A transient thermal model of a neutral buoyancy cryogenic fluid delivery system

NASA Astrophysics Data System (ADS)

Bue, Grant C.; Conger, Bruce S.

A thermal-performance model is presently used to evaluate a preliminary Neutral Buoyancy Cryogenic fluid-delivery system for underwater EVA training. Attention is given to the modeling of positional transients generated from the moving of internal components, including the control of cycling artifacts, as well as to the convection and boiling characteristics of the cryofluid, 250-psi N2/O2 gas, and water contained in the tank. Two piston designs are considered according to performance criteria; temperature and heat-transfer rate profiles are presented.

Miniature DMFCs with passive thermal-fluids management system

NASA Astrophysics Data System (ADS)

Guo, Zhen; Faghri, Amir

A new miniature DMFC system that includes a fuel cell stack, a fuel tank and a passive ancillary system (termed "thermal-fluids management system" in this paper) is presented. The thermal-fluids management system utilizes passive approaches for fuel storage and delivery, air breathing, water management, CO 2 release and thermal management. With 5.1 g of neat methanol in the fuel cartridge, a prototype has successfully demonstrated 18 h of continuous operation with total power output of 1.56 Wh.

Engine lubrication circuit including two pumps

DOEpatents

Lane, William H.

2006-10-03

A lubrication pump coupled to the engine is sized such that the it can supply the engine with a predetermined flow volume as soon as the engine reaches a peak torque engine speed. In engines that operate predominately at speeds above the peak torque engine speed, the lubrication pump is often producing lubrication fluid in excess of the predetermined flow volume that is bypassed back to a lubrication fluid source. This arguably results in wasted power. In order to more efficiently lubricate an engine, a lubrication circuit includes a lubrication pump and a variable delivery pump. The lubrication pump is operably coupled to the engine, and the variable delivery pump is in communication with a pump output controller that is operable to vary a lubrication fluid output from the variable delivery pump as a function of at least one of engine speed and lubrication flow volume or system pressure. Thus, the lubrication pump can be sized to produce the predetermined flow volume at a speed range at which the engine predominately operates while the variable delivery pump can supplement lubrication fluid delivery from the lubrication pump at engine speeds below the predominant engine speed range.

Fluid delivery manifolds and microfluidic systems

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

Renzi, Ronald F.; Sommer, Gregory J.; Singh, Anup K.

2017-02-28

Embodiments of fluid distribution manifolds, cartridges, and microfluidic systems are described herein. Fluid distribution manifolds may include an insert member and a manifold base and may define a substantially closed channel within the manifold when the insert member is press-fit into the base. Cartridges described herein may allow for simultaneous electrical and fluidic interconnection with an electrical multiplex board and may be held in place using magnetic attraction.

Strategies for Enhanced Drug Delivery to the Central Nervous System

PubMed Central

Dwibhashyam, V. S. N. M.; Nagappa, A. N.

2008-01-01

Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system. PMID:20046703

System Administration Support/SWORDS G2

NASA Technical Reports Server (NTRS)

Dito, Scott Joseph

2014-01-01

The Soldier-Warfighter Operationally Responsive Deployer for Space (SWORDS) rocket is a dedicated small satellite launcher that will minimize danger and complexity in order to allow soldiers in the field to put payloads of up to 25kg into orbit from the field. The SWORDSG2 project is the development of a model, simulation, and ultimately a working application that will control and monitor the cryogenic fluid delivery to the SWORDS rocket for testing purposes. To accomplish this, the project is using the programming language environment Gensym G2. The environment is an all-inclusive application that allows development, testing, modeling, and finally operation of the unique application through graphical and programmatic methods. In addition, observation of the current cryogenic fluid delivery system in the Kennedy Space Center Cry Lab has allowed me to gain valuable experience of fluid systems and propelant delivery that is valuable to our team when developing amd modeling our own system.The ultimate goal of having a test-ready application to show to the heads of the project, and demonstrating G2's capabilities, by late 2014 will require hard work and intense study and understanding of not only the programming aspect but also the physical phenomena we want to model, observe, and control.

Design, modeling and simulation of MEMS-based silicon Microneedles

NASA Astrophysics Data System (ADS)

Amin, F.; Ahmed, S.

2013-06-01

The advancement in semiconductor process engineering and nano-scale fabrication technology has made it convenient to transport specific biological fluid into or out of human skin with minimum discomfort. Fluid transdermal delivery systems such as Microneedle arrays are one such emerging and exciting Micro-Electro Mechanical System (MEMS) application which could lead to a total painless fluid delivery into skin with controllability and desirable yield. In this study, we aimed to revisit the problem with modeling, design and simulations carried out for MEMS based silicon hollow out of plane microneedle arrays for biomedical applications particularly for transdermal drug delivery. An approximate 200 μm length of microneedle with 40 μm diameter of lumen has been successfully shown formed by isotropic and anisotropic etching techniques using MEMS Pro design tool. These microneedles are arranged in size of 2 × 4 matrix array with center to center spacing of 750 μm. Furthermore, comparisons for fluid flow characteristics through these microneedle channels have been modeled with and without the contribution of the gravitational forces using mathematical models derived from Bernoulli Equation. Physical Process simulations have also been performed on TCAD SILVACO to optimize the design of these microneedles aligned with the standard Si-Fabrication lines.

Turbine airfoil cooling system with cooling systems using high and low pressure cooling fluids

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

Marsh, Jan H.; Messmann, Stephen John; Scribner, Carmen Andrew

A turbine airfoil cooling system including a low pressure cooling system and a high pressure cooling system for a turbine airfoil of a gas turbine engine is disclosed. In at least one embodiment, the low pressure cooling system may be an ambient air cooling system, and the high pressure cooling system may be a compressor bleed air cooling system. In at least one embodiment, the compressor bleed air cooling system in communication with a high pressure subsystem that may be a snubber cooling system positioned within a snubber. A delivery system including a movable air supply tube may be usedmore » to separate the low and high pressure cooling subsystems. The delivery system may enable high pressure cooling air to be passed to the snubber cooling system separate from low pressure cooling fluid supplied by the low pressure cooling system to other portions of the turbine airfoil cooling system.« less

Development of a gastroretentive pulsatile drug delivery platform.

PubMed

Thitinan, Sumalee; McConville, Jason T

2012-04-01

To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Comparison of life cycle emissions and energy consumption for environmentally adapted metalworking fluid systems.

PubMed

Clarens, Andres F; Zimmerman, Julie B; Keoleian, Greg A; Hayes, Kim F; Skerlos, Steven J

2008-11-15

A number of environmentally adapted lubricants have been proposed in response to the environmental and health impacts of metalworking fluids (MWFs). The alternatives typically substitute petroleum with vegetable-based components and/or deliver minimum quantities of lubricant in gas rather than water, with the former strategy being more prevalent than the latter. A comparative life cycle assessment of water- and gas-based systems has shown that delivery of lubricants in air rather than water can reduce solid waste by 60%, water use by 90%, and aquatic toxicity by 80%, while virtually eliminating occupational health concerns. However, air-delivery of lubricants cannot be used for severe machining operations due to limitations of cooling and lubricant delivery. For such operations, lubricants delivered in supercritical carbon dioxide (scCO2) are effective while maintaining the health and environmental advantages of air-based systems. Although delivery conditions were found to significantly influence the environmental burdens of all fluids, energy consumption was relatively constant under expected operating conditions. Global warming potential (GWP) increased when delivering lubricants in gas rather than water though all classes of MWFs have low GWP compared with other factory operations. It is therefore concluded that the possibility of increased GWP when switching to gas-based MWFs is a reasonable tradeoff for definite and large reductions in aquatic toxicity, water use, solid waste, and occupational health risks.

A novel dissolution method for evaluation of polysaccharide based colon specific delivery systems: A suitable alternative to animal sacrifice.

PubMed

Singh, Sachin Kumar; Yadav, Ankit Kumar; Prudhviraj, G; Gulati, Monica; Kaur, Puneet; Vaidya, Yogyata

2015-06-20

The most extensively used test for predicting in-vivo release kinetics of a drug from its orally administered dosage forms is dissolution testing. For polysaccharide based, colon targeted oral delivery systems, the entire path of the gut traversed by the dosage form needs to be simulated for assessing its in-vivo dissolution pattern. This includes the dissolution testing sequentially in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). For SGF and SIF, simple and standardized composition is well-known. However, preparation of SCF requires addition of either the colonic contents of rodents or human faecal slurry. A method is proposed, wherein a mixture of five probiotics cultured in the presence of a prebiotic under anaerobic conditions is able to surrogate the colonic fluid. Release profiles of drug from colon targeted delivery systems in this medium were studied and compared to those generated in the conventionally used media containing rodent caecal contents and human faecal slurry. The results from the three studies were found to be quite similar. These findings suggest that the proposed medium may prove to be useful not only as a biorelevant and discriminatory method but may also help in achieving the 3Rs objective regarding the ethical use of animals. Copyright © 2015 Elsevier B.V. All rights reserved.

Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake.

PubMed

Baek, Jong-Suep; Cho, Cheong-Weon

2017-08-01

Curcumin has been reported to exhibit potent anticancer effects. However, poor solubility, bioavailability and stability of curcumin limit its in vivo efficacy for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising delivery system for the enhancement of bioavailability of hydrophobic drugs. However, burst release of drug from SLN in acidic environment limits its usage as oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic environment and enhance the bioavailability. The NCC-SLN exhibited suppressed burst release in simulated gastric fluid while sustained release was observed in simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin solution, respectively. These results suggest that NCC-SLN could be an efficient oral delivery system for curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

PubMed

Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

2015-01-01

Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

Exhaust gas recirculation system for an internal combustion engine

DOEpatents

Wu, Ko-Jen

2013-05-21

An exhaust gas recirculation system for an internal combustion engine comprises an exhaust driven turbocharger having a low pressure turbine outlet in fluid communication with an exhaust gas conduit. The turbocharger also includes a low pressure compressor intake and a high pressure compressor outlet in communication with an intake air conduit. An exhaust gas recirculation conduit fluidly communicates with the exhaust gas conduit to divert a portion of exhaust gas to a low pressure exhaust gas recirculation branch extending between the exhaust gas recirculation conduit and an engine intake system for delivery of exhaust gas thereto. A high pressure exhaust gas recirculation branch extends between the exhaust gas recirculation conduit and the compressor intake and delivers exhaust gas to the compressor for mixing with a compressed intake charge for delivery to the intake system.

Conceptual design of a closed loop nutrient solution delivery system for CELSS implementation in a micro-gravity environment

NASA Technical Reports Server (NTRS)

Schwartzkopf, Steven H.; Oleson, Mel W.; Cullingford, Hatice S.

1990-01-01

Described here are the results of a study to develop a conceptual design for an experimental closed loop fluid handling system capable of monitoring, controlling, and supplying nutrient solution to higher plants. The Plant Feeder Experiment (PFE) is designed to be flight tested in a microgravity environment. When flown, the PFX will provide information on both the generic problems of microgravity fluid handling and the specific problems associated with the delivery of the nutrient solution in a microgravity environment. The experimental hardware is designed to fit into two middeck lockers on the Space Shuttle, and incorporates several components that have previously been flight tested.

Goal-directed Fluid Therapy May Improve Hemodynamic Stability of Parturient with Hypertensive Disorders of Pregnancy Under Combined Spinal Epidural Anesthesia for Cesarean Delivery and the Well-being of Newborns

PubMed Central

Xiao, Wei; Duan, Qing-Fang; Fu, Wen-Ya; Chi, Xin-Zuo; Wang, Feng-Ying; Ma, Da-Qing; Wang, Tian-Long; Zhao, Lei

2015-01-01

Background: Hypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy (HDP) can easily compromise blood supply to vital organs including uteroplacental perfusion and result in fetal distress. The aim of this study was to investigate whether the goal-directed fluid therapy (GDFT) with LiDCOrapid system can improve well-being of both HDP parturient and their babies. Methods: Fifty-two stable HDP parturient scheduled for elective cesarean delivery were recruited. After loading with 10 ml/kg lactated Ringer's solution (LR), parturient were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was guided by increase in stroke volume (ΔSV) provided via LiDCOrapid system. The control group received the routine fluid therapy. The primary endpoints included maternal hypotension and the doses of vasopressors administered prior to fetal delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events. Results: The severity of HDP was similar between two groups. The total LR infusion (P < 0.01) and urine output (P < 0.05) were higher in the GDFT group than in the control group. Following twice fluid challenge tests, the systolic blood pressure, mean blood pressure, cardiac output and SV in the GDFT group were significantly higher, and the heart rate was lower than in the control group. The incidence of maternal hypotension and doses of phenylephrine used prior to fetal delivery were significantly higher in the control group than in the GDFT group (P < 0.01). There were no differences in the Apgar scores between two groups. In the control group, the mean values of pH in umbilical artery/vein were remarkably decreased (P < 0.05), and the incidences of neonatal hypercapnia and hypoxemia were statistically increased (P < 0.05) than in the GDFT group. Conclusions: Dynamic responsiveness guided fluid therapy with the LiDCOrapid system may provide potential benefits to stable HDP parturient and their babies. PMID:26168834

Goal-directed Fluid Therapy May Improve Hemodynamic Stability of Parturient with Hypertensive Disorders of Pregnancy Under Combined Spinal Epidural Anesthesia for Cesarean Delivery and the Well-being of Newborns.

PubMed

Xiao, Wei; Duan, Qing-Fang; Fu, Wen-Ya; Chi, Xin-Zuo; Wang, Feng-Ying; Ma, Da-Qing; Wang, Tian-Long; Zhao, Lei

2015-07-20

Hypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy (HDP) can easily compromise blood supply to vital organs including uteroplacental perfusion and result in fetal distress. The aim of this study was to investigate whether the goal-directed fluid therapy (GDFT) with LiDCO rapid system can improve well-being of both HDP parturient and their babies. Fifty-two stable HDP parturient scheduled for elective cesarean delivery were recruited. After loading with 10 ml/kg lactated Ringer's solution (LR), parturient were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was guided by increase in stroke volume (ΔSV) provided via LiDCO rapid system. The control group received the routine fluid therapy. The primary endpoints included maternal hypotension and the doses of vasopressors administered prior to fetal delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events. The severity of HDP was similar between two groups. The total LR infusion (P < 0.01) and urine output (P < 0.05) were higher in the GDFT group than in the control group. Following twice fluid challenge tests, the systolic blood pressure, mean blood pressure, cardiac output and SV in the GDFT group were significantly higher, and the heart rate was lower than in the control group. The incidence of maternal hypotension and doses of phenylephrine used prior to fetal delivery were significantly higher in the control group than in the GDFT group (P < 0.01). There were no differences in the Apgar scores between two groups. In the control group, the mean values of pH in umbilical artery/vein were remarkably decreased (P < 0.05), and the incidences of neonatal hypercapnia and hypoxemia were statistically increased (P < 0.05) than in the GDFT group. Dynamic responsiveness guided fluid therapy with the LiDCO rapid system may provide potential benefits to stable HDP parturient and their babies.

Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier

PubMed Central

Strazielle, Nathalie; Ghersi-Egea, Jean-François

2016-01-01

The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates. PMID:27464721

Criteria for choosing an intravenous infusion line intended for multidrug infusion in anaesthesia and intensive care units.

PubMed

Maiguy-Foinard, Aurélie; Genay, Stéphanie; Lannoy, Damien; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal; Décaudin, Bertrand

2017-02-01

The aims are to identify critical parameters influencing the drug mass flow rate of infusion delivery to patients during multidrug infusion and to discuss their clinical relevance. A review of literature was conducted in January 2016 using Medline, Google Scholar, ScienceDirect, Web of Science and Scopus online databases. References relating to the accuracy of fluid delivery via gravity-flow intravenous (IV) infusion systems and positive displacement pumps, components of IV administration sets, causes of flow rate variability, potential complications due to flow rate variability, IV therapies especially at low flow rates and drug compatibilities were considered relevant. Several parameters impact the delivery of drugs and fluids by IV infusion. Among them are the components of infusion systems that particularly influence the flow rate of medications and fluids being delivered. By their conception, they may generate significant start-up delays and flow rate variability. Performing multidrug infusion requires taking into account two main points: the common dead volume of drugs delivered simultaneously with potential consequences on the accuracy and amount of drug delivery and the prevention of drug incompatibilities and their clinical effects. To prevent the potentially serious effects of flow rate variability on patients, clinicians should receive instruction on the fluid dynamics of an IV administration set and so be able to take steps to minimise flow rate changes during IV therapy. Copyright © 2016 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Early- or mid-trimester amniocentesis biomarkers for predicting preterm delivery: a meta-analysis.

PubMed

Liu, Yinglin; Liu, Yukun; Zhang, Rui; Zhu, Liqiong; Feng, Ziya

2017-02-01

To determine the value of early- or mid-trimester amniotic fluid levels of interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8), and glucose for predicting preterm delivery. Randomized controlled trials and two-arm prospective, retrospective, cohorts, and case-controlled studies in which patients received early- or mid-trimester amniocentesis for karyotyping, and biomarker testing of the amniotic fluid was performed and delivery data were available were included in the analysis. Outcome measures were the associations of amniotic fluid IL-6, MMP-8, and glucose levels with preterm delivery. Differences in means with 95% confidence intervals (CIs) were calculated. Of 288 articles identified, 14 were included in the meta-analysis with a total of 675 patients who had preterm birth and 2518 patients who had term births. The preterm-delivery group had significantly higher amniotic fluid IL-6 and MMP-8 levels, and a significantly lower glucose level than the term delivery group (IL-6: difference in means = 0.32, 95% CI: 0.22-0.43, p < 0.001; MMP-8: difference in means = 4.47, 95% CI: 0.83-8.11), p = 0.016; glucose: difference in means = -5.22, 95% CI: -8.19 to -2.26, p = 0.001) Conclusion: Early- or mid-trimester amniotic fluid IL-6, MMP-8, and glucose levels are useful for predicting the risk of preterm delivery. KEY MESSAGES Median amniotic fluid ferritin and IL-6 levels, and mean amniotic fluid ALP levels were higher in the preterm group. The preterm-delivery group had significantly higher amniotic fluid IL-6 and MMP-8 levels, and a significantly lower glucose level than the term-delivery group.

Fully Automated Anesthesia, Analgesia and Fluid Management

ClinicalTrials.gov

2017-01-03

General Anesthetic Drug Overdose; Adverse Effect of Intravenous Anesthetics, Sequela; Complication of Anesthesia; Drug Delivery System Malfunction; Hemodynamic Instability; Underdosing of Other General Anesthetics

Three dimensional transient multifield analysis of a piezoelectric micropump for drug delivery system for treatment of hemodynamic dysfunctions.

PubMed

Nisar, Asim; Afzulpurkar, Nitin; Tuantranont, Adisorn; Mahaisavariya, Banchong

2008-12-01

In this paper, we present design of a transdermal drug delivery system for treatment of cardiovascular or hemodynamic disorders such as hypertension. The system comprises of integrated control electronics and microelectromechanical system devices such as micropump, micro blood pressure sensor and microneedle array. The objective is to overcome the limitations of oral therapy such as variable absorption profile and the need for frequent dosing, by fabricating a safe, reliable and cost effective transdermal drug delivery system to dispense various pharmacological agents through the skin for treatment of hemodynamic dysfunction such as hypertension. Moreover, design optimization of a piezoelectrically actuated valveless micropump is presented for the drug delivery system. Because of the complexity in analysis of piezoelectric micropump, which involves structural and fluid field couplings in a complicated geometrical arrangement, finite element (FE) numerical simulation rather than an analytical system has been used. The behavior of the piezoelectric actuator with biocompatible polydimethylsiloxane membrane is first studied by conducting piezoelectric analysis. Then the performance of the valveless micropump is analyzed by building a three dimensional electric-solid-fluid model of the micropump. The effect of geometrical dimensions on micropump characteristics and efficiency of nozzle/diffuser elements of a valveless micropump is investigated in the transient analysis using multiple code coupling method. The deformation results of the membrane using multifield code coupling analysis are in good agreement with analytical as well as results of single code coupling analysis of a piezoelectric micropump. The analysis predicts that to enhance the performance of the micropump, diffuser geometrical dimensions such as diffuser length, diffuser neck width and diffuser angle need to be optimized. Micropump flow rate is not strongly affected at low excitation frequencies from 10 to 200 Hz. The excitation voltage is the more dominant factor that affects the flow rate of the micropump as compared with the excitation frequency. However, at extremely high excitation frequencies beyond 8,000 Hz, the flow rate drops as the membrane exhibits multiple bending peaks which is not desirable for fluid flow. Following the extensive numerical analysis, actual fabrication and performance characterization of the micropump is presented. The performance of the micropump is characterized in terms of piezoelectric actuator deflection and micropump flow rate at different operational parameters. The set of multifield simulations and experimental measurement of deflection and flow rate at varying voltage and excitation frequency is a significant advance in the study of the electric-solid-fluid coupled field effects as it allows transient, three dimensional piezoelectric and fluid analysis of the micropump thereby facilitating a more realistic multifield analysis. The results of the present study will also help to conduct relevant strength duration tests of integrated drug delivery device with micropump and microneedle array in future.

Multishell encapsulation using a triple coaxial electrospray system.

PubMed

Kim, Woojin; Kim, Sang Soo

2010-06-01

To overcome the limitations of the conventional encapsulation methods and improve the potential use of the electrospray method as a drug delivery system, an electrospray system using a triple coaxial nozzle was developed to generate multishell capsules. Two conducting fluids, ethylene glycol and 4-hydroxybutyl acrylate, and one nonconducting fluid, olive oil, were chosen to manufacture the multishell capsules. The capsules were solidified by a photopolymerization device. We investigated the size distributions and visualized the capsules changing fluid flow rates. Dispersive Raman spectra were also monitored to determine the chemical composition of the capsules. The multishell capsules were generated in the overlapped cone-jet mode regime of the conducting fluids, and the sizes and shell thicknesses were controlled by the flow rates and applied voltages.

The Direction of Fluid Dynamics for Liquid Propulsion at NASA Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Griffin, Lisa W.

2012-01-01

Marshall Space Flight Center (MSFC) is the National Aeronautics and Space Administration (NASA)-designated center for the development of space launch systems. MSFC is particularly known for propulsion system development. Many engineering skills and technical disciplines are needed to accomplish this mission. This presentation will focus on the work of the Fluid Dynamics Branch (ER42). ER42 resides in the Propulsion Systems Department at MSFC. The branch is responsible for all aspects of the discipline of fluid dynamics applied to propulsion or propulsion-induced loads and environments. This work begins with design trades and parametric studies, and continues through development, risk assessment, anomaly investigation and resolution, and failure investigations. Applications include the propellant delivery system including the main propulsion system (MPS) and turbomachinery; combustion devices for liquid engines and solid rocket motors; coupled systems; and launch environments. An advantage of the branch is that it is neither analysis nor test centric, but discipline centric. Fluid dynamics assessments are made by analysis, from lumped parameter modeling through unsteady computational fluid dynamics (CFD); testing, which can be cold flow or hot fire; or a combination of analysis and testing. Integration of all discipline methods into one branch enables efficient and accurate support to the projects. To accomplish this work, the branch currently employs approximately fifty engineers divided into four teams -- Propellant Delivery CFD, Combustion Driven Flows CFD, Unsteady and Experimental Flows, and Acoustics and Stability. This discussion will highlight some of the work performed in the branch and the direction in which the branch is headed.

Capillary Flow Experiment

NASA Image and Video Library

2014-06-19

ISS040-E-015539 (19 June 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, conducts a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the CFE-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Characteristics of lipid micro- and nanoparticles based on supercritical formation for potential pharmaceutical application

PubMed Central

2013-01-01

The interest of the pharmaceutical industry in lipid drug delivery systems due to their prolonged release profile, biocompatibility, reduction of side effects, and so on is already known. However, conventional methods of preparation of these structures for their use and production in the pharmaceutical industry are difficult since these methods are usually multi-step and involve high amount of organic solvent. Furthermore, some processes need extreme conditions, which can lead to an increase of heterogeneity of particle size and degradation of the drug. An alternative for drug delivery system production is the utilization of supercritical fluid technique. Lipid particles produced by supercritical fluid have shown different physicochemical properties in comparison to lipid particles produced by classical methods. Such particles have shown more physical stability and narrower size distribution. So, in this paper, a critical overview of supercritical fluid-based processes for the production of lipid micro- and nanoparticles is given and the most important characteristics of each process are highlighted. PMID:24034341

The Direction of Fluid Dynamics for Liquid Propulsion at NASA Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Griffin, Lisa W.

2012-01-01

The Fluid Dynamics Branch's (ER42) at MSFC mission is to support NASA and other customers with discipline expertise to enable successful accomplishment of program/project goals. The branch is responsible for all aspects of the discipline of fluid dynamics, analysis and testing, applied to propulsion or propulsion-induced loads and environments, which includes the propellant delivery system, combustion devices, coupled systems, and launch and separation events. ER42 supports projects from design through development, and into anomaly and failure investigations. ER42 is committed to continually improving the state-of-its-practice to provide accurate, effective, and timely fluid dynamics assessments and in extending the state-of-the-art of the discipline.

CFE-2 ICF-9 Experiment

NASA Image and Video Library

2014-01-03

ISS038-E-025016 (3 Jan. 2014) --- NASA astronaut Rick Mastracchio, Expedition 38 flight engineer, conducts a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the CFE-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Capillary Flow Experiment

NASA Image and Video Library

2014-06-19

ISS040-E-015545 (19 June 2014) --- European Space Agency astronaut Alexander Gerst, Expedition 40 flight engineer, conducts a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the CFE-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Hopkins during CFE-2 Experiment

NASA Image and Video Library

2013-11-20

ISS038-E-005962 (19 Nov. 2013) --- NASA astronaut Michael Hopkins, Expedition 38 flight engineer, conducts a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the Capillary Flow Experiment-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Capillary Flow Experiment

NASA Image and Video Library

2014-06-19

ISS040-E-015532 (19 June 2014) --- European Space Agency astronaut Alexander Gerst, Expedition 40 flight engineer, conducts a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the CFE-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Capillary Flow Experiment

NASA Image and Video Library

2014-06-19

ISS040-E-015523 (19 June 2014) --- European Space Agency astronaut Alexander Gerst, Expedition 40 flight engineer, conducts a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the CFE-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Capillary Flow Experiment

NASA Image and Video Library

2014-06-19

ISS040-E-015543 (19 June 2014) --- European Space Agency astronaut Alexander Gerst, Expedition 40 flight engineer, conducts a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the CFE-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Capillary Flow Experiment

NASA Image and Video Library

2014-06-19

ISS040-E-015536 (19 June 2014) --- European Space Agency astronaut Alexander Gerst, Expedition 40 flight engineer, conducts a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the CFE-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Harnessing Electrostatic Forces to Grow Bio-inspired Hierarchical Vascular Networks

NASA Astrophysics Data System (ADS)

Behler, Kristopher; Melrose, Zachary; Schott, Andrew; Wetzel, Eric

2012-02-01

Vascular networks provide a system for fluid distribution. Artificial vascular materials with enhanced properties are currently being developed that could ultimately be integrated into systems reliant upon fluid transport while retaining their structural properties. An uninterrupted and controllable supply of liquid is optimal for many applications such as continual self-healing materials, in-situ delivery of index matched fluids, thermal management and drug delivery systems could benefit from a bio-inspired vascular approach that combines complex network geometries with minimal processing parameters. Two such approaches to induce vascular networks are electrohydrodynamic viscous fingering (EHVF) and electrical treeing (ET). EHVF is a phenomenon that occurs when a low viscosity liquid is forced through a high viscosity fluid or matrix, resulting in branches due to capillary and viscous forces in the high viscosity material. By applying voltages of 0 -- 60 kV, finger diameter is reduced. ET is the result of partial discharges in a dielectric material. In the vicinity of a small diameter electrode, the local electric field is greater than the global dielectric strength, causing a localized, step-wise, breakdown to occur forming a highly branched interconnected structure. ET is a viable method to produce networks on a smaller, micron, scale than the products of the EHVF method.

Variable delivery, fixed displacement pump

DOEpatents

Sommars, Mark F.

2001-01-01

A variable delivery, fixed displacement pump comprises a plurality of pistons reciprocated within corresponding cylinders in a cylinder block. The pistons are reciprocated by rotation of a fixed angle swash plate connected to the pistons. The pistons and cylinders cooperate to define a plurality of fluid compression chambers each have a delivery outlet. A vent port is provided from each fluid compression chamber to vent fluid therefrom during at least a portion of the reciprocal stroke of the piston. Each piston and cylinder combination cooperates to close the associated vent port during another portion of the reciprocal stroke so that fluid is then pumped through the associated delivery outlet. The delivery rate of the pump is varied by adjusting the axial position of the swash plate relative to the cylinder block, which varies the duration of the piston stroke during which the vent port is closed.

Magnetite Nanoparticles Coated with Rifampicin and Chlortetracycline for Drug Delivery Applications

NASA Astrophysics Data System (ADS)

Nǎdejde, Claudia; Ciurlicǎ, Ecaterina Foca-nici; Creangǎ, Dorina; Cârlescu, Aurelian; Bǎdescu, Vasile

2010-12-01

Four types of biocompatible magnetic fluids based on superparamagnetic nanoparticles with Fe3O4 cores were functionalized with antibiotics (rifampicin or chlortetracycline) as potential candidates for in vivo biomedical applications, such as magnetically controlled drug delivery. The synthesis consisted in coprecipitation of iron oxide in basic, as well as in acid medium, followed by the dispersion of the resulted magnetite nanoparticles in aqueous solution containing the antibiotic. The chosen method to prepare the magnetite-core/drug-shell systems avoided intermediate organic coating of the magnetic nanoparticles. Comparative analysis of the rheological features of the aqueous magnetic fluid samples was performed. The structural features of the coated magnetic particles were investigated by X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometry (VSM). Good crystallinity and adequate stability in time were evidenced. Drug delivery curves were spectrophotometrically provided.

A MEMS Electrochemical Bellows Actuator for Fluid Metering Applications

PubMed Central

Sheybani, Roya; Gensler, Heidi; Meng, Ellis

2013-01-01

We present a high efficiency wireless MEMS electrochemical bellows actuator capable of rapid and repeatable delivery of boluses for fluid metering and drug delivery applications. Nafion®-coated Pt electrodes were combined with Parylene bellows filled with DI water to form the electrolysis-based actuator. The performance of actuators with several bellows configurations was compared for a range of applied currents (1-10 mA). Up to 75 boluses were delivered with an average pumping flow rate of 114.40 ± 1.63 μL/min. Recombination of gases into water, an important factor in repeatable and reliable actuation, was studied for uncoated and Nafion®-coated actuators. Real-time pressure measurements were conducted and the effects of temperature, physiological back pressure, and drug viscosity on delivery performance were investigated. Lastly, we present wireless powering of the actuator using a class D inductive powering system that allowed for repeatable delivery with less than 2% variation in flow rate values. PMID:22833156

A liquid-delivery device that provides precise reward control for neurophysiological and behavioral experiments.

PubMed

Mitz, Andrew R

2005-10-15

Behavioral neurophysiology and other kinds of behavioral research often involve the delivery of liquid rewards to experimental subjects performing some kind of operant task. Available systems use gravity or pumps to deliver these fluids, but such methods are poorly suited to moment-to-moment control of the volume, timing, and type of fluid delivered. The design described here overcomes these limitations using an electronic control unit, a pressurized reservoir unit, and an electronically controlled solenoid. The control unit monitors reservoir pressure and provides precisely timed solenoid activation signals. It also stores calibration tables and does on-the-fly interpolation to support computer-controlled delivery calibrated directly in milliliters. The reservoir provides pressurized liquid to a solenoid mounted near the subject. Multiple solenoids, each supplied by a separate reservoir unit and control unit, can be stacked in close proximity to allow instantaneous selection of which liquid reward is delivered. The precision of droplet delivery was verified by weighing discharged droplets on a commercial analytical balance.

CFE-2 Experiment ICF-5 in the Node 2

NASA Image and Video Library

2014-01-03

ISS038-E-025000 (3 Jan. 2014) --- NASA astronaut Rick Mastracchio, Expedition 38 flight engineer, speaks in a microphone while conducting a session with the Capillary Flow Experiment (CFE-2) in the Harmony node of the International Space Station. CFE is a suite of fluid physics experiments that investigate how fluids behave in microgravity which could benefit water and fuel delivery systems on future spacecraft. Scientists designed the CFE-2 to study properties of fluids and bubbles inside containers with a specific 3-D geometry.

Novel biorelevant dissolution medium as a prognostic tool for polysaccharide-based colon-targeted drug delivery system.

PubMed

Yadav, Ankit Kumar; Sadora, Manik; Singh, Sachin Kumar; Gulati, Monica; Maharshi, Peddi; Sharma, Abhinav; Kumar, Bimlesh; Rathee, Harish; Ghai, Deepak; Malik, Adil Hussain; Garg, Varun; Gowthamrajan, K

2017-01-01

To overcome the limitations of the conventionally used methods for evaluation of orally administered colon-targeted delivery systems, a novel dissolution method using probiotics has been recently reported. In the present study, universal suitability of this medium composed of five different probiotics is established. Different delivery systems - mini tablets, liquisolid compacts, and microspheres coated with different polysaccharides - were prepared and subjected to sequential dissolution testing in medium with and without microbiota. The results obtained from fluid thioglycollate medium (FTM)-based probiotic medium for all the polysaccharide-based formulations showed statistically similar dissolution profile to that in the rat and goat cecal content media. Hence, it can be concluded that the developed FTM-based probiotic medium, once established, may eliminate the need for further animal sacrifice in the dissolution testing of polysaccharide-based colon-targeted delivery system.

Systemic complications of fluid resuscitation.

PubMed

Weinstein, P D; Doerfler, M E

1992-04-01

Fluid administration in critically ill individuals is frequently a major component of their therapy. There are important effects on blood pressure and maintenance of cardiac output and oxygen delivery, as detailed elsewhere in this text. There are also potentially negative side effects of this therapy, which have been less well defined. Edema of the gastrointestinal tract has been well described, primarily with crystalloid infusions. Gastrointestinal edema may have very complicated effects on albumin kinetics, fluid flux, and ion flux. It may lead to development of ileus. Increased nasogastric tube output may be incorrectly construed as unremitting obstruction rather than a result of the aforementioned changes and increased crystalloid loads. The relationships of intestinal edema to intestinal absorptive function and diarrhea are less clear. At present, changes in type of fluid infusion or correction of serum albumin level to normal cannot be uniformly recommended. The myocardium, although showing evidence of edema with crystalloid infusion, may appear to benefit from colloidal, osmotically active suspensions in the all too few studies that have been done. To date, there is no study giving evidence of clinically different outcome using a variety of fluids that cause, reduce, or prevent this edema. The presence or absence of myocardial edema may be important in patients who demonstrate decreased ventricular function during sepsis or other disorders in which aggressive fluid administration is routine. Edema of the skin has been associated primarily with decreased oxygen tension. Other studies have shown an association with impaired wound healing or increased risk of infection. A direct causal relationship can only be inferred. We are left with a sense that aggressive fluid resuscitation with crystalloid, although improving oxygen delivery, may have other deleterious effects on organ systems, such as the gastrointestinal tract, myocardium, and integument. The edema resulting from crystalloid administration may lessen or negate the benefits of increased oxygen delivery. Care needs to be taken in interpreting any alteration in organ function with respect to the fluid type and volume being administered. An alternative choice of therapy is lacking at present. The role of colloid has not been as well investigated as that of crystalloid and further study is warranted before any benefits become clear.

Feasibility study for the Cryogenic Orbital Nitrogen Experiment (CONE)

NASA Technical Reports Server (NTRS)

Bell, R. S.; Crouch, M. A.; Hanna, G. J.; Cady, E. C.; Meserole, J. S.

