Pedro M; Madureira, Ana Raquel; Sarmento, Bruno; Pintado, Manuela

2018-03-01

Bioactive proteins and peptides have been used with either prophylactic or therapeutic purposes, presenting inherent advantages as high specificity and biocompatibility. Nanocarriers play an important role in the stabilization of proteins and peptides, offering enhanced buccal permeation and protection while crossing the gastrointestinal tract. Moreover, preparation of nanoparticles as oral delivery systems for proteins/peptides may include tailored formulation along with functionalization aiming bioavailability enhancement of carried proteins or peptides. Oral delivery systems, namely buccal delivery systems, represent an interesting alternative route to parenteric delivery systems to carry proteins and peptides, resulting in higher comfort of administration and, therefore, compliance to treatment. This paper outlines an extensive overview of the existing publications on proteins/peptides oral nanocarriers delivery systems, with special focus on buccal route. Manufacturing aspects of most commonly used nanoparticles for oral delivery (e.g. polymeric nanoparticles using synthetic or natural polymers and lipid nanoparticles) advantages and limitations and potential applications of nanoparticles as proteins/peptides delivery systems will also be thoroughly addressed. Copyright © 2018 Elsevier Inc. All rights reserved.

Creating a Learning Culture for Medical Consortia in China.

PubMed

He, Guozhong; Chen, Zimin

In China's recent health care reforms, both individuals and organizations have shown an ever-growing desire and demand for new knowledge and skills. A health care delivery system (HCDS) should explore new ways for creating a learning organization (LO) and should organically combine HCDS culture construction with the LO construction to build a cultural atmosphere that is conducive to the development of the LO. This article describes the implementation phase, characteristics, and realization strategy of an HCDS construction for the ultimate purpose of enhancing HCDS cohesion, solidarity, and sustainable development.

From "Frontiers of Astronomy" to Astrobiology

NASA Astrophysics Data System (ADS)

Kwok, Sun

2011-10-01

In his book Frontiers of Astronomy, Fred Hoyle outlined a number of ideas on the stellar synthesis of solid-state materials and their ejection into the interstellar medium. He also considered the possibility of interstellar organics being integrated into the early Earth during the accretion phase of planetary formation. These organics may have played a role in the origin of life and the creation of fossil fuels. In this paper, we assess these ideas with modern observational evidence, in particular on the evidence of stellar synthesis of complex organics and their delivery to the early Solar System.