1991-01-01

An improved understanding of low gravity subcritical cryogenic fluid behavior is critical for the continued development of space based systems. Although early experimental programs provided some fundamental understanding of zero gravity cryogenic fluid behavior, more extensive flight data are required to design space based cryogenic liquid storage and transfer systems with confidence. As NASA's mission concepts evolve, the demand for optimized in-space cryogenic systems is increasing. Cryogenic Orbital Nitrogen Experiment (CONE) is an attached shuttle payload experiment designed to address major technological issues associated with on-orbit storage and supply of cryogenic liquids. During its 7 day mission, CONE will conduct experiments and technology demonstrations in active and passive pressure control, stratification and mixing, liquid delivery and expulsion efficiency, and pressurant bottle recharge. These experiments, conducted with liquid nitrogen as the test fluid, will substantially extend the existing low gravity fluid data base and will provide future system designers with vital performance data from an orbital environment.

Supercritical fluid technology: concepts and pharmaceutical applications.

PubMed

Deshpande, Praful Balavant; Kumar, G Aravind; Kumar, Averineni Ranjith; Shavi, Gopal Venkatesh; Karthik, Arumugam; Reddy, Meka Sreenivasa; Udupa, Nayanabhirama

2011-01-01

In light of environmental apprehension, supercritical fluid technology (SFT) exhibits excellent opportunities to accomplish key objectives in the drug delivery sector. Supercritical fluid extraction using carbon dioxide (CO(2)) has been recognized as a green technology. It is a clean and versatile solvent with gas-like diffusivity and liquid-like density in the supercritical phase, which has provided an excellent alternative to the use of chemical solvents. The present commentary provides an overview of different techniques using supercritical fluids and their future opportunity for the drug delivery industry. Some of the emerging applications of SFT in pharmaceuticals, such as particle design, drug solubilization, inclusion complex, polymer impregnation, polymorphism, drug extraction process, and analysis, are also covered in this review. The data collection methods are based on the recent literature related to drug delivery systems using SFT platforms. SFT has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This cutting-edge technology is growing predominantly to surrogate conventional unit operations in relevance to the pharmaceutical production process. Supercritical fluid technology has recently drawn attention in the field of pharmaceuticals. It is a distinct conception that utilizes the solvent properties of supercritical fluids above their critical temperature and pressure, where they exhibit both liquid-like and gas-like properties, which can enable many pharmaceutical applications. For example, the liquid-like properties provide benefits in extraction processes of organic solvents or impurities, drug solubilization, and polymer plasticization, and the gas-like features facilitate mass transfer processes. It has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This review is focused on different techniques that use supercritical fluids and their opportunities for the pharmaceutical sector.

Overcoming the Cutaneous Barrier with Microemulsions

PubMed Central

Lopes, Luciana B.

2014-01-01

Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

Injectable hydrogels for delivering biotherapeutic molecules.

PubMed

Mathew, Ansuja Pulickal; Uthaman, Saji; Cho, Ki-Hyun; Cho, Chong-Su; Park, In-Kyu

2018-04-15

To date, numerous delivery systems based on either organic or inorganic material have been developed to achieve efficient and sustained delivery of therapeutics. Hydrogels, which are three dimensional networks of crosslinked hydrophilic polymers, have a significant role in solving the clinical and pharmacological limitations of present systems because of their biocompatibility, ease of preparation and unique physical properties such as a tunable porous nature and affinity for biological fluids. Development of an in situ forming injectable hydrogel system has allowed excellent spatial and temporal control, unlike systemically administered therapeutics. Injectable hydrogel systems can offset difficulties with conventional hydrogel-based drug delivery systems in the clinic by forming a drug/gene delivery or cell-growing depot in the body with a single injection, thereby enabling patient compliance and comfort. Carbohydrate polymers are widely used for the synthesis of injectable in situ-forming hydrogels because of ready availability, presence of modifiable functional groups, biocompatibility and other physiochemical properties. In this review, we discuss different aspects of injectable hydrogels, such as bulk hydrogels/macrogels, microgels, and nanogels derived from natural polymers, and their importance in the delivery of therapeutics such as genes, drugs, cells or other biomolecules and how these revolutionary systems can complement existing therapeutic delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards an integrated optofluidic system for highly sensitive detection of antibiotics in seawater incorporating bimodal waveguide photonic biosensors and complex, active microfluidics

NASA Astrophysics Data System (ADS)

Szydzik, C.; Gavela, A. F.; Roccisano, J.; Herranz de Andrés, S.; Mitchell, A.; Lechuga, L. M.

2016-12-01

We present recent results on the realisation and demonstration of an integrated optofluidic lab-on-a-chip measurement system. The system consists of an integrated on-chip automated microfluidic fluid handling subsystem, coupled with bimodal nano-interferometer waveguide technology, and is applied in the context of detection of antibiotics in seawater. The bimodal waveguide (BMWG) is a highly sensitive label-free biosensor. Integration of complex microfluidic systems with bimodal waveguide technology enables on-chip sample handling and fluid processing capabilities and allows for significant automation of experimental processes. The on-chip fluid-handling subsystem is realised through the integration of pneumatically actuated elastomer pumps and valves, enabling high temporal resolution sample and reagent delivery and facilitating multiplexed detection processes.

The role of brain barriers in fluid movement in the CNS: is there a 'glymphatic' system?

PubMed

Abbott, N Joan; Pizzo, Michelle E; Preston, Jane E; Janigro, Damir; Thorne, Robert G

2018-03-01

Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with CNS microvessels, and, finally, a mixture of CSF/ISF/waste products is normally cleared along the PVS of venules/veins as well as other pathways; such a system may or may not constitute a true 'circulation', but, at the least, suggests a comprehensive re-evaluation of the previously proposed 'glymphatic' concepts in favour of a new system better taking into account basic cerebrovascular physiology and fluid transport considerations.

An oral oligonucleotide delivery system based on a thiolated polymer: Development and in vitro evaluation.

PubMed

Martien, Ronny; Hoyer, Herbert; Perera, Glen; Schnürch, Andreas Bernkop

2011-08-01

The purpose of this study was to develop and evaluate an oral oligonucleotide delivery system based on a thiolated polymer/reduced glutathione (GSH) system providing a protective effect toward nucleases and permeation enhancement. A polycarbophil-cysteine conjugate (PCP-Cys) was synthesized. Enzymatic degradation of a model oligonucleotide by DNase I and within freshly collected intestinal fluid was investigated in the absence and presence of PCP-Cys. Permeation studies with PCP-Cys/GSH versus control were performed in vitro on Caco-2 cell monolayers and ex vivo on rat intestinal mucosa. PCP-Cys displayed 223 ± 13.8 μmol thiol groups per gram polymer. After 4h, 61% of the free oligonucleotides were degraded by DNase I and 80% within intestinal fluid. In contrast, less than 41% (DNase I) and 60% (intestinal fluid) were degraded in the presence of 0.02% (m/v) PCP-Cys. Permeation studies revealed an 8-fold (Caco-2) and 10-fold (intestinal mucosa) increase in apparent permeability compared to buffer control. Hence, this PCP-Cys/GSH system might be a promising tool for the oral administration of oligonucleotides as it allows a significant protection toward degrading enzymes and facilitates their transport across intestinal membranes. Copyright © 2011 Elsevier B.V. All rights reserved.

Precise nanoliter fluid handling system with integrated high-speed flow sensor.

PubMed

Haber, Carsten; Boillat, Marc; van der Schoot, Bart

2005-04-01

A system for accurate low-volume delivery of liquids in the micro- to nanoliter range makes use of an integrated miniature flow sensor as part of an intelligent feedback control loop driving a micro-solenoid valve. The flow sensor is hydraulically connected with the pressurized system liquid in the dispensing channel and located downstream from the pressure source, above the solenoid valve. The sensor operates in a differential mode and responds in real-time to the internal flow-pulse resulting from the brief opening interval of the solenoid valve leading to a rapid ejection of a fluid droplet. The integral of the flow-pulse delivered by the sensor is directly proportional to the volume of the ejected droplet from the nozzle. The quantitative information is utilized to provide active control of the effectively dispensed or aspirated volume by adjusting the solenoid valve accordingly. This process significantly enhances the precision of the fluid delivery. The system furthermore compensates automatically for any changes in the viscosity of the dispensed liquid. The data delivered by the flow sensor can be saved and backtracked in order to confirm and validate the aspiration and dispensing process in its entirety. The collected dispense information can be used for quality control assessments and automatically be made part of an electronic record.

Goal-directed fluid therapy may improve hemodynamic stability in parturient women under combined spinal epidural anesthesia for cesarean section and newborn well-being.

PubMed

Xiao, Wei; Duan, Qingfang; Zhao, Lei; Chi, Xinzuo; Wang, Fengying; Ma, Daqing; Wang, Tianlong

2015-10-01

To investigate whether goal-directed fluid therapy (GDFT) with the LiDCOrapid system can reduce the incidence of maternal hypotension and improve neonatal outcome. One hundred healthy term parturient women scheduled for elective cesarean section were recruited. After loading with 10 mL/kg Lactated Ringer's solution, parturient women were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was implemented to optimize stroke volume, guided by the LiDCOrapid system. The control group received routine fluid therapy. Primary endpoints included onset of maternal hypotension, and vasopressor doses prior to delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events. Incidence of hypotension and mean phenylephrine dose administered prior to delivery were significantly higher in the control group than in the GDFT group (P < 0.01). There was no difference in Apgar score between the two groups. In the control group, mean umbilical artery and vein blood pH were significantly lower, corresponding to significantly higher incidences of neonatal hypercapnia and hypoxemia, compared with the GDFT group (P < 0.05). LiDCOrapid -guided GDFT may provide benefit to healthy parturient women and their newborns. © 2015 Japan Society of Obstetrics and Gynecology.

Non-Viral Nucleic Acid Delivery Strategies to the Central Nervous System

PubMed Central

Tan, James-Kevin Y.; Sellers, Drew L.; Pham, Binhan; Pun, Suzie H.; Horner, Philip J.

2016-01-01

With an increased prevalence and understanding of central nervous system (CNS) injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the CNS and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the CNS are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for CNS applications and will ultimately bring non-viral vectors closer to clinical application. PMID:27847462

Multiple pump housing

DOEpatents

Donoho, II, Michael R.; Elliott; Christopher M.

2010-03-23

A fluid delivery system includes a first pump having a first drive assembly, a second pump having a second drive assembly, and a pump housing. At least a portion of each of the first and second pumps are located in the housing.

Three-Stream, Bicarbonate-Based Hemodialysis Solution Delivery System Revisited: With an Emphasis on Some Aspects of Acid-Base Principles.

PubMed

Lew, Susie Q; Kohn, Orly F; Cheng, Yuk-Lun; Kjellstrand, Carl M; Ing, Todd S

2017-06-01

Hemodialysis patients can acquire buffer base (i.e., bicarbonate and buffer base equivalents of certain organic anions) from the acid and base concentrates of a three-stream, dual-concentrate, bicarbonate-based, dialysis solution delivery machine. The differences between dialysis fluid concentrate systems containing acetic acid versus sodium diacetate in the amount of potential buffering power were reviewed. Any organic anion such as acetate, citrate, or lactate (unless when combined with hydrogen) delivered to the body has the potential of being converted to bicarbonate. The prescribing physician aware of the role that organic anions in the concentrates can play in providing buffering power to the final dialysis fluid, will have a better knowledge of the amount of bicarbonate and bicarbonate precursors delivered to the patient. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Kinetics of reciprocating drug delivery to the inner ear.

PubMed

Pararas, Erin E Leary; Chen, Zhiqiang; Fiering, Jason; Mescher, Mark J; Kim, Ernest S; McKenna, Michael J; Kujawa, Sharon G; Borenstein, Jeffrey T; Sewell, William F

2011-06-10

Reciprocating drug delivery is a means of delivering soluble drugs directly to closed fluid spaces in the body via a single cannula without an accompanying fluid volume change. It is ideally suited for drug delivery into small, sensitive and unique fluid spaces such as the cochlea. We characterized the pharmacokinetics of reciprocating drug delivery to the scala tympani within the cochlea by measuring the effects of changes in flow parameters on the distribution of drug throughout the length of the cochlea. Distribution was assessed by monitoring the effects of DNQX, a reversible glutamate receptor blocker, delivered directly to the inner ear of guinea pigs using reciprocating flow profiles. We then modeled the effects of those parameters on distribution using both an iterative curve-fitting approach and a computational fluid dynamic model. Our findings are consistent with the hypothesis that reciprocating delivery distributes the drug into a volume in the base of the cochlea, and suggest that the primary determinant of distribution throughout more distal regions of the cochlea is diffusion. Increases in flow rate distributed the drug into a larger volume that extended more apically. Over short time courses (less than 2h), the apical extension, though small, significantly enhanced apically directed delivery of drug. Over longer time courses (>5h) or greater distances (>3mm), maintenance of drug concentration in the basal scala tympani may prove more advantageous for extending apical delivery than increases in flow rate. These observations demonstrate that this reciprocating technology is capable of providing controlled delivery kinetics to the closed fluid space in the cochlea, and may be suitable for other applications such as localized brain and retinal delivery. Copyright © 2011 Elsevier B.V. All rights reserved.

Kinetics of Reciprocating Drug Delivery to the Inner Ear

PubMed Central

Leary Pararas, Erin E.; Chen, Zhiqiang; Fiering, Jason; Mescher, Mark J.; Kim, Ernest S.; McKenna, Michael J.; Kujawa, Sharon G.; Borenstein, Jeffrey T.; Sewell, William F.

2011-01-01

Reciprocating drug delivery is a means of delivering soluble drugs directly to closed fluid spaces in the body via a single cannula without an accompanying fluid volume change. It is ideally suited for drug delivery into small, sensitive and unique fluid spaces such as the cochlea. We characterized the pharmacokinetics of reciprocating drug delivery to the scala tympani within the cochlea by measuring the effects of changes in flow parameters on the distribution of drug throughout the length of the cochlea. Distribution was assessed by monitoring the effects of DNQX, a reversible glutamate receptor blocker, delivered directly to the inner ear of guinea pigs using reciprocating flow profiles. We then modeled the effects of those parameters on distribution using both an iterative curve-fitting approach and a computational fluid dynamic model. Our findings are consistent with the hypothesis that reciprocating delivery distributes the drug into a volume in the base of the cochlea, and suggest that the primary determinant of distribution throughout more distal regions of the cochlea is diffusion. Increases in flow rate distributed the drug into a larger volume that extended more apically. Over short time courses (less than 2 h), the apical extension, though small, significantly enhanced apically directed delivery of drug. Over longer time courses (>5 h) or greater distances (>3 mm), maintenance of drug concentration in the basal scala tympani may prove more advantageous for extending apical delivery than increases in flow rate. These observations demonstrate that this reciprocating technology is capable of providing controlled delivery kinetics to the closed fluid space in the cochlea, and may be suitable for other applications such as localized brain and retinal delivery. PMID:21385596

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.

An overview of pharmacology and clinical aspects concerning the therapy of cochleo-vestibular syndromes by intratympanic drug delivery

PubMed Central

CHIRTEŞ, FELICIAN; ALBU, SILVIU

2013-01-01

Intratympanic drug delivery refers to drug administration in the middle ear, the main advantage being direct diffusion of substances in the inner ear through the round window membrane with subsequent high intralabiryntine drug concentration and very low systemic side effects. The article is a review of literature concerning the inner ear barrier systems, the physiology of inner ear fluids, intralabirinthine pharmacokinetics and the commonest drugs applied in the middle ear for the treatment of cochleo-vestibular syndromes. PMID:26527944

Electrostatic Self-Assembled Chitosan-Pectin Nano- and Microparticles for Insulin Delivery.

PubMed

Maciel, Vinicius B V; Yoshida, Cristiana M P; Pereira, Susana M S S; Goycoolea, Francisco M; Franco, Telma T

2017-10-12

A polyelectrolyte complex system of chitosan-pectin nano- and microparticles was developed to encapsulate the hormone insulin. The aim of this work was to obtain small particles for oral insulin delivery without chemical crosslinkers based on natural and biodegradable polysaccharides. The nano- and microparticles were developed using chitosans (with different degrees of acetylation: 15.0% and 28.8%) and pectin solutions at various charge ratios (n⁺/n - given by the chitosan/pectin mass ratio) and total charge. Nano- and microparticles were characterized regarding particle size, zeta potential, production yield, encapsulation efficiency, stability in different media, transmission electron microscopy and cytotoxicity assays using Caco-2 cells. The insulin release was evaluated in vitro in simulated gastric and intestinal media. Small-sized particles (~240-~1900 nm) with a maximum production yield of ~34.0% were obtained. The highest encapsulation efficiency (~62.0%) of the system was observed at a charge ratio (n⁺/n - ) 5.00. The system was stable in various media, particularly in simulated gastric fluid (pH 1.2). Transmission electron microscopy (TEM) analysis showed spherical shape particles when insulin was added to the system. In simulated intestinal fluid (pH 6.8), controlled insulin release occurred over 2 h. In vitro tests indicated that the proposed system presents potential as a drug delivery for oral administration of bioactive peptides.

Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil.

PubMed

Ishida, Tatsuhiro; Takanashi, Yoshihiro; Kiwada, Hiroshi

2006-03-01

Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents.

A new approach in gastroretentive drug delivery system using cholestyramine.

PubMed

Umamaheshwari, R B; Jain, Subheet; Jain, N K

2003-01-01

We prepared cellulose acetate butyrate (CAB)-coated cholestyramine microcapsules as a intragastric floating drug delivery system endowed with floating ability due to the carbon dioxide generation when exposed to the gastric fluid. The microcapsules also have a mucoadhesive property. Ion-exchange resin particles can be loaded with bicarbonate followed by acetohydroxamic acid (AHA) and coated with CAB by emulsion solvent evaporation method. The drug concentration was monitored to maintain the floating property and minimum effective concentration. The effect of CAB: drug-resin ratio (2:1, 4:1, 6:1 w/w) on the particle size, floating time, and drug release was determined. Cholestyramine microcapsules were characterized for shape, surface characteristics, and size distribution; cholestyramine/acetohydroxamic acid interactions inside microcapsules were investigated by X-ray diffractometry. The buoyancy time of CAB-coated formulations was better than that of uncoated resin particles. Also, a longer floating time was observed with a higher polymer:drug resin complex ratio (6:1). With increasing coating thickness the particle size was increased but drug release rate was decreased. The drug release rate was higher in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). The in vivo mucoadhesion studies were performed with rhodamine-isothiocyanate (RITC) by fluorescent probe method. The amount of CAB-coated cholestyramine microcapsules that remained in the stomach was slightly lower than that of uncoated resin particles. Cholestyramine microcapsules were distributed throughout the stomach and exhibited prolonged gastric residence via mucoadhesion. These results suggest that CAB-coated microcapsules could be a floating as well as a mucoadhesive drug delivery system. Thus, it has promise in the treatment of Helicobacter pylori.

Apparatus for advancing a wellbore using high power laser energy

DOEpatents

Zediker, Mark S.; Land, Mark S.; Rinzler, Charles C.; Faircloth, Brian O.; Koblick, Yeshaya; Moxley, Joel F.

2014-09-02

Delivering high power laser energy to form a borehole deep into the earth using laser energy. Down hole laser tools, laser systems and laser delivery techniques for advancement, workover and completion activities. A laser bottom hole assembly (LBHA) for the delivery of high power laser energy to the surfaces of a borehole, which assembly may have laser optics, a fluid path for debris removal and a mechanical means to remove earth.

Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

PubMed

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

2015-01-01

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

Use of urea and creatinine levels in vaginal fluid for the diagnosis of preterm premature rupture of membranes and delivery interval after membrane rupture.

PubMed

Gezer, Cenk; Ekin, Atalay; Golbasi, Ceren; Kocahakimoglu, Ceysu; Bozkurt, Umit; Dogan, Askin; Solmaz, Ulaş; Golbasi, Hakan; Taner, Cuneyt Eftal

2017-04-01

To determine whether urea and creatinine measurements in vaginal fluid could be used to diagnose preterm premature rupture of membranes (PPROM) and predict delivery interval after PPROM. A prospective study conducted with 100 pregnant women with PPROM and 100 healthy pregnant women between 24 + 0 and 36 + 6 gestational weeks. All patients underwent sampling for urea and creatinine concentrations in vaginal fluid at the time of admission. Receiver operator curve analysis was used to determine the cutoff values for the presence of PPROM and delivery within 48 h after PPROM. In multivariate logistic regression analysis, vaginal fluid urea and creatinine levels were found to be significant predictors of PPROM (p < 0.001 and p < 0.001, respectively) and delivery within 48 h after PPROM (p = 0.012 and p = 0.017, respectively). The optimal cutoff values for the diagnosis of PPROM were >6.7 mg/dl for urea and >0.12 mg/dl for creatinine. The optimal cutoff values for the detection of delivery within 48 h were >19.4 mg/dl for urea and >0.23 mg/dl for creatinine. Measurement of urea and creatinine levels in vaginal fluid is a rapid and reliable test for diagnosing and also for predicting delivery interval after PPROM.

Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid.

PubMed

Gonzalez, Ana Maria; Leadbeater, Wendy; Podvin, Sonia; Borboa, Alexandra; Burg, Michael; Sawada, Ritsuko; Rayner, James; Sims, Karen; Terasaki, Tetsuya; Johanson, Conrad; Stopa, Edward; Eliceiri, Brian; Baird, Andrew

2010-11-04

Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain. Copyright © 2010 Elsevier B.V. All rights reserved.

Fluid Dynamics Assessment of the VPCAR Water Recovery System in Partial and Microgravity

NASA Technical Reports Server (NTRS)

Niederhaus, Charles; Nahra, Henry; Flynn, Michael

2006-01-01

The Vapor Phase Catalytic Ammonia Removal (VPCAR) system is being developed to recycle water for future NASA Exploration Missions. Testing was recently conducted on NASA s C-9B Reduced Gravity Aircraft to determine the microgravity performance of a key component of the VPCAR water recovery system. Six flights were conducted to evaluate the fluid dynamics of the Wiped-Film Rotating Disk (WFRD) distillation component of the VPCAR system in microgravity, focusing on the water delivery method. The experiments utilized a simplified system to study the process of forming a thin film on a disk similar to that in the evaporator section of VPCAR. Fluid issues are present with the current configuration, and the initial alternative configurations were only partial successful in microgravity operation. The underlying causes of these issues are understood, and new alternatives are being designed to rectify the problems.

Design and Integration of a Scent Delivery System in the Computer Assisted Rehabilitation Environment (CAREN)

DTIC Science & Technology

2013-12-06

Sulfurous Volcano 1643 Burnt Flesh 219 Burning Rubber 1645 Dead Body 243 Diesel Exhaust 1690 Vomit 252 Oily Machinery/Hydraulic Fluid Food 1432...Vehicle 1664 Cumin 1650 Tar Asphalt 1680 Rosemary Focaccia Bread 1680 Car Bomb 1990 Garlic 1905 Turpentine 1992 Mesquite BBQ Scent System

Diagnostic/drug delivery "sense-respond" devices, systems, and uses thereof

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

Polsky, Ronen; Miller, Philip Rocco; Edwards, Thayne L.

The present invention is directed to devices, systems, and methods for detecting and/or monitoring one or more markers in a sample. In particular, such devices integrate a plurality of hollow needles configured to extract or obtain a fluid sample from a subject, as well as transducers to detect a marker of interest.

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

PubMed

Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

2015-11-01

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

LOx breathing system with gas permeable-liquid impermeable heat exchange and delivery hose

DOEpatents

Hall, M.N.

1996-04-30

Life support apparatus is composed of: a garment for completely enclosing a wearer and constructed for preventing passage of gas from the environment surrounding the garment; a portable receptacle holding a quantity of an oxygen-containing fluid in liquid state, the fluid being in a breathable gaseous state when at standard temperature and pressure; a fluid flow member secured within the garment and coupled to the receptacle for conducting the fluid in liquid state from the receptacle to the interior of the garment; and a fluid flow control device connected for causing fluid to flow from the receptacle to the fluid flow member at a rate determined by the breathable air requirement of the wearer, wherein fluid in liquid state is conducted into the interior of the garment at a rate to be vaporized and heated to a breathable temperature by body heat produced by the wearer. 6 figs.

Systems and method for delivering liquified gas to an engine

DOEpatents

Bingham, Dennis N.; Wilding, Bruce M.; O'Brien, James E.; Siahpush, Ali S.; Brown, Kevin B.

2002-01-01

A liquified gas delivery system for a motorized platform includes a holding tank configured to receive liquified gas. A first conduit extends from a vapor holding portion of the tank to a valve device. A second conduit extends from a liquid holding portion of the tank to the valve device. Fluid coupled to the valve device is a vaporizer which is in communication with an engine. The valve device selectively withdraws either liquified gas or liquified gas vapor from the tank depending on the pressure within the vapor holding portion of the tank. Various configurations of the delivery system can be utilized for pressurizing the tank during operation.

Systems for delivering liquified gas to an engine

DOEpatents

Bingham, Dennis N.; Wilding, Bruce M.; O'Brien, James E.; Siahpush, Ali S.; Brown, Kevin B.

2006-05-16

A liquified gas delivery system for a motorized platform includes a holding tank configured to receive liquified gas. A first conduit extends from a vapor holding portion of the tank to a valve device. A second conduit extends from a liquid holding portion of the tank to the valve device. Fluid coupled to the valve device is a vaporizer which is in communication with an engine. The valve device selectively withdraws either liquified gas or liquified gas vapor from the tank depending on the pressure within the vapor holding portion of the tank. Various configurations of the delivery system can be utilized for pressurizing the tank during operation.

Description and operation of Haakon School geothermal heating system

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

Childs, F.W.; Kirol, L.D.; Sanders, R.D.

1997-12-01

Haakon School is located in the city of Philip, near the Badlands National Park in the southwest quadrant of South Dakota. The town overlies the Madison Formation which is a large-area aquifer. The aquifer has a demonstrated capability to produce geothermal water. A system to tap this potential and heat the Haakon School District buildings in Philip has been in operation since November 1980. Five school buildings having a total area of 44,000 ft{sup 2} (4088 ft{sup 2}) are heated with 157{degrees}F (69{degrees}C) water. A single well provides water at a maximum artesian flow of 340 gpm (21.5 L/s), whichmore » more than meets the heat demand of the school buildings. Eight buildings in the Philip business district utilize geothermal fluid discharged from the school for space heating. During the 1980-81 heating season, these buildings obtained 75% to 90% of their heat from geothermal fluid. Peak heat delivery of the system is 5.5 million Btu/h (1.61. MJ/s), with an annual energy delivery of 9.5 billion Btu (10 TJ). The geothermal system has operated nearly problem free with the exception of the equipment to remove Radium-226 from the spent fluid. Barium chloride is added to the water to precipitate sulfates containing the radium. Accumulation of precipitates in piping has caused some operational problems.« less

The wettability and swelling of selected mucoadhesive polymers in simulated saliva and vaginal fluids.

PubMed

Rojewska, M; Olejniczak-Rabinek, M; Bartkowiak, A; Snela, A; Prochaska, K; Lulek, J

2017-08-01

The surface properties play a particularly important role in the mucoadhesive drug delivery systems. In these formulations, the adsorption of polymer matrix to mucous membrane is limited by the wetting and swelling process of the polymer structure. Hence, the performance of mucoadhesive drug delivery systems made of polymeric materials depends on multiple factors, such as contact angle, surface free energy and water absorption rate. The aim of our study was to analyze the effect of model saliva and vaginal fluids on the wetting properties of selected mucoadhesive (Carbopol 974P NF, Noveon AA-1, HEC) and film-forming (Kollidon VA 64) polymers as well as their blends at the weight ratio 1:1 and 1:1:1, prepared in the form of discs. Surface properties of the discs were determined by measurements of advancing contact angle on the surface of polymers and their blends using the sessile drop method. The surface energy was determined by the OWRK method. Additionally, the mass swelling factor and hydration percentage of examined polymers and their blends in simulated biological fluids were evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Simulation model of converging-diverging (CD) nozzle to improve particle delivery system of deoxyribonucleic acid (DNA)

NASA Astrophysics Data System (ADS)

Sumarsono, Danardono A.; Ibrahim, Fera; Santoso, Satria P.; Sari, Gema P.

2018-02-01

Gene gun is a mechanical device which has been used to deliver DNA vaccine into the cells and tissues by increasing the uptake of DNA plasmid so it can generate a high immune response with less amount of DNA. Nozzle is an important part of the gene gun which used to accelerate DNA in particle form with a gas flow to reach adequate momentum to enter the epidermis of human skin and elicit immune response. We developed new designs of nozzle for gene gun to make DNA uptake more efficient in vaccination. We used Computational Fluid Dynamics (CFD) by Autodesk® Simulation 2015 to simulate static fluid pressure and velocity contour of supersonic wave and parametric distance to predict the accuracy of the new nozzle. The result showed that the nozzle could create a shockwave at the distance parametric to the object from 4 to 5 cm using fluid pressure varied between 0.8-1.2 MPa. This is indication a possibility that the DNA particle could penetrate under the mammalian skin. For the future research step, this new nozzle model could be considered for development the main component of the DNA delivery system in vaccination in vivo

Lipid nanoparticles as drug/gene delivery systems to the retina.

PubMed

del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

2013-03-01

This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.

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

Chance, Ronald; Koros, William J.; McCool, Benjamin

The invention provides systems and methods for the delivery of carbon to photoautotrophs. The invention utilizes low energy regeneration of adsorbent for CO.sub.2 capture and provides for effective CO.sub.2 loading into liquids useful for photoautotroph growth and/or production of photosynthetic products, such as biofuels, via photoautotrophic culture media. The inventive system comprises a fluid/membrane/fluid contactor that provides selective transfer of molecular CO.sub.2 via a dense (non-porous) membrane from a carbonate-based CO.sub.2 snipping solution to a culture medium where the CO.sub.2 is consumed by a photoautotroph for the production of biofuels, biofuel precursors or other commercial products.

Transport efficiency in transdermal drug delivery: What is the role of fluid microstructure?

PubMed

Liuzzi, Roberta; Carciati, Antonio; Guido, Stefano; Caserta, Sergio

2016-03-01

Interaction of microstructured fluids with skin is ubiquitous in everyday life, from the use of cosmetics, lotions, and drugs, to personal care with detergents or soaps. The formulation of microstructured fluids is crucial for the control of the transdermal transport. In biomedical applications transdermal delivery is an efficient approach, alternative to traditional routes like oral and parenteral administration, for local release of drugs. Poor skin permeability, mainly due to its outer layer, which acts as the first barrier against the entry of external compounds, greatly limits the applicability of transdermal delivery. In this review, we focus on recent studies on the improvement of skin transport efficiency by using microemulsions (ME). Quantitative techniques, which are able to investigate both skin morphology and penetration processes, are also reviewed. ME are increasingly used as transdermal systems due to their low preparation cost, stability and high bioavailability. ME may act as penetration enhancers for many active principles, but ME microstructure should be chosen appropriately considering several factors such as ratio and type of ingredients and physic-chemical properties of the active components. ME microstructure is strongly affected by the flow conditions applied during processing, or during spreading and rubbing onto skin. Although the role played by ME microstructure has been generally recognized, the skin transport mechanisms associated with different ME microstructures are still to be elucidated and further investigations are required to fully exploit the potential of ME in transdermal delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Term amniotic fluid: an unexploited reserve of mesenchymal stromal cells for reprogramming and potential cell therapy applications.

PubMed

Moraghebi, Roksana; Kirkeby, Agnete; Chaves, Patricia; Rönn, Roger E; Sitnicka, Ewa; Parmar, Malin; Larsson, Marcus; Herbst, Andreas; Woods, Niels-Bjarne

2017-08-25

Mesenchymal stromal cells (MSCs) are currently being evaluated in numerous pre-clinical and clinical cell-based therapy studies. Furthermore, there is an increasing interest in exploring alternative uses of these cells in disease modelling, pharmaceutical screening, and regenerative medicine by applying reprogramming technologies. However, the limited availability of MSCs from various sources restricts their use. Term amniotic fluid has been proposed as an alternative source of MSCs. Previously, only low volumes of term fluid and its cellular constituents have been collected, and current knowledge of the MSCs derived from this fluid is limited. In this study, we collected amniotic fluid at term using a novel collection system and evaluated amniotic fluid MSC content and their characteristics, including their feasibility to undergo cellular reprogramming. Amniotic fluid was collected at term caesarean section deliveries using a closed catheter-based system. Following fluid processing, amniotic fluid was assessed for cellularity, MSC frequency, in-vitro proliferation, surface phenotype, differentiation, and gene expression characteristics. Cells were also reprogrammed to the pluripotent stem cell state and differentiated towards neural and haematopoietic lineages. The average volume of term amniotic fluid collected was approximately 0.4 litres per donor, containing an average of 7 million viable mononuclear cells per litre, and a CFU-F content of 15 per 100,000 MNCs. Expanded CFU-F cultures showed similar surface phenotype, differentiation potential, and gene expression characteristics to MSCs isolated from traditional sources, and showed extensive expansion potential and rapid doubling times. Given the high proliferation rates of these neonatal source cells, we assessed them in a reprogramming application, where the derived induced pluripotent stem cells showed multigerm layer lineage differentiation potential. The potentially large donor base from caesarean section deliveries, the high yield of term amniotic fluid MSCs obtainable, the properties of the MSCs identified, and the suitability of the cells to be reprogrammed into the pluripotent state demonstrated these cells to be a promising and plentiful resource for further evaluation in bio-banking, cell therapy, disease modelling, and regenerative medicine applications.

An elevated amniotic fluid prostaglandin F2α concentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes.

PubMed

Park, Jee Yoon; Romero, Roberto; Lee, JoonHo; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun

2016-01-01

To determine whether an elevated amniotic fluid concentration of prostaglandin F2α (PGF2α) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes. The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (< 35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). PGF2α was measured with a sensitive and specific immunoassay. The amniotic fluid PGF2α concentration was considered elevated when it was above the 95th percentile among pregnant women at 15-36 weeks of gestation who were not in labor (≥170 pg/mL). (1) The prevalence of an elevated amniotic fluid PGF2α concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF2α concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p = 0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p = 0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF2α (p < 0.05 for each); and (3) an elevated amniotic fluid PGF2α concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4-3.1; p = 0.001]. The concentration of PGF2α was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis.

Standard on microbiological management of fluids for hemodialysis and related therapies by the Japanese Society for Dialysis Therapy 2008.

PubMed

Kawanishi, Hideki; Akiba, Takashi; Masakane, Ikuto; Tomo, Tadashi; Mineshima, Michio; Kawasaki, Tadayuki; Hirakata, Hideki; Akizawa, Tadao

2009-04-01

The Committee of Scientific Academy of the Japanese Society for Dialysis Therapy (JSDT) proposes a new standard on microbiological management of fluids for hemodialysis and related therapies. This standard is within the scope of the International Organization for Standardization (ISO), which is currently under revision. This standard is to be applied to the central dialysis fluid delivery systems (CDDS), which are widely used in Japan. In this standard, microbiological qualities for dialysis water and dialysis fluids are clearly defined by endotoxin level and bacterial count. The qualities of dialysis fluids were classified into three levels: standard, ultrapure, and online prepared substitution fluid. In addition, the therapeutic application of each dialysis fluid is clarified. Since high-performance dialyzers are frequently used in Japan, the standard recommends that ultrapure dialysis fluid be used for all dialysis modalities at all dialysis facilities. It also recommends that the dialysis equipment safety management committee at each facility should validate the microbiological qualities of online prepared substitution fluid.

Economic optimization of the energy transport component of a large distributed solar power plant

NASA Technical Reports Server (NTRS)

Turner, R. H.

1976-01-01

A solar thermal power plant with a field of collectors, each locally heating some transport fluid, requires a pipe network system for eventual delivery of energy power generation equipment. For a given collector distribution and pipe network geometry, a technique is herein developed which manipulates basic cost information and physical data in order to design an energy transport system consistent with minimized cost constrained by a calculated technical performance. For a given transport fluid and collector conditions, the method determines the network pipe diameter and pipe thickness distribution and also insulation thickness distribution associated with minimum system cost; these relative distributions are unique. Transport losses, including pump work and heat leak, are calculated operating expenses and impact the total system cost. The minimum cost system is readily selected. The technique is demonstrated on six candidate transport fluids to emphasize which parameters dominate the system cost and to provide basic decision data. Three different power plant output sizes are evaluated in each case to determine severity of diseconomy of scale.

AFM fluid delivery/liquid extraction surface sampling/electrostatic spray cantilever probe

DOEpatents

Van Berkel, Gary J.

2015-06-23

An electrospray system comprises a liquid extraction surface sampling probe. The probe comprises a probe body having a liquid inlet and a liquid outlet, and having a liquid extraction tip. A solvent delivery conduit is provided for receiving solvent liquid from the liquid inlet and delivering the solvent liquid to the liquid extraction tip. An open liquid extraction channel extends across an exterior surface of the probe body from the liquid extraction tip to the liquid outlet. An electrospray emitter tip is in liquid communication with the liquid outlet of the liquid extraction surface sampling probe. A system for analyzing samples, a liquid junction surface sampling system, and a method of analyzing samples are also disclosed.

Automated hybridization/imaging device for fluorescent multiplex DNA sequencing

DOEpatents

Weiss, R.B.; Kimball, A.W.; Gesteland, R.F.; Ferguson, F.M.; Dunn, D.M.; Di Sera, L.J.; Cherry, J.L.

1995-11-28

A method is disclosed for automated multiplex sequencing of DNA with an integrated automated imaging hybridization chamber system. This system comprises an hybridization chamber device for mounting a membrane containing size-fractionated multiplex sequencing reaction products, apparatus for fluid delivery to the chamber device, imaging apparatus for light delivery to the membrane and image recording of fluorescence emanating from the membrane while in the chamber device, and programmable controller apparatus for controlling operation of the system. The multiplex reaction products are hybridized with a probe, the enzyme (such as alkaline phosphatase) is bound to a binding moiety on the probe, and a fluorogenic substrate (such as a benzothiazole derivative) is introduced into the chamber device by the fluid delivery apparatus. The enzyme converts the fluorogenic substrate into a fluorescent product which, when illuminated in the chamber device with a beam of light from the imaging apparatus, excites fluorescence of the fluorescent product to produce a pattern of hybridization. The pattern of hybridization is imaged by a CCD camera component of the imaging apparatus to obtain a series of digital signals. These signals are converted by the controller apparatus into a string of nucleotides corresponding to the nucleotide sequence an automated sequence reader. The method and apparatus are also applicable to other membrane-based applications such as colony and plaque hybridization and Southern, Northern, and Western blots. 9 figs.

Automated hybridization/imaging device for fluorescent multiplex DNA sequencing

DOEpatents

Weiss, Robert B.; Kimball, Alvin W.; Gesteland, Raymond F.; Ferguson, F. Mark; Dunn, Diane M.; Di Sera, Leonard J.; Cherry, Joshua L.

1995-01-01

A method is disclosed for automated multiplex sequencing of DNA with an integrated automated imaging hybridization chamber system. This system comprises an hybridization chamber device for mounting a membrane containing size-fractionated multiplex sequencing reaction products, apparatus for fluid delivery to the chamber device, imaging apparatus for light delivery to the membrane and image recording of fluorescence emanating from the membrane while in the chamber device, and programmable controller apparatus for controlling operation of the system. The multiplex reaction products are hybridized with a probe, then an enzyme (such as alkaline phosphatase) is bound to a binding moiety on the probe, and a fluorogenic substrate (such as a benzothiazole derivative) is introduced into the chamber device by the fluid delivery apparatus. The enzyme converts the fluorogenic substrate into a fluorescent product which, when illuminated in the chamber device with a beam of light from the imaging apparatus, excites fluorescence of the fluorescent product to produce a pattern of hybridization. The pattern of hybridization is imaged by a CCD camera component of the imaging apparatus to obtain a series of digital signals. These signals are converted by the controller apparatus into a string of nucleotides corresponding to the nucleotide sequence an automated sequence reader. The method and apparatus are also applicable to other membrane-based applications such as colony and plaque hybridization and Southern, Northern, and Western blots.

Current HPLC Methods for Assay of Nano Drug Delivery Systems.

PubMed

Tekkeli, Serife Evrim Kepekci; Kiziltas, Mustafa Volkan

2017-01-01

In nano drug formulations the mechanism of release is a critical process to recognize controlled and targeted drug delivery systems. In order to gain high bioavailability and specificity from the drug to reach its therapeutic goal, the active substance must be loaded into the nanoparticles efficiently. Therefore, the amount in biological fluids or tissues and the remaining amount in nano carriers are very important parameters to understand the potential of the nano drug delivery systems. For this aim, suitable and validated quantitation methods are required to determine released drug concentrations from nano pharmaceutical formulations. HPLC (High Performance Liquid Chromatography) is one of the most common techniques used for determination of released drug content out of nano drug formulations, in different physical conditions, over different periods of time. Since there are many types of HPLC methods depending on detector and column types, it is a challenge for the researchers to choose a suitable method that is simple, fast and validated HPLC techniques for their nano drug delivery systems. This review's goal is to compare HPLC methods that are currently used in different nano drug delivery systems in order to provide detailed and useful information for researchers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Recent advancement of gelatin nanoparticles in drug and vaccine delivery.

PubMed

Sahoo, Nityananda; Sahoo, Ranjan Ku; Biswas, Nikhil; Guha, Arijit; Kuotsu, Ketousetuo

2015-11-01

Novel drug delivery system using nanoscale materials with a broad spectrum of applications provides a new therapeutic foundation for technological integration and innovation. Nanoparticles are suitable drug carrier for various routes of administration as well as rapid recognition by the immune system. Gelatin, the biological macromolecule is a versatile drug/vaccine delivery carrier in pharmaceutical field due to its biodegradable, biocompatible, non-antigenicity and low cost with easy availability. The surface of gelatin nanoparticles can be modified with site-specific ligands, cationized with amine derivatives or, coated with polyethyl glycols to achieve targeted and sustained release drug delivery. Compared to other colloidal carriers, gelatin nanoparticles are better stable in biological fluids to provide the desired controlled and sustained release of entrapped drug molecules. The current review highlights the different formulation aspects of gelatin nanoparticles which affect the particle characteristics like zeta potential, polydispersity index, entrapment efficacy and drug release properties. It has also given emphasis on the major applications of gelatin nanoparticles in drug and vaccine delivery, gene delivery to target tissues and nutraceutical delivery for improving the poor bioavailabity of bioactive phytonutrients. Copyright © 2015 Elsevier B.V. All rights reserved.

Flutter instability of cantilevered carbon nanotubes caused by magnetic fluid flow subjected to a longitudinal magnetic field

NASA Astrophysics Data System (ADS)

Sadeghi-Goughari, Moslem; Jeon, Soo; Kwon, Hyock-Ju

2018-04-01

CNT (Carbon nanotube)-based fluidic systems hold a great potential for emerging medical applications such as drug delivery for cancer therapy. CNTs can be used to deliver anticancer drugs into a target site under a magnetic field guidance. One of the critical issues in designing such systems is how to avoid the vibration induced by the fluid flow, which is undesirable and may even promote the structural instability. The main objective of the present research is to develop a fluid structure interaction (FSI) model to investigate the flutter instability of a cantilevered CNT induced by a magnetic fluid flow under a longitudinal magnetic field. The CNT is assumed to be embedded in a viscoelastic matrix to consider the effect of biological medium around it. To obtain a dynamical model for the system, the Navier-Stokes theory of magnetic-fluid flow is coupled to the Euler-Bernoulli beam model for CNT. The small size effects of the magnetic fluid and CNT are considered through the small scale parameters including Knudsen number (Kn) and the nonlocal parameter. Then, the extended Galerkin's method is applied to solve the FSI governing equations, and to derive the stability diagrams of the system. Results show how the magnetic properties of the fluid flow have an effect on improving the stability of the cantilevered CNT by increasing the flutter velocity.

Characterization and Analyses of Valves, Feed Lines and Tanks used in Propellant Delivery Systems at NASA SSC

NASA Technical Reports Server (NTRS)

Ryan, Harry M.; Coote, David J.; Ahuja, Vineet; Hosangadi, Ashvin

2006-01-01

Accurate modeling of liquid rocket engine test processes involves assessing critical fluid mechanic and heat and mass transfer mechanisms within a cryogenic environment, and accurately modeling fluid properties such as vapor pressure and liquid and gas densities as a function of pressure and temperature. The Engineering and Science Directorate at the NASA John C. Stennis Space Center has developed and implemented such analytic models and analysis processes that have been used over a broad range of thermodynamic systems and resulted in substantial improvements in rocket propulsion testing services. In this paper, we offer an overview of the analyses techniques used to simulate pressurization and propellant fluid systems associated with the test stands at the NASA John C. Stennis Space Center. More specifically, examples of the global performance (one-dimensional) of a propellant system are provided as predicted using the Rocket Propulsion Test Analysis (RPTA) model. Computational fluid dynamic (CFD) analyses utilizing multi-element, unstructured, moving grid capability of complex cryogenic feed ducts, transient valve operation, and pressurization and mixing in propellant tanks are provided as well.

Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study

NASA Astrophysics Data System (ADS)

Chen, Fei-Yan; Yi, Jing-Wei; Gu, Zhe-Jia; Tang, Bin-Bing; Li, Jian-Qi; Li, Li; Kulkarni, Padmakar; Liu, Li; Mason, Ralph P.; Tang, Qun

2016-03-01

On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors.On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors. Electronic supplementary information (ESI) available: HRTEM image and electron diffraction pattern of individual GdAsOx NPs, cell viability measurements after 48 and 72 hours of incubation, body weight change curves, hematology curves, liver function curves, and renal function curves. See DOI: 10.1039/c6nr00536e

Cylinders vs. Spheres: Biofluid Shear Thinning in Driven Nanoparticle Transport

PubMed Central

Cribb, Jeremy A.; Meehan, Timothy D.; Shah, Sheel M.; Skinner, Kwan; Superfine, Richard

2011-01-01

Increasingly, the research community applies magnetophoresis to micro and nanoscale particles for drug delivery applications and the nanoscale rheological characterization of complex biological materials. Of particular interest is the design and transport of these magnetic particles through entangled polymeric fluids commonly found in biological systems. We report the magnetophoretic transport of spherical and rod-shaped particles through viscoelastic, entangled solutions using lambda-phage DNA (λ-DNA) as a model system. In order to understand and predict the observed phenomena, we fully characterize three fundamental components: the magnetic field and field gradient, the shape and magnetic properties of the probe particles, and the macroscopic rheology of the solution. Particle velocities obtained in Newtonian solutions correspond to macroscale rheology, with forces calculated via Stokes Law. In λ-DNA solutions, nanorod velocities are 100 times larger than predicted by measured zero-shear viscosity. These results are consistent with particles experiencing transport through a shear thinning fluid, indicating magnetically driven transport in shear thinning may be especially effective and favor narrow diameter, high aspect ratio particles. A complete framework for designing single-particle magnetic-based delivery systems results when we combine a quantified magnetic system with qualified particles embedded in a characterized viscoelastic medium. PMID:20571853

Lox breathing system with gas permeable-liquid impermeable heat exchange and delivery hose

DOEpatents

Hall, Mark N.

1996-01-01

Life support apparatus composed of: a garment (2): for completely enclosing a wearer and constructed for preventing passage of gas from the environment surrounding the garment (2); a portable receptacle (6) holding a quantity of an oxygen-containing fluid in liquid state, the fluid being in a breathable gaseous; state when at standard temperature and pressure; a fluid flow member (16) secured within the garment (2) and coupled to the receptacle (6) for conducting the fluid in liquid state from the receptacle (6) to the interior of the garment (2); and a fluid flow control device (14) connected for causing fluid to flow from the receptacle (6) to the fluid flow member (16) at a rate determined by the breathable air requirement of the wearer, wherein fluid in liquid state is conducted into the interior of the garment (2) at a rate to be vaporized and heated to a breathable temperature by body heat produced by the wearer.

Methods For Delivering Liquified Gas To An Engine

DOEpatents

Bingham, Dennis N.; Wilding, Bruce M.; O'Brien, James E.; Siahpush, Ali S.; Brown, Kevin B.

2003-09-16

A liquified gas delivery system for a motorized platform includes a holding tank configured to receive liquified gas. A first conduit extends from a vapor holding portion of the tank to a valve device. A second conduit extends from a liquid holding portion of the tank to the valve device. Fluid coupled to the valve device is a vaporizer which is in communication with an engine. The valve device selectively withdraws either liquified gas or liquified gas vapor from the tank depending on the pressure within the vapor holding portion of the tank. Various configurations of the delivery system can be utilized for pressurizing the tank during operation.

Methods For Delivering Liquified Gas To An Engine

DOEpatents

Bingham, Dennis N.; Wilding, Bruce M.; O'Brien, James E.; Siahpush, Ali S.; Brown, Kevin B.

2005-10-11

A liquified gas delivery system for a motorized platform includes a holding tank configured to receive liquified gas. A first conduit extends from a vapor holding portion of the tank to a valve device. A second conduit extends from a liquid holding portion of the tank to the valve device. Fluid coupled to the valve device is a vaporizer which is in communication with an engine. The valve device selectively withdraws either liquified gas or liquified gas vapor from the tank depending on the pressure within the vapor holding portion of the tank. Various configurations of the delivery system can be utilized for pressurizing the tank during operation.

Fuels and Lubricants Influence on Turbine Engine Design and Performance

DTIC Science & Technology

1974-08-01

Temperatures, Mission A. 30 16. Misrion A Interceptor ECS SchemaLiu. 32 17. GEl4/FLiTE-2A Fuel Delivery System Schematic. 34 18. GE14 /FLITE-2A Oil Sump...Layout Drawing. 36 19. G0E4/FL,I’LE-2A LubriaLiui SysLem Schematic. 37 20. GEl4/FLITE-2A Fluid Power System Schematic. 41 21. GE14 /FLITE-2A Fluid Syqtem...Schematic. 1 35 63. GEI4/FI,ITE-2B ThermaL Profiles, MIL-L-27502. 140 64. GE14 /FLIT.-2B Thermal Profiles, 500’ F E’ster. 141 .ix 7 LIST OF ILUWSTRAT LON

Exosomes: Nanoparticulate tools for RNA interference and drug delivery.

PubMed

Shahabipour, Fahimeh; Barati, Nastaran; Johnston, Thomas P; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein

2017-07-01

Exosomes are naturally occurring extracellular vesicles released by most mammalian cells in all body fluids. Exosomes are known as key mediators in cell-cell communication and facilitate the transfer of genetic and biochemical information between distant cells. Structurally, exosomes are composed of lipids, proteins, and also several types of RNAs which enable these vesicles to serve as important disease biomarkers. Moreover, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Recently, increasing attention has been focused on exosomes for the delivery of drugs, including therapeutic recombinant proteins, to various target tissues. Exosomes are also promising vehicles for the delivery of microRNAs and small interfering RNAs, which is usually hampered by rapid degradation of these RNAs, as well as inefficient tissue specificity of currently available delivery strategies. This review highlights the most recent accomplishments and trends in the use of exosomes for the delivery of drugs and therapeutic RNA molecules. © 2017 Wiley Periodicals, Inc.

Surfactants: their critical role in enhancing drug delivery to the lungs.

PubMed

Morales, Javier O; Peters, Jay I; Williams, Robert O

2011-05-01

For local lung conditions and diseases, pulmonary drug delivery has been widely used for more than 50 years now. A more recent trend involves the pulmonary route as a systemic drug-delivery target. Advantages such as avoidance of the gastrointestinal environment, different enzyme content compared with the intestine, and avoidance of first-pass metabolism make the lung an alternative route for the systemic delivery of actives. However, the lung offers barriers to absorption such as a surfactant layer, epithelial surface lining fluid, epithelial monolayer, interstitium and basement membrane, and capillary endothelium. Many delivery strategies have been developed in order to overcome these limitations. The use of surfactants is one of these approaches and their role in enhancing pulmonary drug delivery is reviewed in this article. A systematic review of the literature relating to the effect of surfactants on formulations for pulmonary delivery was conducted. Specifically, research reporting enhancement of in vivo performance was focused on. The effect of the addition of surfactants such as phospholipids, bile salts, non-ionic, fatty acids, and liposomes as phospholipid-containing carriers on the enhancement of therapeutic outcomes of drugs for pulmonary delivery was compiled. The main use attributed to surfactants in pulmonary drug delivery is as absorption enhancers by mechanisms of action not yet fully understood. Furthermore, surfactants have been used to improve the delivery of inhaled drugs in various additional strategies discussed herein.

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

Zediker, Mark S.; Land, Mark S.; Rinzler, Charles C.

A system, apparatus and methods for delivering high power laser energy to perform laser operations in oil fields and to form a borehole deep into the earth using laser energy. A laser downhole assembly for the delivery of high power laser energy to surfaces and areas in a borehole, which assembly may have laser optics and a fluid path.

Microbial diversity within basement fluids of the sediment-buried Juan de Fuca Ridge flank

PubMed Central

Jungbluth, Sean P; Grote, Jana; Lin, Huei-Ting; Cowen, James P; Rappé, Michael S

2013-01-01

Despite its immense size, logistical and methodological constraints have largely limited microbiological investigations of the subseafloor basement biosphere. In this study, a unique sampling system was used to collect fluids from the subseafloor basaltic crust via a Circulation Obviation Retrofit Kit (CORK) observatory at Integrated Ocean Drilling Program borehole 1301A, located at a depth of 2667 m in the Pacific Ocean on the eastern flank of the Juan de Fuca Ridge. Here, a fluid delivery line directly accesses a 3.5 million years old basalt-hosted basement aquifer, overlaid by 262 m of sediment, which serves as a barrier to direct exchange with bottom seawater. At an average of 1.2 × 104 cells ml−1, microorganisms in borehole fluids were nearly an order of magnitude less abundant than in surrounding bottom seawater. Ribosomal RNA genes were characterized from basement fluids, providing the first snapshots of microbial community structure using a high-integrity fluid delivery line. Interestingly, microbial communities retrieved from different CORKs (1026B and 1301A) nearly a decade apart shared major community members, consistent with hydrogeological connectivity. However, over three sampling years, the dominant gene clone lineage changed from relatives of Candidatus Desulforudis audaxviator within the bacterial phylum Firmicutes in 2008 to the Miscellaneous Crenarchaeotic Group in 2009 and a lineage within the JTB35 group of Gammaproteobacteria in 2010, and statistically significant variation in microbial community structure was observed. The enumeration of different phylogenetic groups of cells within borehole 1301A fluids supported our observation that the deep subsurface microbial community was temporally dynamic. PMID:22791235

Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology.

PubMed

Meng, Jianing; Agrahari, Vivek; Youm, Ibrahima

2017-03-01

At present, brain tumor is among the most challenging diseases to treat and the therapy is limited by the lack of effective methods to deliver anticancer agents across the blood-brain barrier (BBB). BBB is a selective barrier that separates the circulating blood from the brain extracellular fluid. In its neuroprotective function, BBB prevents the entry of toxins, as well as most of anticancer agents and is the main impediment for brain targeted drug delivery approaches. Nanotechnology-based delivery systems provide an attractive strategy to cross the BBB and reach the central nervous system (CNS). The incorporation of anticancer agents in various nanovehicles facilitates their delivery across the BBB. Moreover, a more powerful tool in brain tumor therapy has relied surface modifications of nanovehicles with specific ligands that can promote their passage through the BBB and favor the accumulation of the drug in CNS tumors. This review describes the physiological and anatomical features of the brain tumor and the BBB, and summarizes the recent advanced approaches to deliver anticancer drugs into brain tumor using nanobiotechnology-based drug carrier systems. The role of specific ligands in the design of functionalized nanovehicles for targeted delivery to brain tumor is reviewed. The current trends and future approaches in the CNS delivery of therapeutic molecules to tumors are also discussed.

Tissue Bioeffects during Ultrasound-mediated Drug Delivery

NASA Astrophysics Data System (ADS)

Sutton, Jonathan

Ultrasound has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles, or ultrasound contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi, or direct drugs to optimal locations for delivery. These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery. This dissertation addresses a fundamental hypothesis in biomedical ultrasound: ultrasound-mediated drug delivery is capable of increasing the penetration of drugs across different physiologic barriers within the cardiovascular system, such as the vascular endothelium, blood clots, and smooth muscle cells.

Systems for delivering liquified natural gas to an engine

DOEpatents

Bingham, Dennis N.; Wilding, Bruce M.; O'Brien, James E.; Siahpush, Ali S.; Brown, Kevin B.

2000-01-01

A fuel delivery system includes a fuel tank configured to receive liquid natural gas. A first conduit extends from a vapor holding portion of the fuel tank to an economizer valve. A second conduit extends from a liquid holding portion of the fuel tank to the economizer valve. Fluid coupled to the economizer valve is a vaporizer which is heated by coolant from the engine and is positioned below the fuel tank. The economizer valve selectively withdraws either liquid natural gas or vaporized natural gas from the fuel tank depending on the pressure within the vapor holding portion of the fuel tank. A delivery conduit extends from the vaporizer to the engine. A return conduit having a check valve formed therein extends from the delivery conduit to the vapor holding portion of the fuel tank for pressurizing the fuel tank.

Vapor feed direct methanol fuel cells with passive thermal-fluids management system

NASA Astrophysics Data System (ADS)

Guo, Zhen; Faghri, Amir

The present paper describes a novel technology that can be used to manage methanol and water in miniature direct methanol fuel cells (DMFCs) without the need for a complex micro-fluidics subsystem. At the core of this new technology is a unique passive fuel delivery system that allows for fuel delivery at an adjustable rate from a reservoir to the anode. Furthermore, the fuel cell is designed for both passive water management and effective carbon dioxide removal. The innovative thermal management mechanism is the key for effective operation of the fuel cell system. The vapor feed DMFC reached a power density of 16.5 mW cm -2 at current density of 60 mA cm -2. A series of fuel cell prototypes in the 0.5 W range have been successfully developed. The prototypes have demonstrated long-term stable operation, easy fuel delivery control and are scalable to larger power systems. A two-cell stack has successfully operated for 6 months with negligible degradation.

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

NASA Astrophysics Data System (ADS)

Zhang, Yan; Lin, Xia; Du, Xuli; Geng, Sicong; Li, Hongren; Sun, Hong; Tang, Xing; Xiao, Wei

2015-02-01

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the p Ka of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

Medication and volume delivery by gravity-driven micro-drip intravenous infusion: potential variations during "wide-open" flow.

PubMed

Pierce, Eric T; Kumar, Vikram; Zheng, Hui; Peterfreund, Robert A

2013-03-01

Gravity-driven micro-drip infusion sets allow control of medication dose delivery by adjusting drops per minute. When the roller clamp is fully open, flow in the drip chamber can be a continuous fluid column rather than discrete, countable, drops. We hypothesized that during this "wide-open" state, drug delivery becomes dependent on factors extrinsic to the micro-drip set and is therefore difficult to predict. We conducted laboratory experiments to characterize volume delivery under various clinically relevant conditions of wide-open flow in an in vitro laboratory model. A micro-drip infusion set, plugged into a bag of normal saline, was connected to a high-flow stopcock at the distal end. Vertically oriented IV catheters (gauges 14-22) were connected to the stopcock. The fluid meniscus height in the bag was fixed (60-120 cm) above the outflow point. The roller clamp on the infusion set was in fully open position for all experiments resulting in a continuous column of fluid in the drip chamber. Fluid volume delivered in 1 minute was measured 4 times with each condition. To model resistive effects of carrier flow, volumetric infusion pumps were used to deliver various flow rates of normal saline through a carrier IV set into which a micro-drip infusion was "piggybacked." We also compared delivery by micro-drip infusion sets from 3 manufacturers. The volume of fluid delivered by gravity-driven infusion under wide-open conditions (continuous fluid column in drip chamber) varied 2.9-fold (95% confidence interval, 2.84-2.96) depending on catheter size and fluid column height. Total model resistance of the micro-drip with stopcock and catheter varied with flow rate. Volume delivered by the piggybacked micro-drip decreased up to 29.7% ± 0.8% (mean ± SE) as the carrier flow increased from 0 to 1998 mL/min. Delivery characteristics of the micro-drip infusion sets from 3 different manufacturers were similar. Laboratory simulation of clinical situations with gravity-driven micro-drip infusion sets under wide-open flow conditions revealed that infusion rate (drug and/or volume delivery) can vary widely depending on extrinsic factors including catheter size, fluid column height, and carrier flow. The variable resistance implies nonlaminar flow in the micro-drip model that cannot be easily predicted mathematically. These findings support the use of mechanical pumps instead of gravity-driven micro-drips to enhance the precision and safety of IV infusions, especially for vasoactive drugs.

Revolutionary Impact of Nanodrug Delivery on Neuroscience

PubMed Central

Khanbabaie, Reza; Jahanshahi, Mohsen

2012-01-01

Brain research is the most expanding interdisciplinary research that is using the state of the art techniques to overcome limitations in order to conduct more accurate and effective experiments. Drug delivery to the target site in the central nervous system (CNS) is one of the most difficult steps in neuroscience researches and therapies. Taking advantage of the nanoscale structure of neural cells (both neurons and glia); nanodrug delivery (second generation of biotechnological products) has a potential revolutionary impact into the basic understanding, visualization and therapeutic applications of neuroscience. Current review article firstly provides an overview of preparation and characterization, purification and separation, loading and delivering of nanodrugs. Different types of nanoparticle bioproducts and a number of methods for their fabrication and delivery systems including (carbon) nanotubes are explained. In the second part, neuroscience and nervous system drugs are deeply investigated. Different mechanisms in which nanoparticles enhance the uptake and clearance of molecules form cerebrospinal fluid (CSF) are discussed. The focus is on nanodrugs that are being used or have potential to improve neural researches, diagnosis and therapy of neurodegenerative disorders. PMID:23730260

Treatment of PPROM with anhydramnion in humans: first experience with different amniotic fluid substitutes for continuous amnioinfusion through a subcutaneously implanted port system.

PubMed

Tchirikov, Michael; Bapayeva, Gauri; Zhumadilov, Zhaxybay Sh; Dridi, Yasmina; Harnisch, Ralf; Herrmann, Angelika

2013-11-01

This study aims to treat patients with preterm premature rupture of the membranes (PPROM) and anhydramnion using continuous amnioinfusion through a subcutaneously implanted port system. An amniotic fluid replacement port system was implanted in seven patients with PPROM and anhydramnion starting at the 20th week of gestation (range, 14-26 weeks) for long-term amnioinfusion. Saline solutions (2 L/day; Jonosteril(®), Sterofundin(®), isotonic NaCl 0.9% solution, lactated Ringer's solution) and a hypotonic aqueous composition with reduced chloride content similar to the electrolyte concentration of human amniotic fluid were used for the continuous amnioinfusion. The mean duration of the PPROM delivery interval continued for 49 days (range, 9-69 days), with 3 weeks of amnioinfusion via the port system (range, 4-49). The newborns showed no signs of lung hypoplasia. Long-term lavage of the amniotic cavity via a subcutaneously implanted port system in patients with PPROM and anhydramnion may help prolong the pregnancy and avoid fetal lung hypoplasia. A hypotonic aqueous composition with reduced chloride content similar to human amniotic fluid can be safely used for amnioinfusion. Prospective randomized studies are ongoing.

The new standard of fluids for hemodialysis in Japan.

PubMed

Kawanishi, Hideki; Masakane, Ikuto; Tomo, Tadashi

2009-01-01

The standard of fluids for hemodialysis is being evaluated by the International Organization for Standardization (ISO), and will be decided within a few years. In 2008, the Japanese Society for Dialysis Therapy (JSDT) proposed the standard of fluids for hemodialysis by taking the draft ISO standard into consideration and the circumstances in Japan. It was characteristically a standard for Japan, where the central dialysis fluid delivery system (CDDS) is routinely used. In addition, the therapeutic application of each dialysis fluid is clarified. Since high-performance dialyzers are frequently employed in Japan, the standard recommends that ultrapure dialysis fluid be used for all dialysis modalities at all dialysis facilities. It also recommends that the dialysis equipment safety management committee at each facility validate the microbiological qualities of online-prepared substitution fluid, making the responsibility of the dialysis facility clear. This standard is more rigid than those of other countries, and is expected to contribute to improvements in the survival outcome of dialysis patients. (c) 2009 S. Karger AG, Basel.

Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir

PubMed Central

Malik, Nadia Shamshad; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-01-01

To explore the potential role of polymers in the development of drug-delivery systems, this study investigated the use of β-cyclodextrin (β-CD), carboxymethyl cellulose (CMC), acrylic acid (AA) and N’ N’-methylenebis-acrylamide (MBA) in the synthesis of hydrogels for controlled drug delivery of acyclovir (ACV). Different proportions of β-CD, CMC, AA and MBA were blended with each other to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy (FTIR) revealed successful grafting of components into the polymeric network. Thermal and morphological characterization confirmed the formation of thermodynamically stable hydrogels having porous structure. The pH-responsive behaviour of hydrogels has been documented by swelling dynamics and drug release behaviour in simulated gastrointestinal fluids. Drug release kinetics revealed controlled release behaviour of the antiviral drug acyclovir in developed polymeric network. Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels can be used as promising candidates for the design and development of controlled drug-delivery systems. PMID:28245257

A COMPREHENSIVE INSIGHT ON OCULAR PHARMACOKINETICS

PubMed Central

Agrahari, Vibhuti; Mandal, Abhirup; Agrahari, Vivek; Trinh, Hoang My; Joseph, Mary; Ray, Animikh; Hadji, Hicheme; Mitra, Ranjana; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment model of ocular drug delivery has been developed for describing the absorption, distribution and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems and routes of administration are discussed including factors affecting intraocular bioavailability. Factors such as pre-corneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, drug metabolism renders ocular delivery challenging and elaborated in this manuscript. Several compartment models are discussed those are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations. PMID:27798766

Assay of 6-gingerol in CO2 supercritical fluid extracts of ginger and evaluation of its sustained release from a transdermal delivery system across rat skin.

PubMed

Chen, Yan; Zhang, Cuiping; Zhang, Mei; Fu, Xiaobing

2014-07-01

Ginger has been widely used as healthy food condiment as well as traditional Chinese medicine since antiquity. Multiple potentials of ginger for treatment of various ailments have been revealed. However, the biological half-life of 6-gingerol (a principal pungent ingredient of ginger) is only 7.23 minutes while taken orally. Delivery of ginger compositions by routes other than oral have scarcely been reported. Therefore, we studied a noninvasive transdermal drug delivery system (TDDS) of ginger to bypass hepatic first pass metabolism, avoid gastrointestinal degradation and achieve long persistent release of effective compositions. After establishment of a HPLC analysis method of 6-gingerol, assays of 6-gingerol were performed to compare two kinds of ginger extracts. Then, the characteristics of transdermal delivery of 6-gingerol in TDDS were exhibited. The results showed that the contents of 6-gingerol in two kinds of ginger extracts were significantly different. The maximal delivery percentage of 6-gingerol across rat skin at 20 h was more than 40% in different TDDS formulations. TDDS may provide long-lasting delivery of ginger compounds.

HESTIA Commodities Exchange Pallet and Sounding Rocket Test Stand

NASA Technical Reports Server (NTRS)

Chaparro, Javier

2013-01-01

During my Spring 2016 internship, my two major contributions were the design of the Commodities Exchange Pallet and the design of a test stand for a 100 pounds-thrust sounding rocket. The Commodities Exchange Pallet is a prototype developed for the Human Exploration Spacecraft Testbed for Integration and Advancement (HESTIA) program. Under the HESTIA initiative the Commodities Exchange Pallet was developed as a method for demonstrating multi-system integration thru the transportation of In-Situ Resource Utilization produced oxygen and water to a human habitat. Ultimately, this prototype's performance will allow for future evaluation of integration, which may lead to the development of a flight capable pallet for future deep-space exploration missions. For HESTIA, my main task was to design the Commodities Exchange Pallet system to be used for completing an integration demonstration. Under the guidance of my mentor, I designed, both, the structural frame and fluid delivery system for the commodities pallet. The fluid delivery system includes a liquid-oxygen to gaseous-oxygen system, a water delivery system, and a carbon-dioxide compressors system. The structural frame is designed to meet safety and transportation requirements, as well as the ability to interface with the ER division's Portable Utility Pallet. The commodities pallet structure also includes independent instrumentation oxygen/water panels for operation and system monitoring. My major accomplishments for the commodities exchange pallet were the completion of the fluid delivery systems and the structural frame designs. In addition, parts selection was completed in order to expedite construction of the prototype, scheduled to begin in May of 2016. Once the commodities pallet is assembled and tested it is expected to complete a fully integrated transfer demonstration with the ISRU unit and the Environmental Control and Life Support System test chamber in September of 2016. In addition to the development of the Commodities Exchange Pallet, I also assisted in preparation for testing the upper stage of a sounding rocket developed as a Center Innovation Fund project. The main objective of this project is to demonstrate the integration between a propulsion system and a solid oxide fuel cell (SOFC). The upper stage and SOFC are scheduled to complete an integrated test in August of 2016. As part of preparation for scheduled testing, I was responsible for designing the upper stage's test stand/support structure and main engine plume deflector to be used during hot-fire testing (fig. 3). The structural components of the test stand need to meet safety requirements for operation of the propulsion system, which consist of a 100 pounds-thrust main engine and two 15 pounds-thrust reaction control thrusters. My main accomplishment for this project was the completion of the design and the parts selection for construction of the structure, scheduled to begin late April of 2016.

Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems.

PubMed

Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I

2018-05-17

Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing. Copyright © 2018 Elsevier B.V. All rights reserved.

Drug-targeting methodologies with applications: A review

PubMed Central

Kleinstreuer, Clement; Feng, Yu; Childress, Emily

2014-01-01

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

Cryogenic fluid management for low-g transfer

NASA Technical Reports Server (NTRS)

Frank, D. J.; Jaekle, D. E., Jr.

1986-01-01

An account is given of design and operations criteria pertaining to low-g environment systems for the collection and delivery of liquid cryogens to a supply tank drain inlet in orbit. Analyses must assess the draining efficiencies of such devices, because the minimization of supply tank residual contents is of the essence. Settling accelerations, passive expulsion, and positive expulsion methods of fluid control have all been successfully demonstrated in orbit. Attention is given to the unique advantages and disadvantages of each method in view of different sets of requirements.

MAST Propellant and Delivery System Design Methods

NASA Technical Reports Server (NTRS)

Nadeem, Uzair; Mc Cleskey, Carey M.

2015-01-01

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

Toward oral delivery of biopharmaceuticals: an assessment of the gastrointestinal stability of 17 peptide drugs.

PubMed

Wang, Jie; Yadav, Vipul; Smart, Alice L; Tajiri, Shinichiro; Basit, Abdul W

2015-03-02

A major barrier to successful oral delivery of peptide and protein molecules is their inherent instability in the lumen of the gastrointestinal tract. The aim of this study was to determine the stability of 17 disparate peptide drugs (insulin, calcitonin, glucagon, secretin, somatostatin, desmopressin, oxytocin, [Arg(8)]-vasopressin, octreotide, ciclosporin, leuprolide, nafarelin, buserelin, histrelin, [d-Ser](4)-gonadorelin, deslorelin, and goserelin) in gastric and small intestinal fluids from both humans and pigs, and in simulated gastric and intestinal fluids. In human gastric fluid, the larger peptides including somatostatin, calcitonin, secretin, glucagon, and insulin were metabolized rapidly, while the smaller peptides showed good stability. In human small intestinal fluid, however, both small and large peptides degraded rapidly with the exception of the cyclic peptide ciclosporin and the disulfide-bridge containing peptides octreotide and desmopressin, which showed good stability. The stability of peptides in both simulated gastric fluid and pig gastric fluid correlated well with stability in human gastric fluid. However, it was not possible to establish such a correlation with the small intestinal fluids because of the rapid rate of peptide degradation. This work has identified the molecular features in the structure of a wide range of peptides that influence their stability in the environment of the gastrointestinal tract, which in turn will allow for better selection of peptide candidates for oral delivery.

Non-invasive imaging of barriers to drug delivery in tumors.

PubMed

Hassid, Yaron; Eyal, Erez; Margalit, Raanan; Furman-Haran, Edna; Degani, Hadassa

2008-08-01

Solid tumors often develop high interstitial fluid pressure (IFP) as a result of increased water leakage and impaired lymphatic drainage, as well as changes in the extracellular matrix composition and elasticity. This high fluid pressure forms a barrier to drug delivery and hence, resistance to therapy. We have developed techniques based on contrast enhanced magnetic resonance imaging for mapping in tumors the vascular and transport parameters determining the delivery efficiency of blood borne substances. Sequential images are recorded during continuous infusion of a Gd-based contrast agent and analyzed according to a new physiological model, yielding maps of microvascular transfer constants, as well as outward convective interstitial transfer constants and steady state interstitial contrast agent concentrations both reflecting IFP distribution. We further demonstrated in non small cell human lung cancer xenografts the capability of our techniques to monitor in vivo collagenase induced increase in contrast agent delivery as a result of decreased IFP. These techniques can be applied to test drugs that affect angiogenesis and modulate interstitial fluid pressure and has the potential to be extended to cancer patients for assessing resistance to drug delivery.

Non-Invasive Imaging of Barriers to Drug Delivery in Tumors

PubMed Central

Hassid, Yaron; Eyal, Erez; Margalit, Raanan; Furman-Haran, Edna; Degani, Hadassa

2011-01-01

Solid tumors often develop high interstitial fluid pressure (IFP) as a result of increased water leakage and impaired lymphatic drainage, as well as changes in the extracellular matrix composition and elasticity. This high fluid pressure forms a barrier to drug delivery and hence, resistance to therapy. We have developed techniques based on contrast enhanced magnetic resonance imaging for mapping in tumors the vascular and transport parameters determining the delivery efficiency of blood borne substances. Sequential images are recorded during continuous infusion of a Gd-based contrast agent and analyzed according to a new physiological model, yielding maps of microvascular transfer constants, as well as outward convective interstitial transfer constants and steady state interstitial contrast agent concentrations both reflecting IFP distribution. We further demonstrated in non small cell human lung cancer xenografts the capability of our techniques to monitor in vivo collagenase induced increase in contrast agent delivery as a result of decreased IFP. These techniques can be applied to test drugs that affect angiogenesis and modulate interstitial fluid pressure and has the potential to be extended to cancer patients for assessing resistance to drug delivery. PMID:18638494

Method and Apparatus for Forming Nanodroplets

NASA Technical Reports Server (NTRS)

Ackley, Donald; Forster, Anita

2011-01-01

This innovation uses partially miscible fluids to form nano- and microdroplets in a microfluidic droplet generator system. Droplet generators fabricated in PDMS (polydimethylsiloxane) are currently being used to fabricate engineered nanoparticles and microparticles. These droplet generators were first demonstrated in a T-junction configuration, followed by a cross-flow configuration. All of these generating devices have used immiscible fluids, such as oil and water. This immiscible fluid system can produce mono-dispersed distributions of droplets and articles with sizes ranging from a few hundred nanometers to a few hundred microns. For applications such as drug delivery, the ability to encapsulate aqueous solutions of drugs within particles formed from the droplets is desirable. Of particular interest are non-polar solvents that can dissolve lipids for the formation of liposomes in the droplet generators. Such fluids include ether, cyclohexane, butanol, and ethyl acetate. Ethyl acetate is of particular interest for two reasons. It is relatively nontoxic and it is formed from ether and acetic acid, and maybe broken down into its constituents at relatively low concentrations.

Accuracy and consistency of drop delivery in infusion pumps.

PubMed

Yau, K I; Miyasaka, K

1990-04-01

Advances in intensive care medicine has made us more depend on infusion pumps to deliver accurate amounts of fluids to sick newborns, children and adults. When infusing rapid-acting critical drugs to patients, it is important not only to deliver accurate fluid-volume amounts over a specified time, but also to deliver the fluid at a constant rate with minimal fluctuation. The accuracy of drop delivery in four infusion pumps (IVAC 530, IVAC 560, IMED 922 and IMED 960) at different infusion rates were examined in a laboratory setting by using a photoelectric sensor and a computer. When it was not in its cassette-filling period, the IMED 960 was the most accurate at delivering fluid-drops, with a coefficient of variance (CV) of less than 10% at each flow rate. Yet, like other piston-cylinder cassette pumps, its cassette filling time and stabilizing period after cassette filling were longer at lower flow rates. Both the IVAC 530 and the IMED 922 delivered fluids irregularly with large coefficients of variance (CVs). IVAC 560 had the best results for consistency of drop-delivery over a 4-hour period.

Piloted rich-catalytic lean-burn hybrid combustor

DOEpatents

Newburry, Donald Maurice

2002-01-01

A catalytic combustor assembly which includes, an air source, a fuel delivery means, a catalytic reactor assembly, a mixing chamber, and a means for igniting a fuel/air mixture. The catalytic reactor assembly is in fluid communication with the air source and fuel delivery means and has a fuel/air plenum which is coated with a catalytic material. The fuel/air plenum has cooling air conduits passing therethrough which have an upstream end. The upstream end of the cooling conduits is in fluid communication with the air source but not the fuel delivery means.

Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.

PubMed

Grabovac, Vjera; Föger, Florian; Bernkop-Schnürch, Andreas

2008-02-04

The aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo. The patch system consisted of a mucoadhesive layer, a water insoluble backing layer made of ethylcellulose and an enteric coating made of Eudragit. Drug release studies were performed in media mimicking stomach and intestinal fluids. For in vivo studies patch systems were administered orally to conscious non-diabetic rats. Orally administered insulin in aqueous solution was used as control. After the oral administration of the patch systems a decrease of glucose and increase of insulin blood levels were measured. The mucoadhesive layer, exhibiting a diameter of 2.5mm and a weight of 5mg, comprised polycarbophil-cysteine conjugate (49%), bovine insulin (26%), gluthatione (5%) and mannitol (20%). 74.8+/-4.8% of insulin was released from the delivery system over 6h. Six hours after administration of the patch system mean maximum decrease of blood glucose level of 31.6% of the initial value could be observed. Maximum insulin concentration in blood was 11.3+/-6.2ng/ml and was reached 6h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%. The results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.

Effect of tumor shape, size, and tissue transport properties on drug delivery to solid tumors

PubMed Central

2014-01-01

Background The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, drug extravasation from microvessels or to lymphatic vessels. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to investigate the effect of tumor shape and size on drug delivery to solid tumor. Methods The advanced mathematical model used in our previous work is further developed by adding solute transport equation to the governing equations. After applying appropriate boundary and initial conditions on tumor and surrounding tissue geometry, the element-based finite volume method is used for solving governing equations of drug delivery in solid tumor. Also, the effects of size and shape of tumor and some of tissue transport parameters such as effective pressure and hydraulic conductivity on interstitial fluid flow and drug delivery are investigated. Results Sensitivity analysis shows that drug delivery in prolate shape is significantly better than other tumor shapes. Considering size effect, increasing tumor size decreases drug concentration in interstitial fluid. This study shows that dependency of drug concentration in interstitial fluid to osmotic and intravascular pressure is negligible. Conclusions This study shows that among diffusion and convection mechanisms of drug transport, diffusion is dominant in most different tumor shapes and sizes. In tumors in which the convection has considerable effect, the drug concentration is larger than that of other tumors at the same time post injection. PMID:24987457

Multi-tube thermal fuse for nozzle protection from a flame holding or flashback event

DOEpatents

Lacy, Benjamin Paul; Davis, Jr., Lewis Berkley; Johnson, Thomas Edward; York, William David

2012-07-03

A protection system for a pre-mixing apparatus for a turbine engine, includes: a main body having an inlet portion, an outlet portion and an exterior wall that collectively establish a fuel delivery plenum; and a plurality of fuel mixing tubes that extend through at least a portion of the fuel delivery plenum, each of the plurality of fuel mixing tubes including at least one fuel feed opening fluidly connected to the fuel delivery plenum; at least one thermal fuse disposed on an exterior surface of at least one tube, the at least one thermal fuse including a material that will melt upon ignition of fuel within the at least one tube and cause a diversion of fuel from the fuel feed opening to at least one bypass opening. A method and a turbine engine in accordance with the protection system are also provided.

The effect of type and volume of fluid hydration on labor duration of nulliparous women: a randomized controlled trial.

PubMed

Garmi, Gali; Zuarez-Easton, Sivan; Zafran, Noah; Ohel, Iris; Berkovich, Ilanit; Salim, Raed

2017-06-01

Type and volume of fluid administered for intrapartum maintenance had been reported to differently affect labor length, delivery mode, and cord artery pH and glucose level. We aimed to compare the effect of three different fluid regimens on labor duration. In a randomized trial, healthy nulliparous in labor were randomized into one of three intravenous fluid regimens: group 1, the reference group, lactated Ringer's solution infused at a rate of 125 mL/h; group 2, lactated Ringer's solution infused at a rate of 250 mL/h; group 3, 0.9% saline solution boosted with 5% glucose, infused at a rate of 125 mL/h. The primary outcome was labor length from enrollment until delivery. Between December 2010 and July 2015, 300 women were randomized to one of the three groups. Demographic and baseline obstetric characteristics were comparable between the groups. There was no significant difference in the time from enrollment to delivery (p = 0.62). Furthermore, there were no significant differences in second stage duration (p = 0.73), mode of delivery (p = 0.21), cord artery pH and glucose level between the groups. Increasing the intravenous volume of lactated Ringer's solution or substituting to fluid containing 5% glucose solution does not affect labor length. ClinicalTrials.gov, http://www.clinicaltrials.gov , NCT01242293.

EUS-guided drainage of pancreatic fluid collections using a novel lumen-apposing metal stent on an electrocautery-enhanced delivery system: a large retrospective study (with video).

PubMed

Rinninella, Emanuele; Kunda, Rastislav; Dollhopf, Markus; Sanchez-Yague, Andres; Will, Uwe; Tarantino, Ilaria; Gornals Soler, Joan; Ullrich, Sebastian; Meining, Alexander; Esteban, Josè Miguel; Enz, Thomas; Vanbiervliet, Geoffroy; Vleggaar, Frank; Attili, Fabia; Larghi, Alberto

2015-12-01

A lumen-apposing, self-expanding metal stent incorporated in an electrocautery-enhanced delivery system for EUS-guided drainage of pancreatic fluid collections (PFCs) recently has become available. The aim of this study was to analyze the safety and clinical effectiveness of this newly developed device in this clinical setting. This was a retrospective analysis of all consecutive patients with PFCs who underwent EUS-guided drainage using the study device in 13 European centers. Ninety-three patients with PFCs (80% with complex collections) underwent drainage using the study device. Penetration of the PFC was accomplished directly with the study device in 74.2% of patients, and successful stent placement was accomplished in all but 1 patient, mostly without fluoroscopic assistance. Direct endoscopic necrosectomy (DEN) was carried out in 31 of 52 cases (59.6%) of walled-off necrosis and in 2 of 4 cases (50%) of acute peripancreatic fluid collection. Complete resolution of the PFC was obtained in 86 cases (92.5%), with no recurrence during follow-up. Treatment failure occurred in 6 patients because of persistent infection requiring surgery (n = 3), perforation and massive bleeding caused by the nasocystic drainage catheter (NCDC) (n = 2), and the need for a larger opening to extract large necrotic tissue pieces (n = 1). Major adverse events occurred in 5 patients (perforation and massive bleeding caused by the NCDC in 2 patients, 1 pneumoperitoneum and 1 stent dislodgement during DEN, and 1 postdrainage infection) and were mostly not related to the drainage procedure. EUS-guided drainage with the electrocautery-enhanced delivery system is a safe, easy to perform, and a highly effective minimally invasive treatment modality for PFCs. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Fabrication Methods and Performance of Low-Permeability Microfluidic Components for a Miniaturized Wearable Drug Delivery System

PubMed Central

Mescher, Mark J.; Swan, Erin E. Leary; Fiering, Jason; Holmboe, Maria E.; Sewell, William F.; Kujawa, Sharon G.; McKenna, Michael J.; Borenstein, Jeffrey T.

2010-01-01

In this paper, we describe low-permeability components of a microfluidic drug delivery system fabricated with versatile micromilling and lamination techniques. The fabrication process uses laminate sheets which are machined using XY milling tables commonly used in the printed-circuit industry. This adaptable platform for polymer microfluidics readily accommodates integration with silicon-based sensors, printed-circuit, and surface-mount technologies. We have used these methods to build components used in a wearable liquid-drug delivery system for in vivo studies. The design, fabrication, and performance of membrane-based fluidic capacitors and manual screw valves provide detailed examples of the capability and limitations of the fabrication method. We demonstrate fluidic capacitances ranging from 0.015 to 0.15 μL/kPa, screw valves with on/off flow ratios greater than 38 000, and a 45× reduction in the aqueous fluid loss rate to the ambient due to permeation through a silicone diaphragm layer. PMID:20852729

Analysis of the Postoperative Periarticular Environment and Influence on Sustained Drug Delivery from a Gel Formulation.

PubMed

Svirskis, Darren; Martis, Waldron; Bhusal, Prabhat; Sharma, Manisha; Stowers, Renus; Young, Simon W

2018-05-16

Regional intraarticular delivery of local anaesthetics is effective in treating postoperative pain following total knee or hip replacement. Recent research efforts have been only partially successful in achieving sustained release of the analgesic agent, in part due to limited understanding of the biological environment into which these formulations are administered. This study aimed to detail the composition and properties of postoperative periarticular fluid (PO-PAF). PO-PAF was collected from 8 patients and the composition and physicochemical properties determined. A number of components were identified which are lacking from phosphate buffered saline (PBS) or other synthetic media. The differences in composition led to variation in the physicochemical properties of PO-PAF compared with PBS. Notably, significantly lower surface tension (p<0.05) and higher buffer capacity (p<0.05) were observed in the biological fluid. We demonstrated the solubility of lidocaine is almost double in PO-PAF compared to PBS (p<0.05) and that lidocaine release from a poloxamer gelling system occurred faster into PO-PAF under both sink and non-sink conditions. Collectively, these data indicate PBS is inappropriate for the in-vitro evaluation of intraarticular drug delivery systems. The presented data describes PO-PAF and will support the future development of biorelevant media to ultimately improve in-vivo in-vitro correlation. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Applicability of an ultrasonic nebulization system for the airways delivery of beclomethasone dipropionate in a murine model of asthma.

PubMed

Hrvacić, Boska; Bosnjak, Berislav; Tudja, Marijan; Mesić, Milan; Merćep, Mladen

2006-08-01

We have assessed the use of an ultrasonic nebulization system (UNS), composed of ultrasonic nebulizer and diffusion dryer filled with charcoal, for the effective delivery of beclomethasone to the airways in a murine asthma model. Solution of beclomethasone in ethanol was aerosolized using an ultrasonic nebulizer. Passage of the aerosol through a drying column containing charcoal and deionizer produced dry beclomethasone particles. Particles were delivered to BALB/c mice placed in a whole-body exposition chamber 1 h before intranasal challenge with ovalbumine. Efficacy of beclomethasone delivery was evaluated by examining bronchoalveolar lavage fluid (BALF) cytology. Effect of three UNS system parameters on aerosol particle size was investigated. The critical parameter affecting the size of dry particles was beclomethasone concentration in aerosolized solution and solution flow rate while power level of ultrasonic nebulizer generator had no effect. Administration of beclomethasone at calculated dose of 150 microg/kg to mice significantly decreased total cell number and relative eosinophil number in BALF. The UNS system produces a monodisperse aerosol that can be used for inhalative delivery of poorly water soluble substances to experimental animals. The UNS system minimizes formulation requirements and allows rapid and relatively simple efficacy and toxicity testing in animals.

Electronic nicotine delivery systems: is there a need for regulation?

PubMed

Trtchounian, Anna; Talbot, Prue

2011-01-01

Electronic nicotine delivery systems (ENDS) purport to deliver nicotine to the lungs of smokers. Five brands of ENDS were evaluated for design features, accuracy and clarity of labelling and quality of instruction manuals and associated print material supplied with products or on manufacturers' websites. ENDS were purchased from online vendors and analysed for various parameters. While the basic design of ENDS was similar across brands, specific design features varied significantly. Fluid contained in cartridge reservoirs readily leaked out of most brands, and it was difficult to assemble or disassemble ENDS without touching nicotine-containing fluid. Two brands had designs that helped lessen this problem. Labelling of cartridges was very poor; labelling of some cartridge wrappers was better than labelling of cartridges. In general, packs of replacement cartridges were better labelled than the wrappers or cartridges, but most packs lacked cartridge content and warning information, and sometimes packs had confusing information. Used cartridges contained fluid, and disposal of nicotine-containing cartridges was not adequately addressed on websites or in manuals. Orders were sometimes filled incorrectly, and safety features did not always function properly. Print and internet material often contained information or made claims for which there is currently no scientific support. Design flaws, lack of adequate labelling and concerns about quality control and health issues indicate that regulators should consider removing ENDS from the market until their safety can be adequately evaluated.

Evolutionary space station fluids management strategies

NASA Technical Reports Server (NTRS)

1989-01-01

Results are summarized for an 11-month study to define fluid storage and handling strategies and requirements for various specific mission case studies and their associated design impacts on the Space Station. There are a variety of fluid users which require a variety of fluids and use rates. Also, the cryogenic propellants required for NASA's STV, Planetary, and Code Z missions are enormous. The storage methods must accommodate fluids ranging from a high pressure gas or supercritical state fluid to a sub-cooled liquid (and superfluid helium). These requirements begin in the year 1994, reach a maximum of nearly 1800 metric tons in the year 2004, and trail off to the year 2018, as currently planned. It is conceivable that the cryogenic propellant needs for the STV and/or Lunar mission models will be met by LTCSF LH2/LO2 tanksets attached to the SS truss structure. Concepts and corresponding transfer and delivery operations have been presented for STV propellant provisioning from the SS. A growth orbit maneuvering vehicle (OMV) and associated servicing capability will be required to move tanksets from delivery launch vehicles to the SS or co-orbiting platforms. Also, appropriate changes to the software used for OMV operation are necessary to allow for the combined operation of the growth OMV. To support fluid management activities at the Space Station for the experimental payloads and propellant provisioning, there must be truss structure space allocated for fluid carriers and propellant tanksets, and substantial beam strengthening may be required. The Station must have two Mobile Remote Manipulator Systems (MRMS) and the growth OMV propellant handling operations for the STV at the SS. Propellant needs for the Planetary Initiatives and Code Z mission models will most likely be provided by co-orbiting propellant platform(s). Space Station impacts for Code Z mission fluid management activities will be minimal.

Decoupled 1D/3D analysis of a hydraulic valve

NASA Astrophysics Data System (ADS)

Mehring, Carsten; Zopeya, Ashok; Latham, Matt; Ihde, Thomas; Massie, Dan

2014-10-01

Analysis approaches during product development of fluid valves and other aircraft fluid delivery components vary greatly depending on the development stage. Traditionally, empirical or simplistic one-dimensional tools are being deployed during preliminary design, whereas detailed analysis such as CFD (Computational Fluid Dynamics) tools are used to refine a selected design during the detailed design stage. In recent years, combined 1D/3D co-simulation has been deployed specifically for system level simulations requiring an increased level of analysis detail for one or more components. The present paper presents a decoupled 1D/3D analysis approach where 3D CFD analysis results are utilized to enhance the fidelity of a dynamic 1D modelin context of an aircraft fuel valve.

Intrapartum and perinatal results associated with different degrees of staining of meconium stained amniotic fluid.

PubMed

Rodríguez Fernández, Vanesa; Ramón Y Cajal, Carlos Nicolás López; Ortiz, Elena Marín; Naveira, Emilio Couceiro

2018-05-01

To determine the intrapartum and perinatal results associated with different degrees of staining of meconium stained amniotic fluid (MSAF). In a retrospective cohort study of all singleton deliveries over a period of one year (2015) in a tertiary hospital, we compared different degrees of MSAF (yellow, green and thick) to clear amniotic fluids, and analysed in each group maternal, intrapartum and neonatal variables as well as umbilical cord blood gas analysis. Of the 3590 deliveries included, 503 (14%) had MSAF. The incidence of MSAF rises with gestational age at delivery, reaching 20.7% in gestations above 41 weeks compared to 4.3% below 37 weeks. As the amniotic fluid staining progresses we found a higher proportion of intrapartum fevers (p < 0.001), pathological fetal heart rate patterns (p < 0.05), operative vaginal deliveries and cesarean sections (p < 0.001), as well as the need for advanced neonatal resuscitation (p < 0.001). There was also a correlation between MSAF and low Apgar scores at five minutes (p < 0.001) and fetal-neonatal mortality (p < 0.001) but there was not a higher proportion of neonatal intensive care admissions (p > 0.05). We have observed a similar distribution of umbilical artery pH ranges in all groups (p > 0.05). MSAF was associated with an increase in the rate of pathological fetal heart rate patterns, intrapartum fevers, operative vaginal and cesarean section deliveries, need for neonatal resuscitation, low Apgar scores and higher fetal-neonatal mortality. Moreover, we found that the risks increase as the staining and consistency of the amniotic fluid evolves so it should alert the obstetrician and paediatrician to the potential adverse outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2014-09-01

our animal vendor, Charles River Laboratories (CRL), to adopt their intrathecal catheterization service for this purpose. Cannulated animals from CRL...pilot “idea” study. Thus, both experimental approaches, catheterization did not allow us to obtain statistically significant therapeutic efficacy...fluid, which will help developing new approaches for delivery of therapies, in particular biopharmaceuticals, to the central nervous system and

MANUAL: ALTERNATIVE METHODS FOR FLUID DELIVERY AND RECOVERY

EPA Science Inventory

Controlling subsurface fluids is among the highest priorities in rnanaging sites with in situ contamination. Some applications direct fluid movement continually inward towards the site, whereas others attempt to recover contaminants and, ultimately, close the site. Both these...

Vernix caseosa peritonitis after vaginal delivery.

PubMed

Sadath, Shameema A; Abo Diba, Fathiya I; Nayak, Surendra; Shamali, Iman Al; Diejomaoh, Michael F

2013-01-01

Vernix caseosa peritonitis (VCP) is a very unusual complication caused by inflammatory response to amniotic fluid spilled into the maternal peritoneal cavity. Twenty-seven cases have been reported, and all occurred after cesarean section. We present a case of VCP following vaginal delivery; this may be the first case reported after vaginal delivery. Mrs. A, 28 years old, gravida 3, para 2, with one previous cesarean section, was admitted at 41 weeks gestation in active labor. Vacuum extraction was performed to deliver a healthy male baby, 4.410 kg, Apgar scores 7, 8. She developed fever, acute abdominal pain, and distension about 3 hours after delivery. A diagnosis of acute abdomen was made. Laparotomy was performed and it revealed neither uterine scar rupture nor other surgical emergencies, but 500 mL of turbid fluid and some cheesy material on the serosal surface of all viscera. Biopsies were taken. She had a course of antibiotics and her recovery was complete. Histology of the peritoneal fluid and tissue biopsy resulted in a diagnosis of VCP. Clinical diagnosis of peritonitis due to vernix caseosa should be considered in patients presenting postpartum with an acute abdomen after vaginal delivery.

Packaged peristaltic micropump for controlled drug delivery application

NASA Astrophysics Data System (ADS)

Vinayakumar, K. B.; Nadiger, Girish; R. Shetty, Vikas; Dinesh, N. S.; Nayak, M. M.; Rajanna, K.

2017-01-01

Micropump technology has evolved significantly in the last two decades and is finding a variety of applications ranging from μTAS (micro Total Analysis System) to drug delivery. However, the application area of the micropump is limited owing to: simple pumping mechanism, ease of handling, controlled (microliter to milliliter) delivery, continuous delivery, and accuracy in flow rate. Here, the author presents the design, development, characterization, and precision flow controlling of a DC-motor driven peristaltic pump for controlled drug delivery application. All the micropump components were fabricated using the conventional fabrication technique. The volume flow variation of the pump has been characterized for different viscous fluids. The change in volume flow due to change in back pressure has been presented in detail. The fail-safe mode operation of the pump has been tested and leak rate was measured (˜0.14% leak for an inlet pressure of 140 kPa) for different inlet pressures. The precision volume flow of the pump has been achieved by measuring the pinch cam position and load current. The accuracy in the volume flow has been measured after 300 rotations. Finally, the complete system has been integrated with the necessary electronics and an android application has been developed for the self-administration of bolus and basal delivery of insulin.

Lysimeter apparatus

DOEpatents

Clark, Don T.; Erickson, Eugene E.; Casper, William L.; Everett, David M.; Hubbell, Joel M.; Sisson, James B.

2005-09-06

A suction lysimeter for sampling subsurface liquids includes a lysimeter casing having a drive portion, a reservoir portion, and a tip portion, the tip portion including a membrane through which subsurface liquids may be sampled; a fluid conduit coupled in fluid flowing relation relative to the membrane, and which in operation facilitates the delivery of the sampled subsurface liquids from the membrane to the reservoir portion; and a plurality of tubes coupled in fluid flowing relation relative to the reservoir portion, the tubes in operation facilitating delivery of the sampled subsurface liquids from the reservoir portion for testing. A method of sampling subsurface liquids comprises using this lysimeter.

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.

PubMed

Plog, Benjamin A; Nedergaard, Maiken

2018-01-24

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.

Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.

PubMed

Elsayed, Amani; Al-Remawi, Mayyas; Qinna, Nidal; Farouk, Asim; Al-Sou'od, Khaldoun A; Badwan, Adnan A

2011-09-01

The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.

The availability of diltiazem: a study on the sorption by intravenous delivery systems and on the stability of the drug.

PubMed

De Vroe, C; De Muynck, C; Remon, J P; Scheldewaert, R; Colardyn, F

1989-04-01

The stability and the sorption by intravenous delivery systems of the calcium antagonist diltiazem dissolved into either 5% dextrose or 0.9% sodium chloride solutions have been investigated, under conditions simulating current clinical practice. Static experiments showed an excellent stability and no sorption after 48 h. Dynamic experiments, at a perfusion rate of 20 mg h-1, showed no sorption of the drug by infusion fluid containers, burettes or administration sets. For end-line filters a temporary decrease of the recovered amount of diltiazem was observed but only with the 0.9% NaCl solution. It is concluded that the stability and the sorption of diltiazem offers no problem with regard to clinical efficacy.

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.

Strategies to improve drug delivery across the blood-brain barrier.

PubMed

de Boer, Albertus G; Gaillard, Pieter J

2007-01-01

The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.

Assessment of fetal inflammatory syndrome by "classical" markers in the management of preterm labor: a possible lesson from metabolomics and system biology.

PubMed

Ferrazzi, Enrico; Muggiasca, Maria Luisa; Fabbri, Elisa; Fontana, Paola; Castoldi, Francesco; Lista, Gianluca; Primerano, Liviana; Livio, Stefania; Di Francesco, Stefania

2012-10-01

There exists a huge gap between protocols issued by scientific bodies and evidence derived by system biology studies on the multifactorial origin of threatened preterm delivery and their different associations with neonatal outcome. The objective of this prospective study was the analysis obstetrical and neonatal outcome in a cohort of pregnant patients treated for the risk of preterm delivery according to maternal and fetal assessment determined by amniotic fluid samples. Methods. Threatened preterm delivery and premature rupture of membranes between 24 + 1 and 32 + 6 weeks of gestation were treated by prolonged tocolytic regimens and if necessary by antibiotics for maternal infections when intra-amniotic inflammation (IAI) was excluded on the basis of negative white blood cell count in the amniotic fluid, or opposite, by delivery after a course of betamethasone and 48 hours maintenance tocolysis. Twenty-three cases were compared with 22 historical controls treated by the same teams according to the 48 hours treat and wait criteria. In addition to this, cases with normal and abnormal amniotic fluid white blood cell were compared. Results. Maternal and fetal conditions at admission were not significantly different between the study and control cohort for all maternal and fetal variables. Clinical indices were significantly improved as regard to latency from admission to delivery, number of newborns admitted to neonatal intensive care unit and length of stay in neonatal intensive care unit. Not any perinatal death or sepsis occurred in the study cohort. Overall, improved neonatal outcomes were observed in the study cohort. Composite major neonatal eventful outcomes occurred in 26% of cases vs. 50% in controls. The limited number of cases was not powered enough to reach a statistical significance for these variables. Continued tocolysis on demand and full regimen of mono or combined antibiotic regimen for maternal infection achieved significantly longer delay between admission to delivery with improved in neonatal outcome in cases negative for IAI: only 2 of 14 newborns suffered of major neonatal complications vs. 4 of 9 newborns delivered for IAI. Conclusions. Fetuses without IAI can be treated conservatively and their stay in utero prolonged without harm. However, we confirmed that when IAI is already active in utero a worse neonatal outcome is already partly predetermined. These positive findings must be interpreted with cautions given the limited number of cases considered by this study.

Delivery of therapeutics for deep-seated ocular conditions - status quo.

PubMed

Nguyen, Hubert; Eng, Shawn; Ngo, Thanh; Dass, Crispin R

2018-04-19

There is a need for research into designing effective pharmaceutical systems for delivering therapeutic drugs to the posterior of the eye for glaucoma-related pathology, macular degeneration, diabetic retinopathy, macular oedema, retinitis and choroiditis. Conventionally, eye drops have been extensively utilised for topical drug delivery to the anterior segment of the eye, but are less effective for delivery of therapeutics to the back of the eye due to significant barriers hampering drug penetration into the target intraocular tissue. This review explores some of the current and novel delivery systems employed to deliver therapeutics to the back of the eye such as those using liposomes, ocular implants, in situ gels, and nanoparticles, and how they can overcome some of these limitations. Issues such as blinking, precorneal fluid drainage, tear dilution and turnover, conjunctiva and nasal drug absorption, the corneal epithelium, vitreous drug clearance, and the blood-ocular barriers are reviewed and discussed. Further studies are needed to address their shortcomings such as drug compatibility and stability, economic viability and patient compliance. © 2018 Royal Pharmaceutical Society.

An oral colon-targeting controlled release system based on resistant starch acetate: synthetization, characterization, and preparation of film-coating pellets.

PubMed

Pu, Huayin; Chen, Ling; Li, Xiaoxi; Xie, Fengwei; Yu, Long; Li, Lin

2011-05-25

An oral colon-targeting controlled release system based on resistant starch acetate (RSA) as a film-coating material was developed. The RSA was successfully synthesized, and its digestion resistibility could be improved by increasing the degree of substitution (DS), which was favorable for the colon-targeting purpose. As a delivery carrier material, the characteristics of RSA were investigated by polarized light microscopy, FTIR spectroscopy, and X-ray diffraction. The results revealed a decrease of the crystallinity of RSA and a change of its crystalline structure from B + V hydrid type to V type. To evaluate the colon-targeting release performance, the RSA film-coated pellets loaded with different bioactive components were prepared by extrusion-spheronization and then by fluid bed coating. The effects of the DS, plasticizer content, and coating thickness of the RSA film and those of the content and molecular weight of the loaded bioactive component on the colon-targeting release performance of the resulting delivery system were investigated. By adjusting the DS, the coating thickness, and the plasticizer content of the RSA film, either the pellets loaded with a small molecular bioactive component such as 5-aminosalicylic acid or those with a macromolecular bioactive peptide or protein such as bovine serum albumin, hepatocyte growth-promoting factor, or insulin showed a desirable colon-targeting release performance. The release percentage was less than 12% in simulated upper gastrointestinal tract and went up to 70% over a period of 40 h in simulated colonic fluid. This suggests that the delivery system based on RSA film has an excellent colon-targeting release performance and the universality for a wide range of bioactive components.

Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.

PubMed

Caccavo, D; Barba, A A; d'Amore, M; De Piano, R; Lamberti, G; Rossi, A; Colombo, P

2017-12-01

The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake

PubMed Central

Ensign, Laura M.; Hoen, Timothy; Maisel, Katharina; Cone, Richard; Hanes, Justin

2013-01-01

Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and muco-inert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanparticles (CP), reached the vaginal epithelial surface in vivo in mice. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that drugs or MPP in isotonic formulations failed to reach efficiently. However, hypotonic formulations caused unencapsulated “free” drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for localized sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. In contrast, as we previously demonstrated, hypotonic delivery of drug via MPP led to better long-term retention and protection in the vagina. Importantly, we demonstrate that slightly hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. Hypotonic formulations for vaginal drug delivery via MPP may significantly improve prevention and treatment of reproductive tract diseases and disorders. PMID:23769419

Formulation development and in-vitro/in-vivo correlation for a novel Sterculia gum-based oral colon-targeted drug delivery system of azathioprine.

PubMed

Nath, Bipul; Nath, Lila Kanta

2013-11-01

The present study was aimed at designing a microflora triggered colon-targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to target azathioprine (AZA) in the colon for the treatment of IBD with reduced systemic toxicity. The microflora degradation study of gum was investigated in rat cecal medium. The polysaccharide tablet was coated to different film thicknesses with blends of chitosan/Eudragit RLPO and over coated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid (SGF) (pH 1.2), simulated intestinal fluid (SIF) (pH 6.8) and simulated colonic fluid (SCF) (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudragit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that, the optimized MCDDS was fitted well into first order model and apparent lag time was found to be 6 h, followed by Higuchi spherical matrix release. The degradation of chitosan was the rate-limiting factor for drug release in the colon. In-vivo study in rabbit shows delayed T(max), prolonged absorption time, decreased C(max) and absorption rate constant (Ka) indicating reduced systemic toxicity of the drug as compared to other dosage forms.

A completely automated flow, heat-capacity, calorimeter for use at high temperatures and pressures

NASA Astrophysics Data System (ADS)

Rogers, P. S. Z.; Sandarusi, Jamal

1990-11-01

An automated, flow calorimeter has been constructed to measure the isobaric heat capacities of concentrated, aqueous electrolyte solutions using a differential calorimetry technique. The calorimeter is capable of operation to 700 K and 40 MPa with a measurement accuracy of 0.03% relative to the heat capacity of the pure reference fluid (water). A novel design encloses the calorimeter within a double set of separately controlled, copper, adiabatic shields that minimize calorimeter heat losses and precisely control the temperature of the inlet fluids. A multistage preheat train, used to efficiently heat the flowing fluid, includes a counter-current heat exchanger for the inlet and outlet fluid streams in tandem with two calorimeter preheaters. Complete system automation is accomplished with a distributed control scheme using multiple processors, allowing the major control tasks of calorimeter operation and control, data logging and display, and pump control to be performed simultaneously. A sophisticated pumping strategy for the two separate syringe pumps allows continuous fluid delivery. This automation system enables the calorimeter to operate unattended except for the reloading of sample fluids. In addition, automation has allowed the development and implementation of an improved heat loss calibration method that provides calorimeter calibration with absolute accuracy comparable to the overall measurement precision, even for very concentrated solutions.

Sildenafil Citrate Therapy for Oligohydramnios: A Randomized Controlled Trial.

PubMed

Maher, Mohammad Ahmed; Sayyed, Tarek Mohammad; Elkhouly, Nabih

2017-04-01

To compare sildenafil plus hydration with hydration alone in improving the amniotic fluid index and neonatal outcomes in pregnancies complicated by idiopathic oligohydramnios ( amniotic fluid index less than 5 cm without underlying maternal or fetal causes and with normal fetal growth). This was an open-label randomized trial for women carrying singleton pregnancies at 30 weeks of gestation or more with idiopathic oligohydramnios detected during routine ultrasonogram. Women received either oral sildenafil citrate (25 mg every 8 hours) plus intravenous infusion of 2 L isotonic solution or fluids only until delivery. The primary study outcome was the amniotic fluid volume at 6 weeks of follow-up or the final volume before delivery, whichever occurred first. Secondary outcomes were duration of pregnancy prolongation, mode of delivery, and select neonatal outcomes. The study was powered to detect a 45% difference between groups, so, at an α level of 0.05 and 80% power, a sample size of 167 women was required. From February 24, 2015, through April 2016, 196 women were screened and 184 were randomized. Follow-up was completed in 166 (90%): 82 in the sildenafil group and 84 in the hydration group. Baseline characteristics were similar between groups. The amniotic fluid volume was higher in the sildenafil group at the final assessment (11.5 compared with 5.4 cm, P=.02). The sildenafil group delivered later (38.3 compared with 36.0 weeks of gestation, P=.001), had a lower rate of cesarean delivery (28% compared with 73%), and their neonates were less likely to be admitted to the neonatal intensive care unit (11% compared with 41%, P=.001). Sildenafil citrate increases amniotic fluid volume in pregnancies complicated by oligohydramnios. ClinicalTrials.gov, www.clinicaltrials.gov, NCT02372487.

Thermally developed peristaltic propulsion of magnetic solid particles in biorheological fluids

NASA Astrophysics Data System (ADS)

Bhatti, M. M.; Zeeshan, A.; Tripathi, D.; Ellahi, R.

2018-04-01

In this article, effects of heat and mass transfer on MHD peristaltic motion of solid particles in a dusty fluid are investigated. The effects of nonlinear thermal radiation and Hall current are also taken into account. The relevant flow analysis is modelled for fluid phase and dust phase in wave frame by means of Casson fluid model. Computation of solutions is presented for velocity profile, temperature profile and concentration profile. The effects of all the physical parameters such as particle volume fraction, Hartmann number, Hall Effect, Prandtl number, Eckert number, Schmidt number and Soret number are discussed mathematically and graphically. It is noted that the influence of magnetic field and particle volume fraction opposes the flow. Also, the impact of particle volume fraction is quite opposite on temperature and concentration profile. This model is applicable in smart drug delivery systems and bacteria movement in urine flow through the ureter.

Disregarded Effect of Biological Fluids in siRNA Delivery: Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles.

PubMed

Dakwar, George R; Braeckmans, Kevin; Demeester, Joseph; Ceelen, Wim; De Smedt, Stefaan C; Remaut, Katrien

2015-11-04

Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the clinic. While numerous successful in vitro siRNA delivery stories exist in reduced-protein conditions, most studies so far overlook the influence of the biological fluids present in the in vivo environment. In this study, we compared the transfection efficiency of liposomal formulations in Opti-MEM (low protein content, routinely used for in vitro screening) and human undiluted ascites fluid obtained from a peritoneal carcinomatosis patient (high protein content, representing the in vivo situation). In Opti-MEM, all formulations are biologically active. In ascites fluid, however, the biological activity of all lipoplexes is lost except for lipofectamine RNAiMAX. The drop in transfection efficiency was not correlated to the physicochemical properties of the nanoparticles, such as premature siRNA release and aggregation of the nanoparticles in the human ascites fluid. Remarkably, however, all of the formulations except for lipofectamine RNAiMAX lost their ability to be taken up by cells following incubation in ascites fluid. To take into account the possible effects of a protein corona formed around the nanoparticles, we recommend always using undiluted biological fluids for the in vitro optimization of nanosized siRNA formulations next to conventional screening in low-protein content media. This should tighten the gap between in vitro and in vivo performance of nanoparticles and ensure the optimal selection of nanoparticles for further in vivo studies.

Pressurized vascular systems for self-healing materials

PubMed Central

Hamilton, A. R.; Sottos, N. R.; White, S. R.

2012-01-01

An emerging strategy for creating self-healing materials relies on embedded vascular networks of microchannels to transport reactive fluids to regions of damage. Here we investigate the use of active pumping for the pressurized delivery of a two-part healing system, allowing a small vascular system to deliver large volumes of healing agent. Different pumping strategies are explored to improve the mixing and subsequent polymerization of healing agents in the damage zone. Significant improvements in the number of healing cycles and in the overall healing efficiency are achieved compared with prior passive schemes that use only capillary forces for the delivery of healing agents. At the same time, the volume of the vascular system required to achieve this superior healing performance is significantly reduced. In the best case, nearly full recovery of fracture toughness is attained throughout 15 cycles of damage and healing, with a vascular network constituting just 0.1 vol% of the specimen. PMID:21957119

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

PubMed Central

Kim, Min Soo; Yeom, Dong Woo; Kim, Sung Rae; Yoon, Ho Yub; Kim, Chang Hyun; Son, Ho Yong; Kim, Jin Han; Lee, Sangkil; Choi, Young Wook

2017-01-01

A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. PMID:28053506

G2 Autonomous Control for Cryogenic Delivery Systems

NASA Technical Reports Server (NTRS)

Dito, Scott J.

2014-01-01

The Independent System Health Management-Autonomous Control (ISHM-AC) application development for cryogenic delivery systems is intended to create an expert system that will require minimal operator involvement and ultimately allow for complete autonomy when fueling a space vehicle in the time prior to launch. The G2-Autonomous Control project is the development of a model, simulation, and ultimately a working application that will control and monitor the cryogenic fluid delivery to a rocket for testing purposes. To develop this application, the project is using the programming language/environment Gensym G2. The environment is an all-inclusive application that allows development, testing, modeling, and finally operation of the unique application through graphical and programmatic methods. We have learned G2 through training classes and subsequent application development, and are now in the process of building the application that will soon be used to test on cryogenic loading equipment here at the Kennedy Space Center Cryogenics Test Laboratory (CTL). The G2 ISHM-AC application will bring with it a safer and more efficient propellant loading system for the future launches at Kennedy Space Center and eventually mobile launches from all over the world.

The glymphatic system in CNS health and disease: past, present and future

PubMed Central

Plog, Benjamin A.; Nedergaard, Maiken

2018-01-01

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here we review the role of the glymphatic pathway in CNS physiology, factors known to regulate glymphatic flow, and pathologic processes where a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, will also be discussed. PMID:29195051

PEG-PLA-PEG block copolymeric nanoparticles for oral immunization against hepatitis B.

PubMed

Jain, Arvind K; Goyal, Amit K; Mishra, Neeraj; Vaidya, Bhuvaneshwar; Mangal, Sharad; Vyas, Suresh P

2010-03-15

PLA/PLGA nanoparticles are well known as efficient vaccine delivery systems, but they have got limitation in oral vaccine delivery because of their sensitivity to harsh gastric environment. The aim of present study was to improve the stability of PLA nanoparticles in such environment by copolymerizing PLA with PEG. Nanoparticles were formulated using different block copolymers AB, ABA and BAB (where 'A' is PLA and 'B' is PEG) encapsulating hepatitis B surface antigen (HBsAg) to evaluate their efficacy as oral vaccine delivery system. The results of in vitro studies engrave the efficiency of copolymeric nanoparticles to retain encapsulated antigen and average particle size even after 2 h incubation in simulated gastric fluid and simulated intestinal fluid. Fluorescence microscopic studies indicated efficient uptake of copolymeric nanoparticles by gut mucosa of immunized mice model as compared to control. Finally copolymeric and PLA nanoparticles, encapsulating HBsAg, were evaluated for their adjuvancity in generating immune response after oral administration. PLA nanoparticles could not generate an effective immune response due to stability issues. On the other hand, oral administration of copolymeric nanoparticles exhibited effective levels of humoral immunity along with the mucosal (sIgA) and cellular immune response (T(H)1). The results of in vitro and in vivo studies demonstrate that BAB nanoparticles depict enhanced mucosal uptake leading to effective immune response as compared to other copolymeric nanoparticles. Present study indicates the efficacy of BAB nanoparticles as a promising carrier for oral immunization. 2009 Elsevier B.V. All rights reserved.

An Approach to the Design of a Particulate System for Oral Protein Delivery .II. Preparation and Stability Study of rhGH-Loaded Microspheres in Simulated Gastrointestinal Fluids

PubMed Central

Nafissi Varcheh, Nastaran; Aboofazeli, Reza

2011-01-01

The delivery of therapeutic proteins has gained momentum with development of biotechnology. However, large molecular weight, hydrophilic nature and susceptibility to harsh environment of gastrointestinal tract (GIT) resulted in low absorption. The main objective of this work was the design of a particulate system for oral delivery of recombinant human growth hormone (rhGH) on the basis of particle uptake mechanism in GIT. Biodegradable protein-loaded microspheres were prepared using Resomers (RG207, RG756 and RG505) by double emulsion methods. Aqueous solution of protein and freshly prepared rhGH-zinc complex were used for loading process. Various analytical methods, including fluorescence spectroscopy, SDS-PAGE electrophoresis and reversed-phase chromatography, were set up for the quantification and qualification of rhGH before and after the formulation and fabrication procedures. At the optimum conditions, microspheres were mostly below 10 μm with relatively high protein loading (> 50%). Obtained data showed that the stability of protein did not change during the formulation and microencapsulation processes. Results also showed that the encapsulation process in the presence of zinc caused no detectable change in the protein chemical stability. In-vitro stability study of microspheres in different simulated GI media indicated that the entrapped protein was physically stable. Less than 20% of rhGH was released from the microspheres incubated in both simulated stomach and intestine fluids for 3 and 6 h, respectively. PMID:24250342

Errors in fluid balance with pump control of continuous hemodialysis.

PubMed

Roberts, M; Winney, R J

1992-02-01

The use of pumps both proximal and distal to the dialyzer during continuous hemodialysis provides control of dialysate and ultrafiltration flow rates, thereby reducing nursing time. However, we had noted unexpected severe extracellular fluid depletion suggesting that errors in pump delivery may be responsible. We measured in vitro the operation of various pumps under conditions similar to continuous hemodialysis. Fluid delivery of peristaltic and roller pumps varied with how the tubing set was inserted in the pump. Piston and peristaltic pumps with dedicated pump segments were more accurate. Pumps should be calibrated and tested under conditions simulating continuous hemodialysis prior to in vivo use.

Lysimeter methods and apparatus

DOEpatents

Clark, Don T.; Erickson, Eugene E.; Casper, William L.; Everett, David M.; Hubbell, Joel M.; Sisson, James B.

2004-12-07

A suction lysimeter for sampling subsurface liquids includes a lysimeter casing having a drive portion, a reservoir portion, and a tip portion, the tip portion including a membrane through which subsurface liquids may be sampled; a fluid conduit coupled in fluid flowing relation relative to the membrane, and which in operation facilitates the delivery of the sampled subsurface liquids from the membrane to the reservoir portion; and a plurality of tubes coupled in fluid flowing relation relative to the reservoir portion, the tubes in operation facilitating delivery of the sampled subsurface liquids from the reservoir portion for testing. A method of sampling subsurface liquids comprises using this lysimeter.

Using the sessile drop geometry to measure fluid and elastic block copolymer interfaces.

PubMed

Rozairo, Damith P; Croll, Andrew B

2015-02-03

There is considerable interest in the fabrication and mechanics of soft spheres and capsules because of their use in a large number of applications ranging from targeted drug delivery to cosmetically active agents. Many systems, such as lipid and block copolymer vesicles, are already finding considerable industrial use where the performance of soft spheres depends intimately on their mechanics. New advanced features such as fast cargo delivery can be realized only if they fit into the existing mechanical niche of the system in question. Here we present a model system to demonstrate how a capsule structure can be fundamentally changed while maintaining its overall mechanical response as well as a simple, universal method to measure the resulting capsule material properties. Specifically, we use confocal microscopy to adapt the sessile drop geometry to a measurement of the static properties of an ensemble of polystyrene-b-poly(ethylene oxide) (PS-PEO)-stabilized oil droplets. We then synthesize a polystyrene-b-poly(acrylic acid)-b-polystyrene (PS-PAA-PS) elastic-shell-coated emulsion drop that shows an identical deformation to the fluidlike PS-PEO droplets. Both systems, in sessile geometry, can be related to their basic material properties through appropriate modeling. We find that the elastic shell is dominated by its surface tension, easily enabling it to match the static response of a purely fluid drop.

Nanochanneled Device and Related Methods

NASA Technical Reports Server (NTRS)

Goodall, Randy (Inventor); Hosali, Sharath (Inventor); Grattoni, Alessandro (Inventor); Fine, Daniel (Inventor); Hudson, Lee (Inventor); Ferrari, Mauro (Inventor); Liu, Xuewu (Inventor); Medema, Ryan (Inventor)

2013-01-01

A nanochannel delivery device and method of manufacturing and use. The nanochannel delivery device comprises an inlet, an outlet, and a nanochannel. The nanochannel may be oriented parallel to the primary plane of the nanochannel delivery device. The inlet and outlet may be in direct fluid communication with the nanochannel.

A randomized, double-blinded, controlled trial of the effects of fluid rate and/or presence of dextrose in intravenous fluids on the labor course of nulliparas.

PubMed

Fong, Alex; Serra, Allison E; Caballero, Deysi; Garite, Thomas J; Shrivastava, Vineet K

2017-08-01

Prolonged labor has been demonstrated to increase adverse maternal and neonatal outcome. A practice that may decrease the risk of prolonged labor is the modification of fluid intake during labor. Several studies demonstrated that increased hydration in labor as well as addition of dextrose-containing fluids may be associated with a decrease in length of labor. The purpose of our study was to characterize whether high-dose intravenous fluids, standard-dose fluids with dextrose, or high-dose fluids with dextrose show a difference in the duration of labor in nulliparas. Nulliparous subjects with singletons who presented in active labor were randomized to 1 of 3 groups of intravenous fluids: 250 mL/h of normal saline, 125 mL/h of 5% dextrose in normal saline, or 250 mL/h of 2.5% dextrose in normal saline. The primary outcome was total length of labor from initiation of intravenous fluid in vaginally delivered subjects. Secondary outcomes included cesarean delivery rate and length of second stage of labor, among other maternal and neonatal outcomes. In all, 274 subjects who met inclusion criteria were enrolled. There were no differences in baseline characteristics among the 3 groups. There was no difference in the primary outcome of total length of labor in vaginally delivered subjects among the 3 groups. First stage of labor duration, second stage of labor duration, and cesarean delivery rates were also equivalent. There were no differences identified in other secondary outcomes including clinical chorioamnionitis, postpartum hemorrhage, blood loss, Apgar scores, or neonatal intensive care admission. There is no difference in length of labor or delivery outcomes when comparing high-dose intravenous fluids, addition of dextrose, or use of high-dose intravenous fluids with dextrose in nulliparous women who present in active labor. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultrasound-mediated drug delivery for cardiovascular disease

PubMed Central

Sutton, Jonathan T; Haworth, Kevin J; Pyne-Geithman, Gail; Holland, Christy K

2014-01-01

Introduction Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery. Areas covered The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies. Expert opinion These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and less-invasive treatments. PMID:23448121

Optimization of a jet-propelled particle injection system for the uniform transdermal delivery of drug/vaccine.

PubMed

Liu, Yi; Kendall, Mark A F

2007-08-01

A jet-propelled particle injection system, the biolistics, has been developed and employed to accelerate micro-particles for transdermal drug delivery. We have examined a prototype biolistic device employing a converging-diverging supersonic nozzle (CDSN), and found that the micro-particles were delivered with a wide velocity range (200-800 m/s) and spatial distribution. To provide a controllable system for transdermal drug delivery, we present a contoured shock-tube (CST) concept and its embodiment device. The CST configuration utilizes a quasi-steady, quasi-one dimensional and shock-free supersonic flow to deliver the micro-particles with an almost uniform velocity (the mean velocity and the standard deviation, 699 +/- 4.7 m/s) and spatial distribution. The transient gas and particle dynamics in both prototype devices are interrogated with the validated computational fluid dynamics (CFD) approach. The predicted results for static pressure and Mach number histories, gas flow structures, particle velocity distributions and gas-particle interactions are presented and interpreted. The implications for clinical uses are discussed. (c) 2007 Wiley Periodicals, Inc.

Oxygen supersaturated fluid using fine micro/nanobubbles

PubMed Central

Matsuki, Noriaki; Ishikawa, Takuji; Ichiba, Shingo; Shiba, Naoki; Ujike, Yoshihito; Yamaguchi, Takami

2014-01-01

Microbubbles show peculiar properties, such as shrinking collapse, long lifetime, high gas solubility, negative electric charge, and free radical production. Fluids supersaturated with various gases can be easily generated using microbubbles. Oxygen microbubble fluid can be very useful for oxygen delivery to hypoxic tissues. However, there have been no reports of comparative investigations into adding fluids containing oxygen fine micro/nanobubbles (OFM-NBs) to common infusion solutions in daily medical care. In this study, it was demonstrated that OFMNBs can generate oxygen-supersaturated fluids, and they may be sufficiently small to infuse safely into blood vessels. It was found that normal saline solution is preferable for generating an oxygen-rich infusion fluid, which is best administered as a 30-minute intravenous infusion. It was also concluded that dextran solution is suitable for drug delivery substances packing oxygen gas over a 1-hour intravenous infusion. In addition, normal saline solution containing OFMNBs was effective for improving blood oxygenation. Thus, the use of OFMNB-containing fluids is a potentially effective novel method for improving blood oxygenation in cases involving hypoxia, ischemic diseases, infection control, and anticancer chemoradiation therapies. PMID:25285003

Oxygen supersaturated fluid using fine micro/nanobubbles.

PubMed

Matsuki, Noriaki; Ishikawa, Takuji; Ichiba, Shingo; Shiba, Naoki; Ujike, Yoshihito; Yamaguchi, Takami

2014-01-01

Microbubbles show peculiar properties, such as shrinking collapse, long lifetime, high gas solubility, negative electric charge, and free radical production. Fluids supersaturated with various gases can be easily generated using microbubbles. Oxygen microbubble fluid can be very useful for oxygen delivery to hypoxic tissues. However, there have been no reports of comparative investigations into adding fluids containing oxygen fine micro/nanobubbles (OFM-NBs) to common infusion solutions in daily medical care. In this study, it was demonstrated that OFMNBs can generate oxygen-supersaturated fluids, and they may be sufficiently small to infuse safely into blood vessels. It was found that normal saline solution is preferable for generating an oxygen-rich infusion fluid, which is best administered as a 30-minute intravenous infusion. It was also concluded that dextran solution is suitable for drug delivery substances packing oxygen gas over a 1-hour intravenous infusion. In addition, normal saline solution containing OFMNBs was effective for improving blood oxygenation. Thus, the use of OFMNB-containing fluids is a potentially effective novel method for improving blood oxygenation in cases involving hypoxia, ischemic diseases, infection control, and anticancer chemoradiation therapies.

Eudragit® S100 coated calcium pectinate microspheres of curcumin for colon targeting.

PubMed

Zhang, Lin; Cao, Fengliang; Ding, Buyun; Li, Qilu; Xi, Yanwei; Zhai, Guangxi

2011-01-01

Currently, colon-specific drug delivery systems have been investigated for drugs that can exert their bioactivities in the colon. In this study, Eudragit® S100 coated calcium pectinate microsphere, a pH-dependent and enzyme-dependent system, as colon-specific delivery carrier for curcumin was investigated. Curcumin-loaded calcium pectinate microspheres were prepared by emulsification-linkage method, and the preparation technology was optimised by uniform experimental design. The morphology of microspheres was observed under scanning electron microscopy. Interactions between drug and polymers were investigated with differential scanning calorimetry (DSC) and X-ray diffraction. In vitro drug release studies were performed in simulated colonic fluid in the presence of Pectinex Ultra SP-L or 1% (w/v) rat caecal content, and the results indicated that the release of curcumin was significantly increased in the presence of 1% (w/v) rat caecal contents. It could be concluded that Eudragit® S100 coated calcium pectinate microsphere was a potential carrier for colon delivery of curcumin.

Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.

PubMed

Muhammad, Faheem; Wang, Aifei; Qi, Wenxiu; Zhang, Shixing; Zhu, Guangshan

2014-01-01

Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums.

Making Decisions about Service Delivery in Early Childhood Programs

ERIC Educational Resources Information Center

Case-Smith, Jane; Holland, Terri

2009-01-01

Purpose: This article presents a rationale for specialized services personnel to use fluid models of service delivery and explains how specialized services personnel make decisions about the blend of service delivery methods that will best serve a child. Method: The literature on occupational therapy, physical therapy, and speech-language…

The role of the National Launch System in support of Space Station Freedom

NASA Technical Reports Server (NTRS)

Green, J. L.; Saucillo, R. J.; Cirillo, W. M.

1992-01-01

A study was performed to determine the most appropriate potential use of the National Launch System (NLS) for Space Station Freedom (SSF) logistics resupply and growth assembly needs. Objectives were to estimate earth-to-SSF cargo requirements, identify NLS sizing trades, and assess operational constraints of a shuttle and NLS transportation infrastructure. Detailed NLS and Shuttle flight manifests were developed to model varying levels of NLS support. NLS delivery of SSF propellant, and in some cases, cryoenic fluids, yield significant shuttle flight savings with minimum impact to the baseline SSF design. Additional cargo can be delivered by the NLS if SSF trash disposal techniques are employed to limit return cargo requirements. A common vehicle performance level can be used for both logistics resupply and growth hardware delivery.

Lactate in Amniotic Fluid: Predictor of Labor Outcome in Oxytocin-Augmented Primiparas’ Deliveries

PubMed Central

Pembe, Andrea B.; Järnbert-Pettersson, Hans; Norman, Margareta; Wihlbäck, Anna-Carin; Hoesli, Irene; Todesco Bernasconi, Monya; Azria, Elie; Åkerud, Helena; Darj, Elisabet

2016-01-01

Background One of the major complications related to delivery is labor dystocia, or an arrested labor progress. Many dystocic deliveries end vaginally after administration of oxytocin, but a large numbers of women with labor dystocia will undergo a long and unsafe parturition. As a result of the exertion required in labor, the uterus produces lactate. The uterine production of lactate is mirrored by the level of lactate in amniotic fluid (AFL). Objectives To evaluate whether the level of AFL, analysed in a sample of amniotic fluid collected vaginally at arrested labor when oxytocin was needed, could predict labor outcome in nulliparous deliveries. Methods A prospective multicentre study including 3000 healthy primiparous women all with a singleton pregnancy, gestational age 37 to 42 weeks and no maternal /fetal chronic and/or pregnancy-related conditions. A spontaneous onset of labor, regular contractions and cervical dilation ≥ 3 cm were required before the women were invited to take part in the study. Results AFL, analysed within 30 minutes before augmentation, provides information about delivery outcome. Sensitivity for an acute cesarean section according to high (≥10.1mmol/l) or low (< 10.1mmol/l) AFL values was 39.0% (95% CI; 27–50), specificity 90.3% (95% CI; 87–93) PPV 37.3% (95% CI; 27–48) and NPV was 91.0% (95% CI; 88–93). The overall percentage of correct predictions of delivery outcome when the AFL level was used was 83.7%. Deliveries with a high AFL-level correlated with delivery time >12h (p = 0.04), post-partum fever (>38°C, p = 0.01) and post-partum haemorrhage >1.5L (p = 0.04). Conclusion The AFL is a good predictor of delivery outcome in arrested nulliparous deliveries. Low levels of AFL may support the decision to continue a prolonged vaginal labor by augmentation with oxytocin. A high level of AFL correlates with operative interventions and post-partum complications. PMID:27783611

Alginate/polymethacrylate copolymer microparticles for the intestinal delivery of enzymes.

PubMed

Scocca, Sarah; Faustini, Massimo; Villani, Simona; Munari, Eleonora; Conte, Ubaldo; Russo, Vincenzo; Riccardi, Alessia; Vigo, Daniele; Torre, Maria Luisa

2007-04-01

Proteins administered orally must pass through the gastric environment in order to reach their site of absorption in the intestine. How to protect these exogenously administered proteins from the damaging effects of gastric acid and pepsin proteolytic activity, which often induce irreversible structural and functional alterations to the molecules, is an intriguing challenge. Another problem is the physical and chemical instability of proteins during some technological processes, which often involve the use of organic solvents or high temperatures. In this study we investigated the use of alginate microparticles containing one of two enzymes, an enteric polymer and a lyoprotectant for the intestinal delivery of proteins. The two enzymes tested in this protein delivery system were lactate dehydrogenase and alpha-amylase: the former was chosen because of its sensitivity to denaturation, the latter for its relevance in nutrition and medicine. A sodium alginate aqueous solution containing the enteric polymer, a lyoprotectant and the enzyme was either extruded or sprayed into a calcium chloride solution, with the resultant formation of beads and microspheres which were freeze-dried. About 90% of the enzyme activity was maintained during the process of loading the proteins into the microparticles and the subsequent freeze-drying process. The stability of the encapsulated enzyme in an acid medium and the enzymatic activity in an intestinal environment were then investigated by a dissolution test. This consisted of exposing the microparticles to simulated gastric fluid (pH 1.2) for 2 hours and to simulated intestinal fluid (pH 7.5+/-0.1) for 1 hour. The morphology of the microparticles did not change in the acid environment, whereas they completely dissolved within 3 min in the simulated intestinal fluid. Residual enzymatic activity after the test remained satisfactory for both enzymes. In conclusion, these microparticle systems offer promise for applications in human and veterinary medicine as well as in human and animal nutrition.

Voxelized Computational Model for Convection-Enhanced Delivery in the Rat Ventral Hippocampus: Comparison with In Vivo MR Experimental Studies

PubMed Central

Kim, Jung Hwan; Astary, Garrett W.; Kantorovich, Svetlana; Mareci, Thomas H.; Carney, Paul R.; Sarntinoranont, Malisa

2012-01-01

Convection-enhanced delivery (CED) is a promising local delivery technique for overcoming the blood–brain barrier (BBB) and treating diseases of the central nervous system (CNS). For CED, therapeutics are infused directly into brain tissue and the drug agent is spread through the extracellular space, considered to be highly tortuous porous media. In this study, 3D computational models developed using magnetic resonance (MR) diffusion tensor imaging data sets were used to predict CED transport in the rat ventral hippocampus using a voxelized modeling previously developed by our group. Predicted albumin tracer distributions were compared with MR-measured distributions from in vivo CED in the ventral hippocampus up to 10 μL of Gd-DTPA albumin tracer infusion. Predicted and measured tissue distribution volumes and distribution patterns after 5 and 10 μL infusions were found to be comparable. Tracers were found to occupy the underlying landmark structures with preferential transport found in regions with less fluid resistance such as the molecular layer of the dentate gyrus. Also, tracer spread was bounded by high fluid resistance layers such as the granular cell layer and pyramidal cell layer of dentate gyrus. Leakage of tracers into adjacent CSF spaces was observed towards the end of infusions. PMID:22532321

Template-directed hydrothermal synthesis of hydroxyapatite as a drug delivery system for the poorly water-soluble drug carvedilol

NASA Astrophysics Data System (ADS)

Zhao, Qinfu; Wang, Tianyi; Wang, Jing; Zheng, Li; Jiang, Tongying; Cheng, Gang; Wang, Siling

2011-09-01

In order to improve the dissolution rate and increase the bioavailability of a poorly water-soluble drug, intended to be administered orally, the biocompatible and bioactive mesoporous hydroxyapatite (HA) was successfully synthesized. In the present study, mesoporous HA nanoparticles were produced using Pluronic block co-polymer F127 and cetyltrimethylammonium bromide (CTAB) as templates by the hydrothermal method. The obtained mesoporous HA was employed as a drug delivery carrier to investigate the drug storage/release properties using carvedilol (CAR) as a model drug. Characterizations of the raw CAR powder, mesoporous HA and CAR-loaded HA were carried out by the scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, N2 adsorption/desorption, thermogravimetric analysis (TGA), and UV-VIS spectrophotometry. The results demonstrated that CAR was successfully incorporated into the mesoporous HA host. In vitro drug release studies showed that mesoporous HA had a high drug load efficiency and provided immediate release of CAR compared with micronized raw drug in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). Consequently, mesoporous HA is a good candidate as a drug carrier for the oral delivery of poorly water-soluble drugs.

Comparison of different zeolite framework types as carriers for the oral delivery of the poorly soluble drug indomethacin.

PubMed

Karavasili, Christina; Amanatiadou, Elsa P; Kontogiannidou, Eleni; Eleftheriadis, Georgios K; Bouropoulos, Nikolaos; Pavlidou, Eleni; Kontopoulou, Ioanna; Vizirianakis, Ioannis S; Fatouros, Dimitrios G

2017-08-07

Microporous zeolites of distinct framework types, textural properties and crystal morphologies namely BEA, ZSM and NaX, have been employed as carriers to assess their effect on modulating the dissolution behavior of a BCS II model drug (indomethacin). Preparation of the loaded carriers via the incipient wetness method induced significant drug amorphization for the BEA and NaX samples, as well as high drug payloads. The stability of the amorphous drug content was retained after stressing test evaluation of the porous carriers. The dissolution profile of loaded indomethacin was evaluated in simulated gastric fluid (pH 1.2) and simulated intestinal fluids FaSSIF (fasted) and FeSSIF (fed state) conditions and was found to be dependent on the aluminosilicate ratio of the zeolites and the degree of crystalline drug content. The feasibility of the zeolitic particles as oral drug delivery systems was appraised with cytocompatibility and cellular toxicity studies in Caco-2 cultures in a time- and dose-dependent manner by means of the MTT assay and flow cytometry analysis, respectively. Intracellular accumulation of the zeolite particles was observed with no apparent cytotoxic effects at the lower concentrations tested, rendering such microporous zeolites pertinent candidates in oral drug delivery applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of Computational Fluid Dynamics and Coupled Fluid-Solid Modeling for a Direct Transfer Preswirl System.

PubMed

Javiya, Umesh; Chew, John; Hills, Nick; Dullenkopf, Klaus; Scanlon, Timothy

2013-05-01

The prediction of the preswirl cooling air delivery and disk metal temperature are important for the cooling system performance and the rotor disk thermal stresses and life assessment. In this paper, standalone 3D steady and unsteady computation fluid dynamics (CFD), and coupled FE-CFD calculations are presented for prediction of these temperatures. CFD results are compared with previous measurements from a direct transfer preswirl test rig. The predicted cooling air temperatures agree well with the measurement, but the nozzle discharge coefficients are under predicted. Results from the coupled FE-CFD analyses are compared directly with thermocouple temperature measurements and with heat transfer coefficients on the rotor disk previously obtained from a rotor disk heat conduction solution. Considering the modeling limitations, the coupled approach predicted the solid metal temperatures well. Heat transfer coefficients on the rotor disk from CFD show some effect of the temperature variations on the heat transfer coefficients. Reasonable agreement is obtained with values deduced from the previous heat conduction solution.

Manufacturing Solid Dosage Forms from Bulk Liquids Using the Fluid-bed Drying Technology.

PubMed

Qi, Jianping; Lu, Y I; Wu, Wei

2015-01-01

Solid dosage forms are better than liquid dosage forms in many ways, such as improved physical and chemical stability, ease of storage and transportation, improved handling properties, and patient compliance. Therefore, it is required to transform dosage forms of liquid origins into solid dosage forms. The functional approaches are to absorb the liquids by solid excipients or through drying. The conventional drying technologies for this purpose include drying by heating, vacuum-, freeze- and spray-drying, etc. Among these drying technologies, fluidbed drying emerges as a new technology that possesses unique advantages. Fluid-bed drying or coating is highly efficient in solvent removal, can be performed at relatively low temperatures, and is a one-step process to manufacture formulations in pellet forms. In this article, the status of the art of manufacturing solid dosage forms from bulk liquids by fluid-bed drying technology was reviewed emphasizing on its application in solid dispersion, inclusion complexes, self-microemulsifying systems, and various nanoscale drug delivery systems.

Stability of plant virus-based nanocarriers in gastrointestinal fluids† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7nr07182e

PubMed Central

Evans, David J.; Baldelli Bombelli, Francesca; Lomonossoff, George P.

2018-01-01

Cowpea mosaic virus (CPMV) is a plant virus which is being extensively investigated as a drug delivery and vaccine nanocarrier for parenteral administration. However, to date little is known about the suitability of plant-based nanocarriers for oral delivery. In this study, the colloidal (i.e. aggregation), physical (i.e. denaturation) and chemical (i.e. digestion of the polypeptides) stability of CPMV and its empty virus-like particles (eVLPs) in conditions resembling the gastrointestinal fluids were evaluated. The nanoparticles were incubated in various simulated gastric and intestinal fluids and in pig gastric and intestinal fluids. CPMV and eVLPs had similar stabilities. In simulated gastric media, they were stable at pH ≥ 2.5. At lower pH destabilisation of the particle structure occurred, which, in turn, rendered the polypeptides extremely sensitive to pepsin digestion. However, both CPMV and eVLPs were stable in simulated intestinal fluids, in pig gastric fluids and in pig intestinal fluids. Thus CPMV, despite being a protein-based nanoparticle, was much more resistant to the harsh GI conditions than soluble proteins. Remarkably, both CPMV and eVLPs incubated in pig gastric and intestinal fluids were not subject to protein adsorption, with no formation of a detectable protein corona. The lack of a protein corona on CPMV and eVLP surfaces in GI fluids would imply that, if orally administered, these nanoparticles could maintain their native surface characteristics; thus, their biological interactions would remain predictable and unchanged. In summary, CPMV and eVLPs can be considered promising nanocarriers for applications requiring oral delivery, given their chemical, physical and colloidal stability and lack of protein adsorption from the environment in most of the tested conditions. PMID:29231944

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.

Combined lentiviral and RNAi technologies for the delivery and permanent silencing of the hsp25 gene.

PubMed

Kaur, Punit; Nagaraja, Ganachari M; Asea, Alexzander

2011-01-01

Elevated heat shock protein 27 (Hsp27) expression has been found in a number of tumors, including breast, prostate, gastric, uterine, ovarian, head and neck, and tumor arising from the nervous system and urinary system, and determined to be a predictor of poor clinical outcome. Although the mechanism of action of Hsp27 has been well documented, there are currently no available inhibitors of Hsp27 in clinical trials. RNA interference (RNAi) has the potential to offer more specificity and flexibility than traditional drugs to silence gene expression. Not surprisingly, RNAi has become a major focus for biotechnology and pharmaceutical companies, which are now in the early stages of developing RNAi therapeutics, mostly based on short interfering RNA (siRNAs), to target viral infection, cancer, hypercholesterolemia, cardiovascular disease, macular degeneration, and neurodegenerative diseases. However, the critical issues associated with RNAi as a therapeutic are delivery, specificity, and stability of the RNAi reagents. To date, the delivery is currently considered the biggest hurdle, as the introduction of siRNAs systemically into body fluids can result in their degradation, off-target effects, and immune detection. In this chapter, we discuss a method of combined lentiviral and RNAi-based technology for the delivery and permanent silencing of the hsp25 gene.

Evaluation of synthetic zeolites as oral delivery vehicle for anti-inflammatory drugs

PubMed Central

Khodaverdi, Elham; Honarmandi, Reza; Alibolandi, Mona; Baygi, Roxana Rafatpanah; Hadizadeh, Farzin; Zohuri, Gholamhossein

2014-01-01

Objective(s): In this research, zeolite X and zeolite Y were used as vehicle to prepare intestine targeted oral delivery systems of indomethacin and ibuprofen. Materials and Methods: A soaking procedure was implemented to encapsulate indomethacin or ibuprofen within synthetic zeolites. Gravimetric methods and IR spectra of prepared formulations were used to assess drug loading efficiencies into zeolite structures. Scanning Electron Microscopy (SEM) was also utilized to determine morphologies changes in synthetic zeolites after drug loading. At the next stage, dissolution studies were used to predict the in vivo performance of prepared formulations at HCl 0.1 N and PBS pH 6.5 as simulated gastric fluid (SGF) and simulated intestine fluid (SIF), respectively. Results: Drug loadings of prepared formulations was determined between 24-26 % w/w. Dissolution tests at SGF were shown that zeolites could retain acidic model drugs in their porous structures and can be able to limit their release into the stomach. On the other hand, all prepared formulations completely released model drugs during 3 hr in simulated intestine fluid. Conclusion: Obtained results indicated zeolites could potentially be able to release indomethacin and ibuprofen in a sustained and controlled manner and reduced adverse effects commonly accompanying oral administrations of NSAIDs. PMID:24967062

Optimization of a Biomimetic Apatite Nanoparticle Delivery System for Non-viral Gene Transfection---a Simulated Body Fluid Approach

NASA Astrophysics Data System (ADS)

Das, Debobrato

Current methods for gene delivery utilize nanocarriers such as liposomes and viral vectors that may produce in vivo toxicity, immunogenicity, or mutagenesis. Moreover, these common high-cost systems have a low efficacy of gene-vehicle transport across the cell plasma membrane followed by inadequate release and weak intracellular stability of the genetic sequence. Thus, this study aims to maximize gene transfection while minimizing cytotoxicity by utilizing supersaturated blood-plasma ions derived from simulated body fluids (SBF). With favorable electrostatic interactions to create biocompatible calcium-phosphate nanoparticles (NPs) derived from biomimetic apatite (BA), results suggest that the SBF system, though naturally sensitive to reaction conditions, after optimization can serve as a tunable and versatile platform for the delivery of various types of nucleic acids. From a systematic exploration of the effects of nucleation pH, incubation temperature, and time on transfection efficiency, the study proposes distinct characteristic trends in SBF BA-NP morphology, cellular uptake, cell viability, and gene modulation. Specifically, with aggressive nucleation and growth of BA-NPs in solution (observed via scanning electron microscopy), the ensuing microenvironment imposes a more toxic cellular interaction (indicated by alamarBlue and BCA assays), limiting particle uptake (fluorescence experiments) and subsequent gene knockdown (quantitative loss of function assays). Controlled precipitation of BA-NPs function to increase particle accessibility by surrounding cells, and subsequently enhance uptake and transfection efficiency. By closely examining such trends, an optimal fabrication condition of pH 6.5-37C can be observed where particle growth is more tamed and less chaotic, providing improved, favorable cellular interactions that increase cell uptake and consequently maximize gene transfection, without compromising cellular viability.

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

Recovering from Delivery

MedlinePlus

... enough fluids is to have a glass of water whenever your baby nurses. At least until your milk supply is well established, try to avoid caffeine, which causes loss of fluid through urine and sometimes makes babies ...

Cochlear pharmacokinetics with local inner ear drug delivery using a three-dimensional finite-element computer model.

PubMed

Plontke, Stefan K; Siedow, Norbert; Wegener, Raimund; Zenner, Hans-Peter; Salt, Alec N

2007-01-01

Cochlear fluid pharmacokinetics can be better represented by three-dimensional (3D) finite-element simulations of drug dispersal. Local drug deliveries to the round window membrane are increasingly being used to treat inner ear disorders. Crucial to the development of safe therapies is knowledge of drug distribution in the inner ear with different delivery methods. Computer simulations allow application protocols and drug delivery systems to be evaluated, and may permit animal studies to be extrapolated to the larger cochlea of the human. A finite-element 3D model of the cochlea was constructed based on geometric dimensions of the guinea pig cochlea. Drug propagation along and between compartments was described by passive diffusion. To demonstrate the potential value of the model, methylprednisolone distribution in the cochlea was calculated for two clinically relevant application protocols using pharmacokinetic parameters derived from a prior one-dimensional (1D) model. In addition, a simplified geometry was used to compare results from 3D with 1D simulations. For the simplified geometry, calculated concentration profiles with distance were in excellent agreement between the 1D and the 3D models. Different drug delivery strategies produce very different concentration time courses, peak concentrations and basal-apical concentration gradients of drug. In addition, 3D computations demonstrate the existence of substantial gradients across the scalae in the basal turn. The 3D model clearly shows the presence of drug gradients across the basal scalae of guinea pigs, demonstrating the necessity of a 3D approach to predict drug movements across and between scalae with larger cross-sectional areas, such as the human, with accuracy. This is the first model to incorporate the volume of the spiral ligament and to calculate diffusion through this structure. Further development of the 3D model will have to incorporate a more accurate geometry of the entire inner ear and incorporate more of the specific processes that contribute to drug removal from the inner ear fluids. Appropriate computer models may assist in both drug and drug delivery system design and can thus accelerate the development of a rationale-based local drug delivery to the inner ear and its successful establishment in clinical practice. Copyright 2007 S. Karger AG, Basel.

Cochlear Pharmacokinetics with Local Inner Ear Drug Delivery Using a Three-Dimensional Finite-Element Computer Model

PubMed Central

Plontke, Stefan K.; Siedow, Norbert; Wegener, Raimund; Zenner, Hans-Peter; Salt, Alec N.

2006-01-01

Hypothesis: Cochlear fluid pharmacokinetics can be better represented by three-dimensional (3D) finite-element simulations of drug dispersal. Background: Local drug deliveries to the round window membrane are increasingly being used to treat inner ear disorders. Crucial to the development of safe therapies is knowledge of drug distribution in the inner ear with different delivery methods. Computer simulations allow application protocols and drug delivery systems to be evaluated, and may permit animal studies to be extrapolated to the larger cochlea of the human. Methods: A finite-element 3D model of the cochlea was constructed based on geometric dimensions of the guinea pig cochlea. Drug propagation along and between compartments was described by passive diffusion. To demonstrate the potential value of the model, methylprednisolone distribution in the cochlea was calculated for two clinically relevant application protocols using pharmacokinetic parameters derived from a prior one-dimensional (1D) model. In addition, a simplified geometry was used to compare results from 3D with 1D simulations. Results: For the simplified geometry, calculated concentration profiles with distance were in excellent agreement between the 1D and the 3D models. Different drug delivery strategies produce very different concentration time courses, peak concentrations and basal-apical concentration gradients of drug. In addition, 3D computations demonstrate the existence of substantial gradients across the scalae in the basal turn. Conclusion: The 3D model clearly shows the presence of drug gradients across the basal scalae of guinea pigs, demonstrating the necessity of a 3D approach to predict drug movements across and between scalae with larger cross-sectional areas, such as the human, with accuracy. This is the first model to incorporate the volume of the spiral ligament and to calculate diffusion through this structure. Further development of the 3D model will have to incorporate a more accurate geometry of the entire inner ear and incorporate more of the specific processes that contribute to drug removal from the inner ear fluids. Appropriate computer models may assist in both drug and drug delivery system design and can thus accelerate the development of a rationale-based local drug delivery to the inner ear and its successful establishment in clinical practice. PMID:17119332

Buccal drug delivery technologies for patient-centred treatment of radiation-induced xerostomia (dry mouth).

PubMed

Malallah, Osamah S; Garcia, Cristina M Aller; Proctor, Gordon B; Forbes, Ben; Royall, Paul G

2018-04-25

Radiotherapy is a life-saving treatment for head and neck cancers, but almost 100% of patients develop dry mouth (xerostomia) because of radiation-induced damage to their salivary glands. Patients with xerostomia suffer symptoms that severely affect their health as well as physical, social and emotional aspects of their life. The current management of xerostomia is the application of saliva substitutes or systemic delivery of saliva-stimulating cholinergic agents, including pilocarpine, cevimeline or bethanechol tablets. It is almost impossible for substitutes to replicate all the functional and sensory facets of natural saliva. Salivary stimulants are a better treatment option than saliva substitutes as the former induce the secretion of natural saliva from undamaged glands; typically, these are the minor salivary glands. However, patients taking cholinergic agents systemically experience pharmacology-related side effects including sweating, excessive lacrimation and gastrointestinal tract distresses. Local delivery direct to the buccal mucosa has the potential to provide rapid onset of drug action, i.e. activation of minor salivary glands within the buccal mucosa, while sparing systemic drug exposure and off-target effects. This critical review of the technologies for the local delivery of saliva-stimulating agents includes oral disintegrating tablets (ODTs), oral disintegrating films, medicated chewing gums and implantable drug delivery devices. Our analysis makes a strong case for the development of ODTs for the buccal delivery of cholinergic agents: these must be patient-friendly delivery platforms with variable loading capacities that release the drug rapidly in fluid volumes typical of residual saliva in xerostomia (0.05-0.1 mL). Copyright © 2018 Elsevier B.V. All rights reserved.

Gastrin levels in mothers and neonates at delivery in various perinatal conditions.

PubMed

Morán, C; Carranza-Lira, S; Ochoa, R; Martínez, J C; Herrera, M; Fonseca, E; Zárate, A

1996-08-01

This study was designed to assess the variations of gastrin (Ga) serum levels in mothers and newborns at birth in some perinatal disorders. Ga levels were measured by RIA in maternal serum, amniotic fluid and cord sera of newborns in 55 cases with the following conditions: normal pregnancy and eutocic vaginal delivery (n = 8), repeat cesarean section (n = 10), and cardiotogographic register suggestive of fetal compromise (n = 15), cephalopelvic disproportion (n = 8), preeclampsia (n = 7) and postdate pregnancy (n = 7). Statistical analysis was performed by Mann-Whitney U test. Ga levels in cord sera of newborn and amniotic fluid in normal pregnancy and eutocic delivery were significantly higher (p < 0.02 and p < 0.01, respectively) than those found in patients with repeat cesarean operation. Serum Ga concentrations in women with postterm pregnancy were significantly higher (p < 0.02) than in women with prior cesarean section. Ga levels in amniotic fluid samples in the presence of suspected fetal compromise and postdate pregnancy were significantly higher (p < 0.001) than those observed in women who had repeat cesarean operation. Vaginal delivery and perinatal pathology may induce hypergastrinemia in both mother and neonate at birth.

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

PubMed Central

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-01-01

Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system. PMID:16930490

Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

PubMed

Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

2006-08-24

Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery system.

Fuel injection and mixing systems and methods of using the same

DOEpatents

Mao, Chien-Pei; Short, John

2010-08-03

A fuel injection and mixing system is provided. The system includes an injector body having a fuel inlet and a fuel outlet, and defines a fuel flow path between the inlet and outlet. The fuel flow path may include a generally helical flow passage having an inlet end portion disposed proximate the fuel inlet of the injector body. The flow path also may include an expansion chamber downstream from and in fluid communication with the helical flow passage, as well as a fuel delivery device in fluid communication with the expansion chamber for delivering fuel. Heating means is also provided in thermal communication with the injector body. The heating means may be adapted and configured for maintaining the injector body at a predetermined temperature to heat fuel traversing the flow path. A method of preheating and delivering fuel is also provided.

Influence of vascular normalization on interstitial flow and delivery of liposomes in tumors

NASA Astrophysics Data System (ADS)

Ozturk, Deniz; Yonucu, Sirin; Yilmaz, Defne; Burcin Unlu, Mehmet

2015-02-01

Elevated interstitial fluid pressure is one of the barriers of drug delivery in solid tumors. Recent studies have shown that normalization of tumor vasculature by anti-angiogenic factors may improve the delivery of conventional cytotoxic drugs, possibly by increasing blood flow, decreasing interstitial fluid pressure, and enhancing the convective transvascular transport of drug molecules. Delivery of large therapeutic agents such as nanoparticles and liposomes might also benefit from normalization therapy since their transport depends primarily on convection. In this study, a mathematical model is presented to provide supporting evidence that normalization therapy may improve the delivery of 100 nm liposomes into solid tumors, by both increasing the total drug extravasation and providing a more homogeneous drug distribution within the tumor. However these beneficial effects largely depend on tumor size and are stronger for tumors within a certain size range. It is shown that this size effect may persist under different microenvironmental conditions and for tumors with irregular margins or heterogeneous blood supply.

A Wireless Text Messaging System Improves Communication for Neonatal Resuscitation.

PubMed

Hughes Driscoll, Colleen A; Schub, Jamie A; Pollard, Kristi; El-Metwally, Dina

Handoffs for neonatal resuscitation involve communicating critical delivery information (CDI). The authors sought to achieve ≥95% communication of CDI during resuscitation team requests. CDI included name of caller, urgency of request, location of delivery, gestation of fetus, status of amniotic fluid, and indication for presence of the resuscitation team. Three interventions were implemented: verbal scripted handoff, Spök text messaging, and Engage text messaging. Percentages of CDI communications were analyzed using statistical process control. Following implementation of Engage, the communication of all CDI, except for indication, was ≥95%; communication of indication occurred 93% of the time. Control limits for most CDI were narrower with Engage, indicating greater reliability of communication compared to the verbal handoff and Spök. Delayed resuscitation team arrival, a countermeasure, was not higher with text messaging compared to verbal handoff ( P = 1.00). Text messaging improved communication during high-risk deliveries, and it may represent an effective tool for other delivery centers.

Hydrogel-Forming Microneedle Arrays for Enhanced Transdermal Drug Delivery

PubMed Central

Donnelly, Ryan F; Singh, Thakur Raghu Raj; Garland, Martin J; Migalska, Katarzyna; Majithiya, Rita; McCrudden, Cian M; Kole, Prashant Laxman; Mahmood, Tuan Mazlelaa Tuan; McCarthy, Helen O; Woolfson, A David

2012-01-01

Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients. PMID:23606824

Osmolarity as a contributing factor in topical drug delivery

NASA Astrophysics Data System (ADS)

Funke, Claire; Szeri, Andrew J.

2017-11-01

Gels and dissolvable solids are drug delivery platforms being evaluated for application of active pharmaceutical ingredients, termed microbicides, which act topically against infection by sexually transmitted HIV. In previous work, we have investigated how dilution by naturally produced fluid from the vaginal mucosa affects drug transport into the vaginal wall. We expand on this work by no longer assuming a constant flux and instead developing a relation for fluid transport based on osmolarity - thus allowing fluid to pass both into and out of epithelial cells. This relation shows that varying the osmolarity of the applied solution can have a significant effect on the amount of drug delivered to its target while holding the applied amount constant. This effect is modulated by a dimensionless group that relates the rates of solute and solvent transport. Ultimately, our goal is to develop a tool to understand better how to manipulate solution osmolarity in order to improve drug delivery within safety parameters for mucosal tissue.

Bacteriuria in Pregnancy and Infection in Amniotic Fluid and Infant

PubMed Central

Ives, J. A.; Abbott, G. D.; Bailey, R. R.

1971-01-01

Women with asymptomatic bacteriuria during pregnancy had sterile amniotic fluid at the time of delivery. There was no evidence that maternal urinary infection was associated with infection in the infant. PMID:5555492

EMERGING MICROTECHNOLOGIES FOR THE DEVELOPMENT OF ORAL DRUG DELIVERY DEVICES

PubMed Central

Chirra, Hariharasudhan D.; Desai, Tejal A.

2012-01-01

The development of oral drug delivery platforms for administering therapeutics in a safe and effective manner across the gastrointestinal epithelium is of much importance. A variety of delivery systems such as enterically coated tablets, capsules, particles, and liposomes have been developed to improve oral bioavailability of drugs. However, orally administered drugs suffer from poor localization and therapeutic efficacy due to various physiological conditions such as low pH, and high shear intestinal fluid flow. Novel platforms combining controlled release, improved adhesion, tissue penetration, and selective intestinal targeting may overcome these issues and potentially diminish the toxicity and high frequency of administration associated with conventional oral delivery. Microfabrication along with appropriate surface chemistry, provide a means to fabricate these platforms en masse with flexibility in tailoring the shape, size, reservoir volume, and surface characteristics of microdevices. Moreover, the same technology can be used to include integrated circuit technology and sensors for designing sophisticated autonomous drug delivery devices that promise to significantly improve point of care diagnostic and therapeutic medical applications. This review sheds light on some of the fabrication techniques and addresses a few of the microfabricated devices that can be effectively used for controlled oral drug delivery applications. PMID:22981755

Fluorescent Microscope System to Monitor Real-Time Interactions between Focused Ultrasound, Echogenic Drug Delivery Vehicles, and Live Cell Membranes

PubMed Central

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

2012-01-01

Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5 MPa the membranes were shown to completely fragment while at intensities below 1 MPa there is a popping and slow unfolding. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20 μm from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery. PMID:22749476

Fluorescent microscope system to monitor real-time interactions between focused ultrasound, echogenic drug delivery vehicles, and live cell membranes.

PubMed

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

2013-01-01

Rapid development in the field of ultrasound triggered drug delivery has made it essential to study the real-time interaction between the membranes of live cells and the membranes of echogenic delivery vehicles under exposure to focused ultrasound. The objective of this work was to design an analysis system that combined fluorescent imagining, high speed videography, and definable pulse sequences of focused ultrasound to allow for real time observations of both cell and vehicle membranes. Documenting the behavior of the membranes themselves has not previously been possible due to limitations with existing optical systems used to understand the basic physics of microbubble/ultrasound interaction and the basic interaction between microbubbles and cells. The performance of this new system to monitor membrane behavior was demonstrated by documenting the modes of vehicle fragmentation at different ultrasound intensity levels. At 1.5MPa the membranes were shown to completely fragment while at intensities below 1MPa the membranes pop open and slowly unfold. The interaction between these vehicles and cell membranes was also documented by the removal of fluorescent particles from the surfaces of live cells out to 20μm from the microbubble location. The fluid flow created by microstreaming around ensonated microbubbles was documented at video recording speeds from 60 to 18,000 frames per second. This information about membrane behavior allows the chemical and physical properties of the drug delivery vehicle to be designed along with the ultrasound pulse sequence to cause the most efficient drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair.

PubMed

Sharma, Aruna; Menon, Preeti; Muresanu, Dafin F; Ozkizilcik, Asya; Tian, Z Ryan; Lafuente, José V; Sharma, Hari S

2016-01-01

The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.

Experimental verification of theoretical equations for acoustic radiation force on compressible spherical particles in traveling waves.

PubMed

Johnson, Kennita A; Vormohr, Hannah R; Doinikov, Alexander A; Bouakaz, Ayache; Shields, C Wyatt; López, Gabriel P; Dayton, Paul A

2016-05-01

Acoustophoresis uses acoustic radiation force to remotely manipulate particles suspended in a host fluid for many scientific, technological, and medical applications, such as acoustic levitation, acoustic coagulation, contrast ultrasound imaging, ultrasound-assisted drug delivery, etc. To estimate the magnitude of acoustic radiation forces, equations derived for an inviscid host fluid are commonly used. However, there are theoretical predictions that, in the case of a traveling wave, viscous effects can dramatically change the magnitude of acoustic radiation forces, which make the equations obtained for an inviscid host fluid invalid for proper estimation of acoustic radiation forces. To date, experimental verification of these predictions has not been published. Experimental measurements of viscous effects on acoustic radiation forces in a traveling wave were conducted using a confocal optical and acoustic system and values were compared with available theories. Our results show that, even in a low-viscosity fluid such as water, the magnitude of acoustic radiation forces is increased manyfold by viscous effects in comparison with what follows from the equations derived for an inviscid fluid.

Experimental verification of theoretical equations for acoustic radiation force on compressible spherical particles in traveling waves

NASA Astrophysics Data System (ADS)

Johnson, Kennita A.; Vormohr, Hannah R.; Doinikov, Alexander A.; Bouakaz, Ayache; Shields, C. Wyatt; López, Gabriel P.; Dayton, Paul A.

2016-05-01

Acoustophoresis uses acoustic radiation force to remotely manipulate particles suspended in a host fluid for many scientific, technological, and medical applications, such as acoustic levitation, acoustic coagulation, contrast ultrasound imaging, ultrasound-assisted drug delivery, etc. To estimate the magnitude of acoustic radiation forces, equations derived for an inviscid host fluid are commonly used. However, there are theoretical predictions that, in the case of a traveling wave, viscous effects can dramatically change the magnitude of acoustic radiation forces, which make the equations obtained for an inviscid host fluid invalid for proper estimation of acoustic radiation forces. To date, experimental verification of these predictions has not been published. Experimental measurements of viscous effects on acoustic radiation forces in a traveling wave were conducted using a confocal optical and acoustic system and values were compared with available theories. Our results show that, even in a low-viscosity fluid such as water, the magnitude of acoustic radiation forces is increased manyfold by viscous effects in comparison with what follows from the equations derived for an inviscid fluid.

A Review on Phytosome Technology as a Novel Approach to Improve The Bioavailability of Nutraceuticals

NASA Astrophysics Data System (ADS)

Amin, Tawheed; Bhat, Suman Vikas

2012-08-01

The bioavailability and absorption of water soluble phytoconstituents is erratic due to poor solubility of these constituents in gastrointestinal tract. This can be overcome by a novel delivery system known as phytosome technology in which water soluble phytoconstituents are allowed to react with phospholipids. For better and improved bioavailability, natural phytoconstituents must have a good balance between hydrophilicity (helps in dissolution in gastro-intestinal fluids) and hydrophobicity (helps to cross lipid rich cell membranes). This is achieved through phytosome technology. Phospholipids have a dual solubility and acts as an emulsifier. Phytosome technology acts as a bridge between novel and conventional delivery systems. Many products are available in the market based on this phytosome technology which include popular herbal extracts such as Ginkgo biloba, Silybum marianum, grape seed, olive oil flavonoids etc.

Numerical Investigation of Oxygenated and Deoxygenated Blood Flow through a Tapered Stenosed Arteries in Magnetic Field.

PubMed

Abdollahzadeh Jamalabadi, M Y; Akbari Bidokhti, Amin Ali; Khak Rah, Hamid; Vaezi, Siavash; Hooshmand, Payam

2016-01-01

Current paper is focused on transient modeling of blood flow through a tapered stenosed arteries surrounded a by solenoid under the presence of heat transfer. The oxygenated and deoxygenated blood are considered here by the Newtonian and Non-Newtonian fluid (power law and Carreau-Yasuda) models. The governing equations of bio magnetic fluid flow for an incompressible, laminar, homogeneous, non-Newtonian are solved by finite volume method with SIMPLE algorithm for structured grid. Both magnetization and electric current source terms are well thought-out in momentum and energy equations. The effects of fluid viscosity model, Hartmann number, and magnetic number on wall shear stress, shearing stress at the stenosis throat and maximum temperature of the system are investigated and are optimized. The current study results are in agreement with some of the existing findings in the literature and are useful in thermal and mechanical design of spatially varying magnets to control the drug delivery and biomagnetic fluid flows through tapered arteries.

Fluid-driven reciprocating apparatus and valving for controlling same

DOEpatents

Whitehead, John C.; Toews, Hans G.

1993-01-01

A control valve assembly for alternately actuating a pair of fluid-driven free-piston devices by using fluid pressure communication therebetween. Each control valve is switched by a pressure signal depending on the state of its counterpart's piston. The communication logic is arranged to provide overlap of the forward strokes of the pistons, so that at least one of the pair will always be pressurized. Thus, uninterrupted pumping of liquid is made possible from a pair of free-piston pumps. In addition, the speed and frequency of piston stroking is entirely dependent on the mechanical power load applied. In the case of a pair of pumps, this enables liquid delivery at a substantially constant pressure over the full range of flow rates, from zero to maximum flow. One embodiment of the invention utilized two pairs of fluid-driven free-piston devices whereby a bipropellant liquid propulsion system may be operated, so as to provide continuous flow of both fuel and oxidizer liquids when used in rocket applications, for example.

Development of a floating drug delivery system with superior buoyancy in gastric fluid using hot-melt extrusion coupled with pressurized CO₂.

PubMed

Almutairy, B K; Alshetaili, A S; Ashour, E A; Patil, H; Tiwari, R V; Alshehri, S M; Repka, M A

2016-03-01

The present study aimed to develop a continuous single-step manufacturing platform to prepare a porous, low-density, and floating multi-particulate system (mini-tablet, 4 mm size). This process involves injecting inert, non-toxic pressurized CO₂gas (P-CO₂) in zone 4 of a 16-mm hot-melt extruder (HME) to continuously generate pores throughout the carrier matrix. Unlike conventional methods for preparing floating drug delivery systems, additional chemical excipients and additives are not needed in this approach to create minute openings on the surface of the matrices. The buoyancy efficiency of the prepared floating system (injection of P-CO₂) in terms of lag time (0 s) significantly improved (P < 0.05), compared to the formulation prepared by adding the excipient sodium bicarbonate (lag time 120 s). The main advantages of this novel manufacturing technique include: (i) no additional chemical excipients need to be incorporated in the formulation, (ii) few manufacturing steps are required, (iii) high buoyancy efficiency is attained, and (iv) the extrudate is free of toxic solvent residues. Floating mini-tablets containing acetaminophen (APAP) as a model drug within the matrix-forming carrier (Eudragit® RL PO) have been successfully processed via this combined technique (P-CO₂/HME). Desired controlled release profile of APAP from the polymer Eudragit® RL PO is attained in the optimized formulation, which remains buoyant on the surface of gastric fluids prior to gastric emptying time (average each 4 h).

Enzyme-Powered Pumps: From Fundamentals to Applications

NASA Astrophysics Data System (ADS)

Ortiz-Rivera, Isamar

Non-mechanical nano and microfluidic devices that function without the aid of an external power source, and can be tailored to meet specific needs, represent the next generation of smart devices. Recently, we have shown that surface-bound enzymes can act as pumps driving large-scale fluid flows in the presence of any substance that triggers the enzymatic reaction (e.g. substrate, co-factor, or biomarker). The fluid velocities attained in such systems depend directly on the enzymatic reaction rate and the concentration of the substance that initiates enzymatic catalysis. The use of biochemical reactions to power a micropump offers the advantages of specificity, sensitivity, and selectively, eliminating at the same time the need of an external power source, while providing biocompatibility. More importantly, these self-powered pumps overcome a significant obstacle in nano- and micro-fluidics: the need to use external pressure-driven pumps to push fluids through devices. Certainly, the development of enzyme-powered devices opens up new venues in biochemical engineering, particularly in the biomedical field. The work highlighted in this dissertation covers all the studies performed with enzyme-powered pumps, from the development of the micropump design, to the efforts invested in understanding the enzyme pump concept as a whole. The data collected to date, aims to expand our knowledge about enzyme-powered micropumps from the inside out: not only by exploring the different applications of these devices at the macroscale, but also by investigating in depth the mechanism of pump activation behind these systems. Specifically, we have focused on: (1) The general features that characterize the pumping behavior observed in enzyme-powered pumps, as well as the optimization of the device, (2) the possible mechanisms behind fluid motion, including the role of enzyme coverage and/or activity on the transduction of chemical energy into mechanical fluid flow in these devices, covering also the effect of the thermodynamics of the enzymatic reaction in the pumping behavior, and (3) the applicability of enzyme pumps as fluid flow-based inhibitor assays and as drug delivery devices. Our findings in each of these areas, gets us closer to our ultimate goal, where we aim to identify the optimal conditions needed for enzyme micropump operation, and construct a general model that could accurately predict enzyme micropump behavior for any enzyme-substrate combination. The information aforementioned has been divided in four chapters. Chapter 1 gives a quick glance into the development of enzyme-powered micropumps: from the systems and observed behaviors inspiring this work, to the first systems that were developed. The stability, duration, and extent of fluid pumping of enzyme pumps in general, are also discussed, along with the optimization of the enzyme-pump design. This chapter aims to provide a general idea of the motivation behind the concept of "enzyme-powered pumps", what are "enzyme-powered pumps", and which are the key features that characterize these systems. Chapter 2 is an extensive analysis of the mechanisms of actuation proposed for enzyme-powered micropumps. This chapter not only covers the first attempts to understand how enzyme pumps work, but also explores further the behavior of urease-powered pumps, which fluid flow patterns cannot be completely predicted only by considering thermal or solutal gradients. The findings of these studies could allow us to rationally control fluid flow for the directed delivery of payloads at designated locations. In Chapters 3 and 4, our focus was to highlight the potential application of enzyme-powered pumps for sensing and delivery. Chapter 3 explores the use of enzyme pumps as fluid flow-based inhibitor assays. At fixed concentrations of an enzyme and its substrate, the presence of an inhibitor can be detected by monitoring the decrease in fluid flow speed. Using this principle, sensors for toxic substances, like mercury, cyanide and azide, were designed using urease and catalase-powered pumps, respectively, with limits of detection well below the concentrations permitted by the Environmental Protection Agency (EPA). Chapter 4 demonstrates that, apart from their applicability as sensors, enzyme pumps can also be used for stimuli-responsive release, if the architecture applied for the design of the enzyme pump consists of a porous scaffold (e.g. hydrogel), that serves both as the platform for enzyme immobilization and as the host for guest molecules to be released. These proof-of-concept devices were developed with the idea of using the flows generated by enzymatic catalysis to power cargo release, only in the presence of the correct stimuli (e.g. release of insulin in the presence of glucose; release of antidotes in the presence of a toxic agent). In the cases studied, cargo release was directly proportional to the concentration of enzyme substrate in solution, highlighting the sensitivity of the device and its potential for drug delivery purposes. (Abstract shortened by Proquest.).

Microencapsulation of Drugs: New Cancer Therapies and Improved Drug Delivery Derived from Micro Gravity Research

NASA Technical Reports Server (NTRS)

Morrison, Dennis R.; Haddad, Ruwaida S.

2003-01-01

Experiments on the ISS include encapsulation of several different anti-cancer drugs, magnetic triggering particles, and encapsulation of genetically engineered DNA. Eight experiments, using the MEPS-II apparatus, were conducted to study the limitations of the fluid shear and g-dependent forces. These studies included: 1) formation of anti-tumor microcapsules containing drugs for "Chemoembolization" of vascularized tumors, 2) formation of microcapsules containing a photo-activated drug which can be used for Photo Dynamic Therapy of solid tumors by activation with near infrared light (630 nm), 3) coencapsulation of magnetic trigger particles and anti-tumor drugs, and 4) encapsulation of plasmid DNA. The Microencapsulation Electrostatic Processing System (MEPS-II) is an automated apparatus modified for use in the ISS Express Rack. The process brings together two immiscible liquids, restricting fluid shear to permitting surface tension forces to predominate at the interface of the fluids. Microcapsules were recovered from all 8 experiments and are currently being analyzed for size distribution and drug content. Six NASA Patents have issued from the space research and several more are pending. The preliminary results from the Increment 5 - UF-2 experiments have provided new insight into the best formulations and conditions required to produce microcapsules of different drugs, esp. special capsules containing diagnostic imaging materials and triggered release particles. Co-encapsulation of multiple drugs and Photodynamic Therapy (PDT) drugs has enabled new engineering strategies for production of microcapsules on Earth designed for direct delivery into cancer tissues. Other microcapsules have now been made for treatment of deep tissue infections, clotting disorders, and to provide delivery of genetic engineered materials for potential gene therapy approaches. The MEPS-II apparatus remains in the ISS awaiting microencapsulation experiments to be conducted in micro-g, and returned to Earth for analysis.

A microfluidic reciprocating intracochlear drug delivery system with reservoir and active dose control

PubMed Central

Kim, Ernest S.; Gustenhoven, Erich; Mescher, Mark J.; Pararas, Erin E. Leary; Smith, Kim A.; Spencer, Abigail J.; Tandon, Vishal; Borenstein, Jeffrey T.; Fiering, Jason

2014-01-01

Reciprocating microfluidic drug delivery, as compared to steady or pulsed infusion, has unique features which may be advantageous in many therapeutic applications. We have previously described a device, designed for wearable use in small animal models, which periodically infuses then withdraws a sub-microliter volume of drug solution to and from the endogenous fluid of the inner ear. This delivery approach results in zero net volume of liquid transfer while enabling mass transport of compounds to the cochlea by means of diffusion and mixing. We report here on an advanced wearable delivery system aimed at further miniaturization and complex dose protocols. Enhancements to the system include the incorporation of a planar micropump to generate reciprocating flow and a novel drug reservoir which maintains zero net volume delivery and permits programmable modulation of the drug concentration in the infused bolus. The reciprocating pump is fabricated from laminated polymer films and employs a miniature electromagnetic actuator to meet the size and weight requirements of a head-mounted in vivo guinea pig testing system. The reservoir comprises a long microchannel in series with a micropump, connected in parallel with the reciprocating flow network. We characterized in vitro the response and repeatability of the planar pump and compared the results with a lumped element simulation. We also characterized the performance of the reservoir, including repeatability of dosing and range of dose modulation. Acute in vivo experiments were performed in which the reciprocating pump was used to deliver a test compound to the cochlea of anesthetized guinea pigs to evaluate short-term safety and efficacy of the system. These advances are key steps toward realization of an implantable device for long-term therapeutic applications in humans. PMID:24302432

The Stability and Oxidation Resistance of Iron- and Cobalt-Based Magnetic Nanoparticle Fluids Fabricated by Inert-Gas Condensation

DTIC Science & Technology

2005-01-01

imaging, drug delivery, and hyperthermia treatment for cancer . Ideal magnetic nanoparticle fluids have well-separated, biocompatible nanoparticles with a...Based Magnetic Nanoparticle Fluids Fabricated by Inert-Gas Condensation DISTRIBUTION: Approved for public release, distribution unlimited This paper...Oxidation Resistance of Iron- and Cobalt-Based Magnetic Nanoparticle Fluids Fabricated by Inert-Gas Condensation Nguyen H. Hail, Raymond Lemoine’, Shaina

The effects of delivery route and anesthesia type on early postnatal weight loss in newborns: the role of vasoactive hormones.

PubMed

Okumus, Nurullah; Atalay, Yildiz; Onal, Eray E; Turkyilmaz, Canan; Senel, Saliha; Gunaydin, Berrin; Pasaoglu, Hatice; Koc, Esin; Ergenekon, Ebru; Unal, Suna

2011-01-01

To investigate the effects of delivery route and maternal anesthesia type and the roles of vasoactive hormones on early postnatal weight loss in term newborns. Ninety-four term infants delivered vaginally (group 1, n=31), cesarean section (C/S) with general anesthesia (GA) (group 2, n=29), and C/S with epidural anesthesia (EA) (group 3, n=34) were included in this study. All infants were weighed at birth and on the second day of life and intravenous (IV) fluid infused to the mothers for the last 6 h prior to delivery was recorded. Serum electrolytes, osmolality, N-terminal proANP (NT-proANP), brain natriuretic peptide (BNP), aldosterone and plasma antidiuretic hormone (ADH) concentrations were measured at cord blood and on the second day of life. Our research showed that postnatal weight loss of infants was higher in C/S than vaginal deliveries (5.7% vs. 1.3%) (p < 0.0001) and in EA group than GA group (6.8% vs. 4.3%) (p < 0.0001). Postnatal weight losses were correlated with IV fluid volume infused to the mothers for the last 6 h prior to delivery (R = 0.814, p = 0.000) and with serum NT-proANP (R = 0.418, p = 0.000), BNP (R = 0.454, p = 0.000), and ADH (R = 0.509, p = 0.000) but not with aldosterone concentrations (p > 0.05). Large amounts of IV fluid given to the mothers who were applied EA prior to the delivery affect their offsprings' postnatal weight loss via certain vasoactive hormones.

Molten salt destruction of energetic waste materials

DOEpatents

Brummond, W.A.; Upadhye, R.S.; Pruneda, C.O.

1995-07-18

A molten salt destruction process is used to treat and destroy energetic waste materials such as high explosives, propellants, and rocket fuels. The energetic material is pre-blended with a solid or fluid diluent in safe proportions to form a fluid fuel mixture. The fuel mixture is rapidly introduced into a high temperature molten salt bath. A stream of molten salt is removed from the vessel and may be recycled as diluent. Additionally, the molten salt stream may be pumped from the reactor, circulated outside the reactor for further processing, and delivered back into the reactor or cooled and circulated to the feed delivery system to further dilute the fuel mixture entering the reactor. 4 figs.

Molten salt destruction of energetic waste materials

DOEpatents

Brummond, William A.; Upadhye, Ravindra S.; Pruneda, Cesar O.

1995-01-01

A molten salt destruction process is used to treat and destroy energetic waste materials such as high explosives, propellants, and rocket fuels. The energetic material is pre-blended with a solid or fluid diluent in safe proportions to form a fluid fuel mixture. The fuel mixture is rapidly introduced into a high temperature molten salt bath. A stream of molten salt is removed from the vessel and may be recycled as diluent. Additionally, the molten salt stream may be pumped from the reactor, circulated outside the reactor for further processing, and delivered back into the reactor or cooled and circulated to the feed delivery system to further dilute the fuel mixture entering the reactor.

Isothermal pumping analysis for high-altitude tethered balloons

PubMed Central

Kuo, Kirsty A.; Hunt, Hugh E. M.

2015-01-01

High-altitude tethered balloons have potential applications in communications, surveillance, meteorological observations and climate engineering. To maintain balloon buoyancy, power fuel cells and perturb atmospheric conditions, fluids could be pumped from ground level to altitude using the tether as a hose. This paper examines the pumping requirements of such a delivery system. Cases considered include delivery of hydrogen, sulfur dioxide (SO2) and powders as fluid-based slurries. Isothermal analysis is used to determine the variation of pressures and velocities along the pipe length. Results show that transport of small quantities of hydrogen to power fuel cells and maintain balloon buoyancy can be achieved at pressures and temperatures that are tolerable in terms of both the pipe strength and the current state of pumping technologies. To avoid solidification, transport of SO2 would require elevated temperatures that cannot be tolerated by the strength fibres in the pipe. While the use of particle-based slurries rather than SO2 for climate engineering can reduce the pipe size significantly, the pumping pressures are close to the maximum bursting pressure of the pipe. PMID:26543573

Isothermal pumping analysis for high-altitude tethered balloons.

PubMed

Kuo, Kirsty A; Hunt, Hugh E M

2015-06-01

High-altitude tethered balloons have potential applications in communications, surveillance, meteorological observations and climate engineering. To maintain balloon buoyancy, power fuel cells and perturb atmospheric conditions, fluids could be pumped from ground level to altitude using the tether as a hose. This paper examines the pumping requirements of such a delivery system. Cases considered include delivery of hydrogen, sulfur dioxide (SO2) and powders as fluid-based slurries. Isothermal analysis is used to determine the variation of pressures and velocities along the pipe length. Results show that transport of small quantities of hydrogen to power fuel cells and maintain balloon buoyancy can be achieved at pressures and temperatures that are tolerable in terms of both the pipe strength and the current state of pumping technologies. To avoid solidification, transport of SO2 would require elevated temperatures that cannot be tolerated by the strength fibres in the pipe. While the use of particle-based slurries rather than SO2 for climate engineering can reduce the pipe size significantly, the pumping pressures are close to the maximum bursting pressure of the pipe.

Examining Dehydration and Hypoxic Stress in Wheat Plants Using a Porous Tube Plant Nutrient Delivery System Developed for Microgravity

NASA Technical Reports Server (NTRS)

Dreschel, T. W.; Hall, C. R.; Foster, T. E.; Salganic, M.; Warren, L.; Corbett, M.

2005-01-01

The Porous Tube Plant Nutrient Delivery System (PTPNDS) was designed for NASA to grow plants in microgravity of space. The system utilizes a controlled fluid loop to supply nutrients and water to plant roots growing on a ceramic surface moistened by capiflary action. A PTPNDS test bed was developed and utilizing remote sensing systems, spectral analyses procedures, gas-exchange, and fluorescence measurements, we examined differences in plant water status for wheat plants (Triticum aestivum, cv. Perigee) grown in a modified growth chamber during the summers of 2003 and 2004. Some differences in plant performance were detectable in the gas-exchange and fluorescence measurements. For instance, in both years the plants grown with the most available water had the lowest rates of photosynthesis and exhibited higher proportions of non-photochemical quenching particularly under low light levels. In addition, small differences in mean leaf water content between treatments were detected using spectral reflectance analyses.

Subxyphoid access of the normal pericardium: a novel drug delivery technique.

PubMed

Laham, R J; Simons, M; Hung, D

1999-05-01

The pericardial space may potentially serve as a drug delivery reservoir that might be used to deliver therapeutic substances to the heart. This study describes a novel delivery technique that enables safe and rapid percutaneous subxyphoid access of the normal pericardium in a large animal model (49 Yorkshire pigs). An epidural introducer needle (Tuohy-17) is advanced gently under fluoroscopic guidance with a continuous positive pressure of 20-30 mm Hg (achieved by saline infusion using an intraflow system). The positive pressure is intended to push the right ventricle (with a lower pressure) away from the needle's path. Entry of the pericardial space is suspected after an increase in the saline flow through the intraflow system. Access to the pericardial space is confirmed by the injection of 1 ml of diluted contrast under fluoroscopy. A soft floppy-tip 0.025" guidewire is then advanced to the pericardial space and the needle is exchanged for an infusion catheter. Access of the pericardial space was achieved in all animals without any adverse events and without any hemodynamic compromise even with the delivery of fluid volumes as large as 50 ml. Histologic examination in 15 animals 4 weeks after pericardial access did not reveal any delivery-related myocardial damage. The safety, ease, and absence of hemodynamic compromise make this technique a potentially useful method for intrapericardial drug delivery and a good alternative to standard pericardiocentesis in patients with small pericardial effusions at higher risk for complications.

Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

PubMed Central

Ita, Kevin

2015-01-01

Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use. PMID:26131647

MRI-Based Computational Model of Heterogeneous Tracer Transport following Local Infusion into a Mouse Hind Limb Tumor

PubMed Central

Magdoom, Kulam Najmudeen; Pishko, Gregory L.; Rice, Lori; Pampo, Chris; Siemann, Dietmar W.; Sarntinoranont, Malisa

2014-01-01

Systemic drug delivery to solid tumors involving macromolecular therapeutic agents is challenging for many reasons. Amongst them is their chaotic microvasculature which often leads to inadequate and uneven uptake of the drug. Localized drug delivery can circumvent such obstacles and convection-enhanced delivery (CED) - controlled infusion of the drug directly into the tissue - has emerged as a promising delivery method for distributing macromolecules over larger tissue volumes. In this study, a three-dimensional MR image-based computational porous media transport model accounting for realistic anatomical geometry and tumor leakiness was developed for predicting the interstitial flow field and distribution of albumin tracer following CED into the hind-limb tumor (KHT sarcoma) in a mouse. Sensitivity of the model to changes in infusion flow rate, catheter placement and tissue hydraulic conductivity were investigated. The model predictions suggest that 1) tracer distribution is asymmetric due to heterogeneous porosity; 2) tracer distribution volume varies linearly with infusion volume within the whole leg, and exponentially within the tumor reaching a maximum steady-state value; 3) infusion at the center of the tumor with high flow rates leads to maximum tracer coverage in the tumor with minimal leakage outside; and 4) increasing the tissue hydraulic conductivity lowers the tumor interstitial fluid pressure and decreases the tracer distribution volume within the whole leg and tumor. The model thus predicts that the interstitial fluid flow and drug transport is sensitive to porosity and changes in extracellular space. This image-based model thus serves as a potential tool for exploring the effects of transport heterogeneity in tumors. PMID:24619021

Dynamic Contrast-Enhanced MRI of Gd-albumin Delivery to the Rat Hippocampus In Vivo by Convection-Enhanced Delivery

PubMed Central

Kim, Jung Hwan; Astary, Garrett W.; Nobrega, Tatiana L.; Kantorovich, Svetlana; Carney, Paul R.; Mareci, Thomas H.; Sarntinoranont, Malisa

2013-01-01

Convection enhanced delivery (CED) shows promise in treating neurological diseases due to its ability to circumvent the blood-brain barrier (BBB) and deliver therapeutics directly to the parenchyma of the central nervous system (CNS). Such a drug delivery method may be useful in treating CNS disorders involving the hippocampus such temporal lobe epilepsy and gliomas; however, the influence of anatomical structures on infusate distribution is not fully understood. As a surrogate for therapeutic agents, we used gadolinium-labeled-albumin (Gd-albumin) tagged with Evans blue dye to observe the time dependence of CED infusate distributions into the rat dorsal and ventral hippocampus in vivo with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). For finer anatomical detail, final distribution volumes (Vd) of the infusate were observed with high-resolution T1-weighted MR imaging and light microscopy of fixed brain sections. Dynamic images demonstrated that Gd-albumin preferentially distributed within the hippocampus along neuroanatomical structures with less fluid resistance and less penetration was observed in dense cell layers. Furthermore, significant leakage into adjacent cerebrospinal fluid (CSF) spaces such as the hippocampal fissure, velum interpositum and midbrain cistern occurred toward the end of infusion. Vd increased linearly with infusion volume (Vi) at a mean Vd/Vi ratio of 5.51 ± 0.55 for the dorsal hippocampus infusion and 5.30 ± 0.83 for the ventral hippocampus infusion. This study demonstrated the significant effects of tissue structure and CSF space boundaries on infusate distribution during CED. PMID:22687936

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

Thick-tissue bioreactor as a platform for long-term organotypic culture and drug delivery.

PubMed

Markov, Dmitry A; Lu, Jenny Q; Samson, Philip C; Wikswo, John P; McCawley, Lisa J

2012-11-07

We have developed a novel, portable, gravity-fed, microfluidics-based platform suitable for optical interrogation of long-term organotypic cell culture. This system is designed to provide convenient control of cell maintenance, nutrients, and experimental reagent delivery to tissue-like cell densities housed in a transparent, low-volume microenvironment. To demonstrate the ability of our Thick-Tissue Bioreactor (TTB) to provide stable, long-term maintenance of high-density cellular arrays, we observed the morphogenic growth of human mammary epithelial cell lines, MCF-10A and their invasive variants, cultured under three-dimensional (3D) conditions inside our system. Over the course of 21 days, these cells typically develop into hollow "mammospheres" if cultured in standard 3D Matrigel. This complex morphogenic process requires alterations in a variety of cellular functions, including degradation of extracellular matrix that is regulated by cell-produced matrix proteinases. For our "drug" delivery testing and validation experiments we have introduced proteinase inhibitors into the fluid supply system, and we observed both reduced proteinase activity and inhibited cellular morphogenesis. The size inhibition results correlated well with the overall proteinase activities of the tested cells.

Design and evaluation of hydrophobic coated buoyant core as floating drug delivery system for sustained release of cisapride

PubMed Central

Jacob, Shery; Nair, Anroop B; Patil, Pandurang N

2010-01-01

An inert hydrophobic buoyant coated–core was developed as floating drug delivery system (FDDS) for sustained release of cisapride using direct compression technology. Core contained low density, porous ethyl cellulose, which was coated with an impermeable, insoluble hydrophobic coating polymer such as rosin. It was further seal coated with low viscosity hydroxypropyl methyl cellulose (HPMC E15) to minimize moisture permeation and better adhesion with an outer drug layer. It was found that stable buoyant core was sufficient to float the tablet more than 8 h without the aid of sodium bicarbonate and citric acid. Sustained release of cisapride was achieved with HPMC K4M in the outer drug layer. The floating lag time required for these novel FDDS was found to be zero, however it is likely that the porosity or density of the core is critical for floatability of these tablets. The in vitro release pattern of these tablets in simulated gastric fluid showed the constant and controlled release for prolonged time. It can be concluded that the hydrophobic coated buoyant core could be used as FDDS for gastroretentive delivery system of cisapride or other suitable drugs. PMID:24825997

Efficient CNS targeting in adult mice by intrathecal infusion of single-stranded AAV9-GFP for gene therapy of neurological disorders.

PubMed

Bey, K; Ciron, C; Dubreil, L; Deniaud, J; Ledevin, M; Cristini, J; Blouin, V; Aubourg, P; Colle, M-A

2017-05-01

Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the treatment of neurodegenerative diseases. While AAVs are generally administered systemically to newborns in preclinical studies of neurological disorders, in adults the maturity of the blood-brain barrier (BBB) must be considered when selecting the route of administration. Delivery of AAVs into the cerebrospinal fluid (CSF) represents an attractive approach to target the central nervous system (CNS) and bypass the BBB. In this study, we investigated the efficacy of intra-CSF delivery of a single-stranded (ss) AAV9-CAG-GFP vector in adult mice via intracisternal (iCist) or intralumbar (it-Lumb) administration. It-Lumb ssAAV9 delivery resulted in greater diffusion throughout the entire spinal cord and green fluorescent protein (GFP) expression mainly in the cerebellum, cortex and olfactory bulb. By contrast, iCist delivery led to strong GFP expression throughout the entire brain. Comparison of the transduction efficiency of ssAAV9-CAG-GFP versus ssAAV9-SYN1-GFP following it-Lumb administration revealed widespread and specific GFP expression in neurons and motoneurons of the spinal cord and brain when the neuron-specific synapsin 1 (SYN1) promoter was used. Our findings demonstrate that it-Lumb ssAAV9 delivery is a safe and highly efficient means of targeting the CNS in adult mice.

The Clinical Significance of Eosinophils in the Amniotic Fluid in Preterm Labor

PubMed Central

ROMERO, ROBERTO; KUSANOVIC, JUAN PEDRO; GOMEZ, RICARDO; LAMONT, RONALD; BYTAUTIENE, EGLE; GARFIELD, ROBERT E.; MITTAL, POOJA; HASSAN, SONIA S.; YEO, LAMI

2012-01-01

Objective White blood cells are not traditionally considered to be normally present in amniotic fluid. This study was conducted after the observation that a patient with preterm labor and intact membranes had eosinophils as a predominant cell in the amniotic fluid, and had an episode of asthma during the index pregnancy. The goal of this study was to determine whether women presenting with preterm labor with eosinophils in the amniotic fluid had a different outcome than those without eosinophils as the predominant white blood cell in the amniotic cavity. Methods This retrospective case-control study included women who presented with preterm labor and intact membranes between 24 and 34 weeks of gestation. Patients underwent an amniocentesis shortly after admission for the assessment of the microbiologic status of the amniotic cavity and/or fetal lung maturity. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Cytologic studies included amniotic fluid white blood cell count and differential, which was performed on cytocentrifuged specimens. Patients with microbial invasion of the amniotic cavity and/or a white blood cell count >20 cells/mm3 were excluded from the study. Cases were defined as women in whom the differential contained >20% of eosinophils. Controls were selected among women with an amniotic fluid eosinophil count ≤20% and matched for gestational age at amniocentesis. The analysis was conducted with non-parametric statistics. Results The study population consisted of 10 cases and 50 controls. Gestational age and cervical dilatation at admission were similar in both groups. Cases had a lower gestational age at delivery than controls [34.6 weeks, inter-quartile range (IQR) 32–37.3 weeks vs. 38.0 weeks, IQR 35–40 weeks, respectively; p=0.018]. The prevalence of preterm delivery ≤35 weeks was higher among patients who had >20% eosinophils than in the control group [50% (5/10) vs. 18% (9/50), respectively; p=0.029]. Similar results were observed for delivery at <37 weeks [Cases: 70% (7/10) vs. Controls: 36% (18/50); p=0.046]. Conclusions Women with preterm labor and intact membranes who have a large proportion of eosinophils in the amniotic fluid are at an increased risk for spontaneous preterm delivery. These patients may have had an episode of preterm labor related to a type I hypersensitivity reaction. PMID:19900034

Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery.

PubMed

Jing, Zi-Wei; Ma, Zhi-Wei; Li, Chen; Jia, Yi-Yang; Luo, Min; Ma, Xi-Xi; Zhou, Si-Yuan; Zhang, Bang-Le

2017-02-15

The covalently cross-linked chitosan-poly(ethylene glycol) 1540 derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG 1540 -dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12h. The results proved that the release-and-hold behavior of the cross-linked CS-PEG 1540 H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of Nano Bamboo Charcoal Drug Delivery System for Eucommia ulmoides Extract and Its Anticancer Effect In vitro.

PubMed

Zeng, Zhaoyan; Li, Xiangzhou; Zhang, Sheng; Huang, Dan

2017-01-01

Nano bamboo charcoal is being widely used as sustained release carrier for chemicals for its high specific surface area, sound biocompatibility, and nontoxicity; however, there have been no reports on nano bamboo charcoal as sustained release carrier for traditional Chinese medicine (TCM). To study the effect of nano bamboo charcoal in absorbing and sustained releasing Eucommia ulmoides extract (EUE) and to verify the in vitro anticancer effect of the sustained release liquid, so as to provide a theoretical basis for the development and utilization of nano bamboo charcoal as TCM sustained-release preparation. The adsorption capacity for the nano bamboo charcoal on EUE was measured by Langmuir model, and the release experiment was carried out under intestinal fluid condition. Characteristic changes for the nano bamboo charcoal nano-drug delivery system with and without adsorption of E. ulmoides were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and specific surface area. In addition, the anticancer effect from this novel bamboo charcoal E. ulmoides delivery system was evaluated against a human colon cancer cell line (HCT116). It was found that nano bamboo charcoal exhibits good adsorption capacity (up to 462.96 mg/g at 37°C). The cumulative release rate for EUE from this nano bamboo charcoal delivery system was 70.67%, and specific surface area for the nano bamboo charcoal decreased from 820.32 m 2 /g to 443.80 m 2 /g after EUE was loaded. An in vitro anticancer study showed that the inhibition rate for E. ulmoides against HCT116 cancer cells was 23.07%, for this novel bamboo charcoal nano-drug delivery system. This study provides a novel strategy for the delivery of traditional Chinese medicine using bamboo charcoal nano-drug delivery system. The adsorption equilibrium was reached after 30 min of ultrasonic treatmentThe saturated adsorption capacity of Eucommia ulmoides extract by nano bamboo charcoal under ultrosonic condition was 462. 96 mg/gThe cumulative release rate of E. ulmoides extract from the nano bamboo charcoal delivery system in artificial intestinal juice was 70.67%The inhibition ratio of HCT116 cancer cells by sustained release liquid was 23.07%. Abbreviation used: EUE: Eucommia ulmoides extract.

The Sheep as a Model of Preclinical Safety and Pharmacokinetic Evaluations of Candidate Microbicides

PubMed Central

Cameron, David; Dias, Nicola; Holding, Jeremy; Muntendam, Alex; Oostebring, Freddy; Dreier, Peter; Rohan, Lisa; Nuttall, Jeremy

2015-01-01

When developing novel microbicide products for the prevention of HIV infection, the preclinical safety program must evaluate not only the active pharmaceutical ingredient but also the product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an assessment of the pharmacokinetics, safety, tolerability, and local toxicity of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal Ring-004). We performed a 3-month general toxicology study, a preliminary pharmacokinetic study using drug-loaded vaginal gel, and a detailed assessment of the kinetics of dapivirine delivery to plasma, vaginal, and rectal fluid and rectal, vaginal, and cervical tissue over 28 days of exposure and 3 and 7 days after removal of the ring. The findings of the general toxicology study supported the existing data from both preclinical and clinical studies in that there were no signs of toxicity related to dapivirine. In addition, the presence of the physical dapivirine ring did not alter local or systemic toxicity or the pharmacokinetics of dapivirine. Pharmacokinetic studies indicated that the dapivirine ring produced significant vaginal tissue levels of dapivirine. However, no dapivirine was detected in cervical tissue samples using the methods described here. Plasma and vaginal fluid levels were lower than those in previous clinical studies, while there were detectable dapivirine levels in the rectal tissue and fluid. All tissue and fluid levels tailed off rapidly to undetectable levels following removal of the ring. The sheep represents a very useful model for the assessment of the safety and pharmacokinetics of microbicide drug delivery devices, such as the vaginal ring. PMID:25845860

Intrascleral Drug Delivery to the Eye Using Hollow Microneedles

PubMed Central

Jiang, Jason; Moore, Jason S.; Edelhauser, Henry F.; Prausnitz, Mark R.

2010-01-01

Purpose This study tested the hypothesis that hollow microneedles can infuse solutions containing soluble molecules, nanoparticles, and microparticles into sclera in a minimally invasive manner. Methods Individual hollow microneedles were inserted into, but not across, human cadaver sclera and aqueous solutions containing sulforhodamine or fluorescently-tagged nanoparticles or microparticles were infused into sclera at constant pressure. The infused volume of fluid was measured and imaged histologically as a function of scleral thickness, infusion pressure, needle retraction depth and the presence of spreading enzymes (hyaluronidase and collagenase). Results Individual hollow microneedles were able to insert into sclera. Fluid infusion was extremely slow after microneedle insertion into the sclera without retraction, but partial retraction of the microneedle over a distance of 200–300 μm enabled infusion of 10–35 μl of fluid into the tissue. Scleral thickness and infusion pressure had insignificant effects on fluid delivery. Nanoparticle suspensions were also delivered into sclera, but microparticles were delivered only in the presence of hyaluronidase and collagenase spreading enzymes, which suggested the role of scleral glycosaminoglycans and collagen fibers as rate-limiting barriers. Conclusion This study shows that hollow microneedles can infuse solutions into the sclera for minimally invasive delivery of soluble molecules, nanoparticles and microparticles. PMID:18979189

Drug transport across the blood–brain barrier

PubMed Central

Pardridge, William M

2012-01-01

The blood–brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. This property arises from the epithelial-like tight junctions within the brain capillary endothelium. The BBB is anatomically and functionally distinct from the blood–cerebrospinal fluid barrier at the choroid plexus. Certain small molecule drugs may cross the BBB via lipid-mediated free diffusion, providing the drug has a molecular weight <400 Da and forms <8 hydrogen bonds. These chemical properties are lacking in the majority of small molecule drugs, and all large molecule drugs. Nevertheless, drugs can be reengineered for BBB transport, based on the knowledge of the endogenous transport systems within the BBB. Small molecule drugs can be synthesized that access carrier-mediated transport (CMT) systems within the BBB. Large molecule drugs can be reengineered with molecular Trojan horse delivery systems to access receptor-mediated transport (RMT) systems within the BBB. Peptide and antisense radiopharmaceuticals are made brain-penetrating with the combined use of RMT-based delivery systems and avidin–biotin technology. Knowledge on the endogenous CMT and RMT systems expressed at the BBB enable new solutions to the problem of BBB drug transport. PMID:22929442

4D ERT-based calibration and prediction of biostimulant induced changes in fluid conductivity

NASA Astrophysics Data System (ADS)

Johnson, T. C.; Versteeg, R. J.; Day-Lewis, F. D.; Major, W. R.; Wright, K. E.

2008-12-01

In-situ bioremediation is an emerging and cost-effective method of removing organic contaminants from groundwater. The performance of bioremedial systems depends on the adequate delivery and distribution of biostimulants to contaminated zones. Monitoring the distribution of biostimulants using monitoring wells is expensive, time consuming, and provides inadequate information between sampling wells. We discuss a Hydrogeophysical Performance Monitoring System (HPMS) deployed to monitor bioremediation efforts at a TCE-contaminated Superfund site in Brandywine MD. The HPMS enables autonomous electrical geophysical data acquisition, processing, quality-assurance/quality-control, and inversion. Our objective is to demonstrate the feasibility and cost effectiveness of the HPMS to provide near real-time information on the spatiotemporal behavior of injected biostimulants. As a first step, we use time-lapse electrical resistivity tomography (ERT) to estimate changes in bulk conductivity caused by the injectate. We demonstrate how ERT-based bulk conductivity estimates can be calibrated with a small number of fluid conductivity measurements to produce ERT-based estimates of fluid conductivity. The calibration procedure addresses the spatially variable resolution of the ERT tomograms. To test the validity of these estimates, we used the ERT results to predict the fluid conductivity at tens of points prior to field sampling of fluid conductivity at the same points. The comparison of ERT-predicted vs. observed fluid conductivity displays a high degree of correlation (correlation coefficient over 0.8), and demonstrates the ability of the HPMS to estimate the four-dimensional (4D) distribution of fluid conductivity caused by the biostimulant injection.

Amnioinfusion in term labor with low amniotic fluid due to rupture of membranes: a new indication.

PubMed

Miño, M; Puertas, A; Miranda, J A; Herruzo, A J

1999-01-01

The null hypothesis was that the use of intrapartum amnioinfusion to induce term labor because of premature rupture of membranes when labor was complicated by low amniotic fluid volume due to vaginal loss would not improve fetal heart rate patterns, decrease the incidence of operative delivery, or improve neonatal acid-base status. 200 term pregnancies with low amniotic fluid due to vaginal loss were randomly chosen to receive intrapartum amnioinfusion or standard obstetric care without amnioinfusion. Fetal heart rate pattern, method of delivery and neonatal acid-base status were compared with Student's t test, chi-squared analysis, Mann-Whitney U- or Fisher's exact test. When amnioinfusion was used, the fetuses had lower rates of variable (74 vs. 91%, P<0.01) or late (26 vs. 58%, P<0.001) decelerations. Spontaneous deliveries were more frequent (77 vs. 59%, P<0.01) and cesarean sections less frequent (3 vs. 10%, P<0.05). Mean umbilical arterial (7.24+/-0.07 vs. 7.21+/-0.08, P<0.01) and venous (7.31+/-0.06 vs. 7.28+/-0.08, P<0.01) pH were significantly higher in newborns with amnioinfusion, and babies in this group had lower rates of neonatal acidemia of arterial (22 vs. 36%, P<0.005) or venous (13 vs. 26%, P<0.005) origin. Amnioinfusion improved fetal heart rate pattern, lowered the incidence of operative delivery, and improved neonatal acid-base status in term labor complicated by low amniotic fluid due to vaginal loss.

Transient swelling, spreading, and drug delivery by a dissolved anti-HIV microbicide-bearing film

NASA Astrophysics Data System (ADS)

Tasoglu, Savas; Rohan, Lisa C.; Katz, David F.; Szeri, Andrew J.

2013-03-01

There is a widespread agreement that more effective drug delivery vehicles with more alternatives, as well as better active pharmaceutical ingredients (APIs), must be developed to improve the efficacy of microbicide products. For instance, in tropical regions, films are more appropriate than gels due to better stability of drugs at extremes of moisture and temperature. Here, we apply fundamental fluid mechanical and physicochemical transport theory to help better understand how successful microbicide API delivery depends upon properties of a film and the human reproductive tract environment. Several critical components of successful drug delivery are addressed. Among these are: elastohydrodynamic flow of a dissolved non-Newtonian film; mass transfer due to inhomogeneous dilution of the film by vaginal fluid contacting it along a moving boundary (the locally deforming vaginal epithelial surface); and drug absorption by the epithelium. Local rheological properties of the film are dependent on local volume fraction of the vaginal fluid. We evaluated this experimentally, delineating the way that constitutive parameters of a shear-thinning dissolved film are modified by dilution. To develop the mathematical model, we integrate the Reynolds lubrication equation with a mass conservation equation to model diluting fluid movement across the moving vaginal epithelial surface and into the film. This is a complex physicochemical phenomenon that is not well understood. We explore time- and space-varying boundary flux model based upon osmotic gradients. Results show that the model produces fluxes that are comparable to experimental data. Further experimental characterization of the vaginal wall is required for a more precise set of parameters and a more sophisticated theoretical treatment of epithelium.

Chemically generated convective transport in microfluidic system

NASA Astrophysics Data System (ADS)

Shklyaev, Oleg; Das, Sambeeta; Altemose, Alicia; Shum, Henry; Balazs, Anna; Sen, Ayusman

High precision manipulation of small volumes of fluid, containing suspended micron sized objects like cells, viruses, and large molecules, is one of the main goals in designing modern lab-on-a-chip devices which can find a variety of chemical and biological applications. To transport the cargo toward sensing elements, typical microfluidic devices often use pressure driven flows. Here, we propose to use enzymatic chemical reactions which decompose reagent into less dense products and generate flows that can transport particles. Density variations that lead to flow in the assigned direction are created between the place where reagent is fed into the solution and the location where it is decomposed by enzymes attached to the surface of the microchannel. When the reagent is depleted, the fluid motion stops and particles sediment to the bottom. We demonstrate how the choice of chemicals, leading to specific reaction rates, can affect the transport properties. In particular, we show that the intensity of the fluid flow, the final location of cargo, and the time for cargo delivery are controlled by the amount and type of reagent in the system.

Hybrid Method for Power Control Simulation of a Single Fluid Plasma Thruster

NASA Astrophysics Data System (ADS)

Jaisankar, S.; Sheshadri, T. S.

2018-05-01

Propulsive plasma flow through a cylindrical-conical diverging thruster is simulated by a power controlled hybrid method to obtain the basic flow, thermodynamic and electromagnetic variables. Simulation is based on a single fluid model with electromagnetics being described by the equations of potential Poisson, Maxwell and the Ohm's law while the compressible fluid dynamics by the Navier Stokes in cylindrical form. The proposed method solved the electromagnetics and fluid dynamics separately, both to segregate the two prominent scales for an efficient computation and for the delivery of voltage controlled rated power. The magnetic transport is solved for steady state while fluid dynamics is allowed to evolve in time along with an electromagnetic source using schemes based on generalized finite difference discretization. The multistep methodology with power control is employed for simulating fully ionized propulsive flow of argon plasma through the thruster. Numerical solution shows convergence of every part of the solver including grid stability causing the multistep hybrid method to converge for a rated power delivery. Simulation results are reasonably in agreement with the reported physics of plasma flow in the thruster thus indicating the potential utility of this hybrid computational framework, especially when single fluid approximation of plasma is relevant.

Nutritional questions relevant to space flight

NASA Technical Reports Server (NTRS)

Lane, Helen W.; Schulz, Leslie O.

1992-01-01

This historical review of nutritionally related research in the U.S. and Soviet space programs discusses the uses of nutrition as a countermeasure to the effects of microgravity, with respect to body composition and to exercise. Available information is reviewed from space and ground research in the nutritional requirements for energy, protein, fluids, electrolytes, vitamins, and minerals. Past, present, and future systems for nutrient delivery in space are described, and finally, future directions and challenges are presented.

Nano- and microparticles at fluid and biological interfaces.

PubMed

Dasgupta, S; Auth, T; Gompper, G

2017-09-20

Systems with interfaces are abundant in both technological applications and biology. While a fluid interface separates two fluids, membranes separate the inside of vesicles from the outside, the interior of biological cells from the environment, and compartmentalize cells into organelles. The physical properties of interfaces are characterized by interface tension, those of membranes are characterized by bending and stretching elasticity. Amphiphilic molecules like surfactants that are added to a system with two immiscible fluids decrease the interface tension and induce a bending rigidity. Lipid bilayer membranes of vesicles can be stretched or compressed by osmotic pressure; in biological cells, also the presence of a cytoskeleton can induce membrane tension. If the thickness of the interface or the membrane is small compared with its lateral extension, both can be described using two-dimensional mathematical surfaces embedded in three-dimensional space. We review recent work on the interaction of particles with interfaces and membranes. This can be micrometer-sized particles at interfaces that stabilise emulsions or form colloidosomes, as well as typically nanometer-sized particles at membranes, such as viruses, parasites, and engineered drug delivery systems. In both cases, we first discuss the interaction of single particles with interfaces and membranes, e.g. particles in external fields, non-spherical particles, and particles at curved interfaces, followed by interface-mediated interaction between two particles, many-particle interactions, interface and membrane curvature-induced phenomena, and applications.

Nano- and microparticles at fluid and biological interfaces

NASA Astrophysics Data System (ADS)

Dasgupta, S.; Auth, T.; Gompper, G.

2017-09-01

Systems with interfaces are abundant in both technological applications and biology. While a fluid interface separates two fluids, membranes separate the inside of vesicles from the outside, the interior of biological cells from the environment, and compartmentalize cells into organelles. The physical properties of interfaces are characterized by interface tension, those of membranes are characterized by bending and stretching elasticity. Amphiphilic molecules like surfactants that are added to a system with two immiscible fluids decrease the interface tension and induce a bending rigidity. Lipid bilayer membranes of vesicles can be stretched or compressed by osmotic pressure; in biological cells, also the presence of a cytoskeleton can induce membrane tension. If the thickness of the interface or the membrane is small compared with its lateral extension, both can be described using two-dimensional mathematical surfaces embedded in three-dimensional space. We review recent work on the interaction of particles with interfaces and membranes. This can be micrometer-sized particles at interfaces that stabilise emulsions or form colloidosomes, as well as typically nanometer-sized particles at membranes, such as viruses, parasites, and engineered drug delivery systems. In both cases, we first discuss the interaction of single particles with interfaces and membranes, e.g. particles in external fields, non-spherical particles, and particles at curved interfaces, followed by interface-mediated interaction between two particles, many-particle interactions, interface and membrane curvature-induced phenomena, and applications.

Parenteral fluid regimens for improving functional outcome in people with acute stroke.

PubMed

Visvanathan, Akila; Dennis, Martin; Whiteley, William

2015-09-01

Parenteral fluids are commonly used in people with acute stroke with poor oral fluid intake. However, the balance between benefit and harm for different fluid regimens is unclear. To assess whether different parenteral fluid regimens lead to differences in death, or death or dependence, after stroke based on fluid type, fluid volume, duration of fluid administration, and mode of delivery. We searched the Cochrane Stroke Group Trials Register (May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE) (Cochrane Library 2015, Issue 5), MEDLINE (2008 to May 2015), EMBASE (2008 to May 2015), and CINAHL (1982 to May 2015). We also searched ongoing trials registers (May 2015) and reference lists, performed cited reference searches, and contacted authors. Randomised trials of parenteral fluid regimens in adults with ischaemic or haemorrhagic stroke within seven days of stroke onset that reported death or dependence. One review author screened titles and abstracts. We obtained the full-text articles of relevant studies, and two review authors independently selected trials for inclusion and extracted data. We used Cochrane's tool for bias assessment. We included 12 studies (2351 participants: range 27 to 841).Characteristics: The 12 included studies compared hypertonic (colloids) with isotonic fluids (crystalloids); of these, five studies (1420 participants) also compared 0.9% saline with another fluid. No data were available to make other comparisons. Delay from stroke to recruitment varied from less than 24 hours to 72 hours. Duration of fluid delivery was between two hours and 10 days.Bias assessment: Investigators and participants in eight of the 12 included studies were blind to treatment allocation, seven of the 12 included studies gave details of randomisation, and eight of the 12 included studies reported all outcomes measured. There were no relevant completed trials that addressed the effect of volume, duration, or mode of fluid delivery on death or dependence in people with stroke.The odds of death or dependence were similar in participants allocated to colloids or crystalloid fluid regimens (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.79 to 1.21, five studies, I² = 58%, low-quality evidence), and between 0.9% saline or other fluid regimens (OR 1.04, 95% CI 0.82 to 1.32, three studies, I² = 71%, low-quality evidence). There was substantial heterogeneity in these estimates.The odds of death were similar between colloids and crystalloids (OR 1.02, 95% CI 0.82 to 1.27, 12 studies, I² = 24%, moderate-quality evidence), and 0.9% saline and other fluids (OR 0.87, 95% CI 0.67 to 1.12, five studies, I² = 53%, low-quality evidence). The odds of pulmonary oedema were higher in participants allocated to colloids (OR 2.34, 95% CI 1.28 to 4.29, I² = 0%). Although the studies observed a higher risk of cerebral oedema (OR 0.20, 95% CI 0.02 to 1.74) and pneumonia (OR 0.58, 95% CI 0.17 to 2.01) with crystalloids, we could not exclude clinically important benefits or harms. We found no evidence that colloids were associated with lower odds of death or dependence in the medium term after stroke compared with crystalloids, though colloids were associated with greater odds of pulmonary oedema. We found no evidence to guide the best volume, duration, or mode of parenteral fluid delivery for people with acute stroke.

Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways.

PubMed

Donnelley, M; Siu, K K W; Jamison, R A; Parsons, D W

2012-01-01

Although airway gene transfer research in mouse models relies on bolus fluid dosing into the nose or trachea, the dynamics and immediate fate of delivered gene transfer agents are poorly understood. In particular, this is because there are no in vivo methods able to accurately visualize the movement of fluid in small airways of intact animals. Using synchrotron phase-contrast X-ray imaging, we show that the fate of surrogate fluid doses delivered into live mouse airways can now be accurately and non-invasively monitored with high spatial and temporal resolution. This new imaging approach can help explain the non-homogenous distributions of gene expression observed in nasal airway gene transfer studies, suggests that substantial dose losses may occur at deliver into mouse trachea via immediate retrograde fluid motion and shows the influence of the speed of bolus delivery on the relative targeting of conducting and deeper lung airways. These findings provide insight into some of the factors that can influence gene expression in vivo, and this method provides a new approach to documenting and analyzing dose delivery in small-animal models.

Field Test of Enhanced Remedial Amendment Delivery Using a Shear-Thinning Fluid

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

Truex, Michael J.; Vermeul, Vincent R.; Adamson, David

2015-03-01

Heterogeneity of hydraulic properties in aquifers may lead to contaminants residing in lower-permeability zones where it is difficult to deliver remediation amendments using conventional injection processes. The focus of this effort is to examine use of a shear-thinning fluid (STF) to improve the uniformity of remedial amendment distribution within a heterogeneous aquifer. Previous studies have demonstrated the significant potential of STFs for improving remedial amendment delivery in heterogeneous aquifers, but quantitative evaluation of these improvements from field applications are lacking. A field-scale test was conducted that compares data from successive injection of a tracer in water followed by injection ofmore » a tracer in a STF to evaluate the impact of the STF on tracer distribution uniformity in the presence of permeability contrasts within the targeted injection zone. Data from tracer breakthrough at multiple depth-discrete monitoring intervals and electrical resistivity tomography showed that inclusion of STF in the injection solution slowed movement in high-permeability pathways, improved delivery of amendment to low-permeability materials, and resulted in better uniformity in injected fluid distribution within the targeted treatment zone.« less

Neural network computer simulation of medical aerosols.

PubMed

Richardson, C J; Barlow, D J

1996-06-01

Preliminary investigations have been conducted to assess the potential for using artificial neural networks to simulate aerosol behaviour, with a view to employing this type of methodology in the evaluation and design of pulmonary drug-delivery systems. Details are presented of the general purpose software developed for these tasks; it implements a feed-forward back-propagation algorithm with weight decay and connection pruning, the user having complete run-time control of the network architecture and mode of training. A series of exploratory investigations is then reported in which different network structures and training strategies are assessed in terms of their ability to simulate known patterns of fluid flow in simple model systems. The first of these involves simulations of cellular automata-generated data for fluid flow through a partially obstructed two-dimensional pipe. The artificial neural networks are shown to be highly successful in simulating the behaviour of this simple linear system, but with important provisos relating to the information content of the training data and the criteria used to judge when the network is properly trained. A second set of investigations is then reported in which similar networks are used to simulate patterns of fluid flow through aerosol generation devices, using training data furnished through rigorous computational fluid dynamics modelling. These more complex three-dimensional systems are modelled with equal success. It is concluded that carefully tailored, well trained networks could provide valuable tools not just for predicting but also for analysing the spatial dynamics of pharmaceutical aerosols.

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.

Production and delivery of a fluid mixture to an annular volume of a wellbore

DOEpatents

Hermes, Robert E [Los Alamos, NM; Bland, Ronald Gene [Houston, TX; Foley, Ron Lee [Magnolia, TX; Bloys, James B [Katy, TX; Gonzalez, Manuel E [Kingwood, NM; Daniel, John M [Germantown, TN; Robinson, Ian M [Guisborough, GB; Carpenter, Robert B [Tomball, TX

2012-01-24

The methods described herein generally relate to preparing and delivering a fluid mixture to a confined volume, specifically an annular volume located between two concentrically oriented casing strings within a hydrocarbon fluid producing well. The fluid mixtures disclosed herein are useful in controlling pressure in localized volumes. The fluid mixtures comprise at least one polymerizable monomer and at least one inhibitor. The processes and methods disclosed herein allow the fluid mixture to be stored, shipped and/or injected into localized volumes, for example, an annular volume defined by concentric well casing strings.

In Silico Models of Aerosol Delivery to the Respiratory Tract – Development and Applications

PubMed Central

Longest, P. Worth; Holbrook, Landon T.

2011-01-01

This review discusses the application of computational models to simulate the transport and deposition of inhaled pharmaceutical aerosols from the site of particle or droplet formation to deposition within the respiratory tract. Traditional one-dimensional (1-D) whole-lung models are discussed briefly followed by a more in-depth review of three-dimensional (3-D) computational fluid dynamics (CFD) simulations. The review of CFD models is organized into sections covering transport and deposition within the inhaler device, the extrathoracic (oral and nasal) region, conducting airways, and alveolar space. For each section, a general review of significant contributions and advancements in the area of simulating pharmaceutical aerosols is provided followed by a more in-depth application or case study that highlights the challenges, utility, and benefits of in silico models. Specific applications presented include the optimization of an existing spray inhaler, development of charge-targeted delivery, specification of conditions for optimal nasal delivery, analysis of a new condensational delivery approach, and an evaluation of targeted delivery using magnetic aerosols. The review concludes with recommendations on the need for more refined model validations, use of a concurrent experimental and CFD approach for developing aerosol delivery systems, and development of a stochastic individual path (SIP) model of aerosol transport and deposition throughout the respiratory tract. PMID:21640772

In vivo performance of a microelectrode neural probe with integrated drug delivery

PubMed Central

Rohatgi, Pratik; Langhals, Nicholas B.; Kipke, Daryl R.; Patil, Parag G.

2014-01-01

Object The availability of sophisticated neural probes is a key prerequisite in the development of future brain machine interfaces (BMI). In this study, we developed and validated a neural probe design capable of simultaneous drug delivery and electrophysiology recordings in vivo. Focal drug delivery has promise to dramatically extend the recording lives of neural probes, a limiting factor to clinical adoption of BMI technology. Methods To form the multifunctional neural probe, we affixed a 16-channel microfabricated silicon electrode array to a fused silica catheter. Three experiments were conducted to characterize the performance of the device. Experiment 1 examines cellular damage from probe insertion and the drug distribution in tissue. Experiment 2 measures the effects of saline infusions delivered through the probe on concurrent electrophysiology. Experiment 3 demonstrates that a physiologically relevant amount of drug can be delivered in a controlled fashion. For these experiments, Hoechst and propidium iodide were used to assess insertion trauma and the tissue distribution of the infusate. Artificial cerebral spinal fluid and tetrodotoxin were injected to determine the efficacy of drug delivery. Results The newly developed multifunctional neural probes were successfully inserted into rat cortex and were able to deliver fluids and drugs that resulted in the expected electrophysiological and histological responses. The damage from insertion of the device into brain tissue was substantially less than the volume of drug dispersion in tissue. Electrophysiological activity, including both individual spikes as well as local field potentials, was successfully recorded with this device during real-time drug delivery. No significant changes were seen in response to delivery of artificial cerebral spinal fluid as a control experiment, whereas delivery of tetrodotoxin produced the expected result of suppressing all spiking activity in the vicinity of the catheter outlet. Conclusions Multifunctional neural probes such as the ones developed and validated within this study have great potential to help further understand the design space and criteria for the next generation of neural probe technology. By incorporating integrated drug delivery functionality into the probes, new treatment options for neurological disorders and regenerative neural interfaces utilizing localized and feedback controlled delivery of drugs can be realized in the near future. PMID:19569896

Development of a probiotic delivery system from agrowastes, soy protein isolate, and microbial transglutaminase.

PubMed

Yew, Sok-Eng; Lim, Ting-Jin; Lew, Lee-Ching; Bhat, Rajeev; Mat-Easa, Azhar; Liong, Min-Tze

2011-04-01

Probiotic delivery system was developed via the use of microbial transglutaminase (MTG) cross-linked soy protein isolate (SPI) incorporated with agrowastes such as banana peel (BE), banana pulp (BU), and pomelo rind (PR). Inoculums of Lactobacillus bulgaricus FTDC 1511 were added to the cross-linked protein matrix. The incorporation of agrowastes had significantly (P<0.05) reduced the strength, pH value, and the lightness of the SPI gel carriers, while sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles revealed that the occurring cross-links within the SPI gel carriers were attributed to the addition of MTG. Scanning electron microscope micrographs illustrated that SPI carriers containing agrowastes have exhibited a less-dense protein matrix. All the SPI carriers possessed maximum swelling ratio at 4 to 4.5 within 15 min in simulated gastric fluid (SGF), whereas the maximum swelling ratios of SPI/BE, SPI/BU, and SPI/PR were higher compared to that of control in simulated intestinal fluid (SIF). Additionally, SPI carriers in SGF medium did not show degradation of structure, whereas a major collapse of network was observed in SIF medium, indicating controlled-release in the intestines. The addition of agrowastes into SPI carriers led to a significantly (P<0.0001) lower release of L. bulgaricus FTDC 1511 in SGF medium and a higher release in SIF medium, compared to that of the control. SPI carriers containing agrowastes may be useful transports for living probiotic cells through the stomach prior to delivery in the lower intestines.   Agrowastes could be utilized as a new probiotic carrier for enhanced gastrointestinal transit and during storage. This also reduces the amount of agrowastes accumulated.

Effect of 1.2% of simvastatin gel as a local drug delivery system on Gingival Crevicular Fluid interleukin-6 & interleukin-8 levels in non surgical treatment of chronic periodontitis patients.

PubMed

Gunjiganur Vemanaradhya, Gayathri; Emani, Shilpa; Mehta, Dhoom Singh; Bhandari, Shilpy

2017-10-01

The present study was carried out to evaluate the effect of 1.2% simvastatin gel as local drug delivery (LDD) system on Gingival Crevicular Fluid (GCF) Interleukin -6 (IL-6) and Interleukin-8 (IL-8) levels in chronic periodontitis patients, in addition to scaling and root planing (SRP). A total of 46 chronic periodontitis patients were equally divided into two groups. Group I patients were treated by SRP; Group II patients were treated by SRP followed by LDD of 1.2% simvastatin (SMV) gel. Plaque index (PI), Gingival index(GI), Sulcus Bleeding Index (SBI), Probing pocket depth (PPD) and Relative clinical attachment level (CAL) were recorded & GCF samples were collected at baseline (0day) and at 45th day from both the groups. The collected GCF samples were analysed for IL-6 and IL-8 levels with enzyme-linked immunosorbent assay (ELISA). Both the groups showed significant reduction in all the clinical parameters scores and IL-6 and IL-8 levels after non-surgical periodontal therapy (SRP for group I/SRP+1.2% SMV gel for group II) in contrast to baseline values. However, a greater reduction was observed in group II. A non-significant positive correlation was observed between clinical parameters and IL-6 and IL-8 levels except at baseline, a significant correlation was observed between PPD &IL 6 levels in group II. In adjunct to SRP, 1.2% Simvastatin gel acts as an effective local drug delivery agent for the management of chronic periodontitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation and Evaluation of Newly Developed Chitosan Salt Coating Dispersions for Colon Delivery without Requiring Overcoating.

PubMed

Yamada, Kyohei; Iwao, Yasunori; Bani-Jaber, Ahmad; Noguchi, Shuji; Itai, Shigeru

2015-01-01

Although chitosan (CS) has been recognized as a good material for colon-specific drug delivery systems, an overcoating with an enteric coating polymer on the surface of CS is absolutely necessary because CS is soluble in acidic conditions before reaching the colon. In the present study, to improve its stability in the presence of acid, a newly developed CS-laurate (CS-LA) material was evaluated as a coating dispersion for the development of colon-specific drug delivery systems. Two types of CS with different molecular weights, CS250 and CS600, were used to prepare CS-LA films by the casting method. The CS250-LA films had smooth surfaces, whereas the surfaces of the CS600-LA films were rough, indicating that the CS250-LA dispersion could form a denser film than CS600-LA. Both of these CS-LA films maintained a constant shape over 22 h in a pH 1.2 HCl/NaCl buffer, where the corresponding CS films rapidly disintegrated. In addition, the CS250-LA film showed specific colon degradability in a pH 6.0 phosphate buffered solution containing 1.0% (w/v) β-glucosidase. As a result of tensile strength and elongation at the break, both CS-LA films were found to have flexible film properties. Finally, the release of acetaminophen from disks coated with CS250-LA dispersions was significantly suppressed in fluids at pH 1.2 and 6.8, whereas disks coated with CS solution rapidly released the drug in pH 1.2 fluids. Taken together, this study shows that LA modification could be a useful approach in preparing CS films with acid stability and colonic degradability properties without requiring overcoating.

Effect of diode-laser and AC magnetic field of bovine serum albumin nanospheres loaded with phthalocyanine and magnetic particles.

PubMed

Simioni, Andreza Ribeiro; Rodrigues, Marcilene M A; Primo, Fernando L; Morais, Paulo C; Tedesco, Antonio Claudio

2011-04-01

This study reports on the development and characterization of bovine serum albumin (BSA) nanospheres containing Silicon(IV) phthalocyanine (NzPc) and/or maghemite nanoparticles (MNP), the latter introduced via ionic magnetic fluid (MF). The nanosized BSA-loaded samples were designed for synergic application while combining Photodynamic Therapy and Hyperthermia. Incorporation of MNP in the albumin-based template, allowing full control of the magnetic content, was accomplished by adding a highly-stable ionic magnetic fluid sample to the albumin suspension, following heat denaturing. The material's evaluation was performed using Zeta potential measurements and scanning electron microscopy. The samples were characterized by steady-state techniques and time-resolved fluorescence. The in vitro assay, using human fibroblasts, revealed no cytotoxic effect in all samples investigated, demonstrating the potential of the tested system as a synergistic drug delivery system.

Biochemical sensor tubing for point-of-care monitoring of intravenous drugs and metabolites.

PubMed

Choi, Charles J; Wu, Hsin-Yu; George, Sherine; Weyhenmeyer, Jonathan; Cunningham, Brian T

2012-02-07

In medical facilities, there is strong motivation to develop detection systems that can provide continuous analysis of fluids in medical tubing used to either deliver or remove fluids from a patient's body. Possible applications include systems that increase the safety of intravenous (IV) drug injection and point-of-care health monitoring. In this work, we incorporated a surface-enhanced Raman scattering (SERS) sensor comprised of an array of closely spaced metal nanodomes into flexible tubing commonly used for IV drug delivery and urinary catheters. The nanodome sensor was fabricated by a low-cost, large-area process that enables single use disposable operation. As exemplary demonstrations, the sensor was used to kinetically detect promethazine (pain medication) and urea (urinary metabolite) within their clinically relevant concentration ranges. Distinct SERS peaks for each analyte were used to demonstrate separate detection and co-detection of the analytes.

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

PubMed

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

2017-01-01

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

Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

PubMed

Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

2016-06-01

Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment. © 2016 John Wiley & Sons A/S.

Starch-based nanocapsules fabricated through layer-by-layer assembly for oral delivery of protein to lower gastrointestinal tract.

PubMed

Zhang, Yiping; Chi, Chengdeng; Huang, Xiaoyi; Zou, Qin; Li, Xiaoxi; Chen, Ling

2017-09-01

Anionic carboxymethyl starch (CMS) and cationic quaternary ammonium starch (QAS), were used to fabricate nanocapsules through electrostatic layer by layer (LbL) alternate deposition onto colloidal BSA particles. An ideal starch-based colloidal nanocapsule was achieved by adjusting the degree of substitution (DS) and weight average molecular molar mass (M w ) of CMS. The nanocapsules fabricated by CMS with lower DS or M w possessed more compact and stable core-shell structure, which favoured the BSA delivery from the upper gastrointestinal tract (GIT) to the colon. In particular, CMS/QAS nanocapsules constructed by CMS with lower DS and M w showed better colon-specific delivery and release performance in simulated GIT fluid after 7days' storage in different kinds of beverage (33.04%-46.35% in upper GIT, 52.70%-64.97% in colon, respectively). These findings demonstrated that CMS/QAS nanocapsules constructed by CMS with lower DS and M w can be further exploited as a potential oral delivery system for protein to colon. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prophylactic transabdominal amnioinfusion in oligohydramnios for preterm premature rupture of membranes: increase of amniotic fluid index during latency period.

PubMed

Garzetti, G G; Ciavattini, A; De Cristofaro, F; La Marca, N; Arduini, D

1997-01-01

This study was designed to: (i) evaluate the effect of amnioinfusion on the latency period in patients with oligohydramnios for preterm premature rupture of membranes, and (ii) to investigate the relationship between changes in the amniotic fluid index and fetal heart rate short-term variability by computerized Hewlett-Packard cardiotocography, longitudinally estimated before and after prophylactic amnioinfusion. All singleton pregnancies with prolonged premature rupture of membranes after 25 weeks of gestation and seen at the Institute of Obstetrics and Gynecology, University of Ancona (Italy), between January 1994 and June 1995 were included in the study. Transabdominal amnioinfusion with 150-350 ml warmed normal saline (25-50 ml/min) was performed at weekly intervals. Amniotic fluid volume was assessed ultrasonographically by means of the four-quadrant technique on a weekly basis before and after each amnioinfusion, as well as the short-term variability by a Hewlett-Packard computerized cardiotocographic system. 18 women were enrolled and underwent prophylactic transabdominal amnioinfusion at weekly intervals until delivery. Eighteen controls, who did not undergo prophylactic amnioinfusion, were recruited from our 1992-1993 series and included in the study. The median interval between premature rupture of membranes and delivery was 3.0 weeks (range 1-8 weeks), with an average delivery age of 33.0 weeks (range 27-36 weeks). The latency period was significantly longer in patients who underwent prophylactic amnioinfusion (mean +/- SD, 4.1 +/- 1.7 weeks) than in controls(1.7 +/- 1.0 weeks; p < 0.001). An increase in both the weekly amniotic fluid index (linear regression analysis r = 0.8, p = 0.03) and the weekly short-term variability (linear regression analysis r = 0.82, p = 0.02) was observed among patients who underwent prophylactic amnioinfusion. A direct relationship was observed between the amniotic fluid index and short-term variability (linear regression analysis r = 0.54, p = 0.04). The mean values of fetal movements recorded by computerized tomography during the 20 min of observation significantly increased after amnioinfusion in comparison with those before it (2.6 +/- 0.9 and 0.9 +/- 0.7 respectively; p = 0.001). The present study has shown a positive effect of prophylactic transabdominal amnioinfusion on the latency period in patients with preterm premature rupture of membranes and oligohydramnios. Among the patients who underwent amnioinfusion, an interesting improvement in fetal heart rate short-term variability was associated with the progressive increase in amniotic fluid volume, as an expression of fetal well-being.

COMPUTATIONAL FLUID DYNAMICS MODELING OF SCALED HANFORD DOUBLE SHELL TANK MIXING - CFD MODELING SENSITIVITY STUDY RESULTS

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

JACKSON VL

2011-08-31

The primary purpose of the tank mixing and sampling demonstration program is to mitigate the technical risks associated with the ability of the Hanford tank farm delivery and celtification systems to measure and deliver a uniformly mixed high-level waste (HLW) feed to the Waste Treatment and Immobilization Plant (WTP) Uniform feed to the WTP is a requirement of 24590-WTP-ICD-MG-01-019, ICD-19 - Interface Control Document for Waste Feed, although the exact definition of uniform is evolving in this context. Computational Fluid Dynamics (CFD) modeling has been used to assist in evaluating scaleup issues, study operational parameters, and predict mixing performance atmore » full-scale.« less

A fluid collection system for dermal wounds in clinical investigations

PubMed Central

Klopfer, Michael; Li, G.-P.; Widgerow, Alan; Bachman, Mark

2016-01-01

In this work, we demonstrate the use of a thin, self adherent, and clinically durable patch device that can collect fluid from a wound site for analysis. This device is manufactured from laminated silicone layers using a novel all-silicone double-molding process. In vitro studies for flow and delivery were followed by a clinical demonstration for exudate collection efficiency from a clinically presented partial thickness burn. The demonstrated utility of this device lends itself for use as a research implement used to clinically sample wound exudate for analysis. This device can serve as a platform for future integration of wearable technology into wound monitoring and care. The demonstrated fabrication method can be used for devices requiring thin membrane construction. PMID:27051470

Elastic contact mechanics: percolation of the contact area and fluid squeeze-out.

PubMed

Persson, B N J; Prodanov, N; Krick, B A; Rodriguez, N; Mulakaluri, N; Sawyer, W G; Mangiagalli, P

2012-01-01

The dynamics of fluid flow at the interface between elastic solids with rough surfaces depends sensitively on the area of real contact, in particular close to the percolation threshold, where an irregular network of narrow flow channels prevails. In this paper, numerical simulation and experimental results for the contact between elastic solids with isotropic and anisotropic surface roughness are compared with the predictions of a theory based on the Persson contact mechanics theory and the Bruggeman effective medium theory. The theory predictions are in good agreement with the experimental and numerical simulation results and the (small) deviation can be understood as a finite-size effect. The fluid squeeze-out at the interface between elastic solids with randomly rough surfaces is studied. We present results for such high contact pressures that the area of real contact percolates, giving rise to sealed-off domains with pressurized fluid at the interface. The theoretical predictions are compared to experimental data for a simple model system (a rubber block squeezed against a flat glass plate), and for prefilled syringes, where the rubber plunger stopper is lubricated by a high-viscosity silicon oil to ensure functionality of the delivery device. For the latter system we compare the breakloose (or static) friction, as a function of the time of stationary contact, to the theory prediction.

Magnetic targeting to enhance microbubble delivery in an occluded microarterial bifurcation

NASA Astrophysics Data System (ADS)

de Saint Victor, M.; Carugo, D.; Barnsley, L. C.; Owen, J.; Coussios, C.-C.; Stride, E.

2017-09-01

Ultrasound and microbubbles have been shown to accelerate the breakdown of blood clots both in vitro and in vivo. Clinical translation of this technology is still limited, however, in part by inefficient microbubble delivery to the thrombus. This study examines the obstacles to delivery posed by fluid dynamic conditions in occluded vasculature and investigates whether magnetic targeting can improve microbubble delivery. A 2D computational fluid dynamic model of a fully occluded Y-shaped microarterial bifurcation was developed to determine: (i) the fluid dynamic field in the vessel with inlet velocities from 1-100 mm s-1 (corresponding to Reynolds numbers 0.25-25) (ii) the transport dynamics of fibrinolytic drugs; and (iii) the flow behavior of microbubbles with diameters in the clinically-relevant range (0.6-5 µm). In vitro experiments were carried out in a custom-built microfluidic device. The flow field was characterized using tracer particles, and fibrinolytic drug transport was assessed using fluorescence microscopy. Lipid-shelled magnetic microbubbles were fluorescently labelled to determine their spatial distribution within the microvascular model. In both the simulations and experiments, the formation of laminar vortices and an abrupt reduction of fluid velocity were observed in the occluded branch of the bifurcation, severely limiting drug transport towards the occlusion. In the absence of a magnetic field, no microbubbles reached the occlusion, remaining trapped in the first vortex, within 350 µm from the bifurcation center. The number of microbubbles trapped within the vortex decreased as the inlet velocity increased, but was independent of microbubble size. Application of a magnetic field (magnetic flux density of 76 mT, magnetic flux density gradient of 10.90 T m-1 at the centre of the bifurcation) enabled delivery of microbubbles to the occlusion and the number of microbubbles delivered increased with bubble size and with decreasing inlet velocity.

Large effect of membrane tension on the fluid-solid phase transitions of two-component phosphatidylcholine vesicles.

PubMed

Chen, Dong; Santore, Maria M

2014-01-07

Model phospholipid membranes and vesicles have long provided insight into the nature of confined materials and membranes while also providing a platform for drug delivery. The rich thermodynamic behavior and interesting domain shapes in these membranes have previously been mapped in extensive studies that vary temperature and composition; however, the thermodynamic impact of tension on bilayers has been restricted to recent reports of subtly reduced fluid-fluid transition temperatures. In two-component phosphatidylcholine unilamellar vesicles [1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)], we report a dramatic influence of tension on the fluid-solid transition and resulting phases: At fixed composition, systematic variations in tension produce differently shaped solid domains (striped or irregular hexagons), shift fluid-solid transition temperatures, and produce a triple-point-like intersection of coexistence curves at elevated tensions, about 3 mN/m for 30% DOPC/70% DPPC. Tension therefore represents a potential switch of microstructure in responsive engineered materials; it is an important morphology-determining variable in confined systems, and, in biological membranes, it may provide a means to regulate dynamic structure.

Fluid Delivery System For Capillary Electrophoretic Applications.

DOEpatents

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

2002-04-23

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

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain.

PubMed

Grinevich, Valery; Knobloch-Bollmann, H Sophie; Eliava, Marina; Busnelli, Marta; Chini, Bice

2016-02-01

Oxytocin (OT) is a neuropeptide, which can be seen to be one of the molecules of the decade due to its profound prosocial effects in nonvertebrate and vertebrate species, including humans. Although OT can be detected in various physiological fluids (blood, saliva, urine, cerebrospinal fluid) and brain tissue, it is unclear whether peripheral and central OT releases match and synergize. Moreover, the pathways of OT delivery to brain regions involved in specific behaviors are far from clear. Here, we discuss the evolutionarily and ontogenetically determined pathways of OT delivery and OT signaling, which orchestrate activity of the mesolimbic social decision-making network. Furthermore, we speculate that both the alteration in OT delivery and OT receptor expression may cause behavioral abnormalities in patients afflicted with psychosocial diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Recent Progress of Microfluidics in Translational Applications

PubMed Central

Liu, Zongbin; Han, Xin

2016-01-01

Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed. PMID:27091777

Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

PubMed Central

Li, Chong; Zhang, Yan; Su, Tingting; Feng, Lianlian; Long, Yingying; Chen, Zhangbao

2012-01-01

We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs) having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs) without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability. PMID:23233804

Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin.

PubMed

Li, Chong; Zhang, Yan; Su, Tingting; Feng, Lianlian; Long, Yingying; Chen, Zhangbao

2012-01-01

We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs) having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs) without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability.

Structure, corrosion behavior and mechanical property of a novel poly(vinyl alcohol) composite in simulated body fluid.

PubMed

Li, Juan; Suo, Jinping; Zou, Peng; Jia, Lintao; Wang, Shifang

2010-01-01

The data for long-term drug-delivery systems are scarce compared to the short-term systems because the required research efforts are more time-consuming. In this study, we report a novel cross-linked composite based on poly(vinyl alcohol) (PVA) containing cupric ions for long-term delivery, which is helpful for contraception and trace element balance in the human body. The composition, corrosion products, crystal structure, chemical structure and mechanical stability of the composite, after being immersed in simulated body fluid (SBF) for one year, were studied by X-ray fluorescence spectroscopy (XRF), X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and mechanical testing. The results show that no other new elements, such as P, Cl and Ca, appear on the surface of the composite and no Cu(2)O was formed after immersion in SBF for one year. The effectiveness of copper can be greatly improved and the side-effects caused by these compounds might also be eliminated. Furthermore, this novel composite exhibits long-term mechanical stability in SBF. The present in vitro long-term data suggest that this novel copper-containing composite may serve as a substitute for conventional materials of copper-containing intrauterine devices (Cu-IUDs) and as a carrier for controlled-release material in a variety of other applications.

Enhanced Amendment Delivery to Low Permeability Zones for Chlorinated Solvent Source Area Bioremediation

DTIC Science & Technology

2014-10-01

enhanced amendments delivery process, a non-toxic biodegradable polymer, such as xanthan gum, is added to the injection solution to form a non- Newtonian...Once injection stops, the injected fluid viscosity increases and creates a more stable zone for biodegradation reactions because the amendment-laden...electron acceptors and biodegradation of the shear-thinning agent. • Determine the cost factors for applying the STF enhanced delivery technology

Hybrid microneedles devices for diagnostic and therapeutic applications: fabrication and preliminary results

NASA Astrophysics Data System (ADS)

Dardano, P.; Caliò, A.; Politi, J.; Di Palma, V.; Bevilacqua, M. F.; Rea, I.; Casalino, M.; Di Matteo, A.; Rendina, I.; De Stefano, L.

2015-06-01

Microneedles are newly developed biomedical devices, whose advantages are mainly in the non-invasiveness, discretion and versatility of use both as diagnostics and as therapeutics tool. In fact, they can be used both for drugs delivery in the interstitial fluids and for the analysis of the interstitial fluid. In this work we present the preliminary results for two devices based on micro needles in PolyEthylene (Glycol). The first for the drugs delivery includes a membrane whose optical reflected wavelength is related to the concentration of drug. Here, we present our preliminary result in diffusion of drugs between the membrane and the microneedles. The second device is gold coated and it works as electrode for the electrochemical detection of species in the interstitial fluid. A preliminary result in detection of glucose will be shown.

Coupling LAMMPS with Lattice Boltzmann fluid solver: theory, implementation, and applications

NASA Astrophysics Data System (ADS)

Tan, Jifu; Sinno, Talid; Diamond, Scott

2016-11-01

Studying of fluid flow coupled with solid has many applications in biological and engineering problems, e.g., blood cell transport, particulate flow, drug delivery. We present a partitioned approach to solve the coupled Multiphysics problem. The fluid motion is solved by the Lattice Boltzmann method, while the solid displacement and deformation is simulated by Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS). The coupling is achieved through the immersed boundary method so that the expensive remeshing step is eliminated. The code can model both rigid and deformable solids. The code also shows very good scaling results. It was validated with classic problems such as migration of rigid particles, ellipsoid particle's orbit in shear flow. Examples of the applications in blood flow, drug delivery, platelet adhesion and rupture are also given in the paper. NIH.

A model for optimizing delivery of targeted radionuclide therapies into resection cavity margins for the treatment of primary brain cancers.

PubMed

Raghavan, Raghu; Howell, Roger W; Zalutsky, Michael R

2017-06-01

Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67 Ga, 77 Br, 111 In, 125 I, 123 I, 193m Pt, 195m Pt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.

Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting.

PubMed

Fukui, E; Miyamura, N; Uemura, K; Kobayashi, M

2000-08-25

As a new oral drug delivery system for colon targeting, enteric coated timed-release press-coated tablets (ETP tablets) were developed by coating enteric polymer on timed-release press-coated tablets composed of an outer shell of hydroxypropylcellulose and core tablet containing diltiazem hydrochloride (DIL) as a model drug. The results of the in vitro dissolution tests in JP 1st fluid (pH 1.2) and JP 2nd fluid (pH 6.8) indicated that these tablets showed both acid resistance and timed-release. To clarify whether ETP tablets could have been of use in the gastrointestinal tract, ETP tablets with a layer of phenylpropanolamine hydrochloride (PPA) (a marker of gastric emptying) between the enteric coating layer and outer shell were prepared, and were administered to beagle dogs. The gastric emptying time and lag time after gastric emptying were evaluated by determining the times at which PPA and DIL first appeared in the plasma (TFA(PPA) and TFA(DIL), respectively). TFA(PPA) and TFA(DIL) were about 4 and 7 h, respectively. This value of TFA(PPA) indicated that ETP tablets displayed acid resistance in the stomach as well as in JP Ist fluid. Subtraction of TFA(PPA) from TFA(DIL) gave a value of about 3 h which agreed well with the lag time determined by in vitro dissolution test in JP 2nd fluid. Also, the results seemed to be in accordance with the time at which the tablets reached the colon after gastric emptying. Therefore, ETP tablets seemed to be an effective tool for oral site-specific delivery including targeting of the colon.

Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

PubMed

Welter, Michael; Rieger, Heiko

2013-01-01

Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells.

The sheep as a model of preclinical safety and pharmacokinetic evaluations of candidate microbicides.

PubMed

Holt, Jonathon D S; Cameron, David; Dias, Nicola; Holding, Jeremy; Muntendam, Alex; Oostebring, Freddy; Dreier, Peter; Rohan, Lisa; Nuttall, Jeremy

2015-07-01

When developing novel microbicide products for the prevention of HIV infection, the preclinical safety program must evaluate not only the active pharmaceutical ingredient but also the product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an assessment of the pharmacokinetics, safety, tolerability, and local toxicity of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal Ring-004). We performed a 3-month general toxicology study, a preliminary pharmacokinetic study using drug-loaded vaginal gel, and a detailed assessment of the kinetics of dapivirine delivery to plasma, vaginal, and rectal fluid and rectal, vaginal, and cervical tissue over 28 days of exposure and 3 and 7 days after removal of the ring. The findings of the general toxicology study supported the existing data from both preclinical and clinical studies in that there were no signs of toxicity related to dapivirine. In addition, the presence of the physical dapivirine ring did not alter local or systemic toxicity or the pharmacokinetics of dapivirine. Pharmacokinetic studies indicated that the dapivirine ring produced significant vaginal tissue levels of dapivirine. However, no dapivirine was detected in cervical tissue samples using the methods described here. Plasma and vaginal fluid levels were lower than those in previous clinical studies, while there were detectable dapivirine levels in the rectal tissue and fluid. All tissue and fluid levels tailed off rapidly to undetectable levels following removal of the ring. The sheep represents a very useful model for the assessment of the safety and pharmacokinetics of microbicide drug delivery devices, such as the vaginal ring. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Out-of-Hospital Fluid in Severe Sepsis: Effect on Early Resuscitation in the Emergency Department

PubMed Central

Seymour, Christopher W.; Cooke, Colin R.; Mikkelsen, Mark E.; Hylton, Julie; Rea, Tom D.; Goss, Christopher H.; Gaieski, David F.; Band, Roger A.

2014-01-01

Background Early identification and treatment of patients with severe sepsis improves outcome, yet the role of out-of-hospital intravenous (IV) fluid is unknown. Objective To determine if the delivery of out-of-hospital fluid in patients with severe sepsis is associated with reduced time to achievement of goal-oriented resuscitation in the emergency department (ED). Methods We performed a secondary data analysis of a retrospective cohort study in a metropolitan, tertiary care, university-based medical center supported by a two-tiered system of out-of-hospital emergency medical services (EMS) providers. We studied the association between delivery of out-of-hospital fluid by advanced life support (ALS) providers and the achievement of resuscitation endpoints (central venous pressure [CVP] ≥8 mmHg, mean arterial pressure [MAP] ≥65 mmHg, and central venous oxygen saturation [ScvO2] ≥70%) within six hours after triage during early goal-directed therapy (EGDT) in the ED. Results Twenty five (48%) of 52 patients transported by ALS with severe sepsis received out-of-hospital fluid. Data for age, gender, source of sepsis, and presence of comorbidities were similar between patients who did and did not receive out-of-hospital fluid. Patients receiving out-of-hospital fluid had lower out-of-hospital mean (± standard deviation) systolic blood pressure (95 ± 40 mmHg vs. 117 ± 29 mmHg; p = 0.03) and higher median (interquartile range) Sequential Organ Failure Assessment (SOFA) scores in the ED (7 [5–8] vs. 4 [4–6]; p = 0.01) than patients not receiving out-of-hospital fluid. Despite greater severity of illness, patients receiving out-of-hospital fluid approached but did not attain a statistically significant increase in the likelihood of achieving MAP ≥65 mmHg within six hours after ED triage (70% vs. 44%, p = 0.09). On average, patients receiving out-of-hospital fluid received twice the fluid volume within one hour after ED triage (1.1 L [1.0–2.0 L] vs. 0.6 L [0.3–1.0 L]; p 0.01). No difference in achievement of goal CVP (72% vs. 60%; p = 0.6) or goal ScvO2 (54% vs. 36%; p = 0.25) was observed between groups. Conclusions Less than half of patients with severe sepsis transported by ALS received out-of-hospital fluid. Patients receiving out-of-hospital IV access and fluids approached but did not attain a statistically significant increase in the likelihood of achieving goal MAP during EGDT. These preliminary findings require additional investigation to evaluate the optimal role of out-of-hospital resuscitation in treating patients with severe sepsis. PMID:20199228

The Inclusion of Chitosan in Poly-ε-caprolactone Nanoparticles: Impact on the Delivery System Characteristics and on the Adsorbed Ovalbumin Secondary Structure.

PubMed

Jesus, Sandra; Fragal, Elizangela H; Rubira, Adley F; Muniz, Edvani C; Valente, Artur J M; Borges, Olga

2018-01-01

This report extensively explores the benefits of including chitosan into poly-ε-caprolactone (PCL) nanoparticles (NPs) to obtain an improved protein/antigen delivery system. Blend NPs (PCL/chitosan NPs) showed improved protein adsorption efficacy (84%) in low shear stress and aqueous environment, suggesting that a synergistic effect between PCL hydrophobic nature and the positive charges of chitosan present at the particle surface was responsible for protein interaction. Additionally, thermal analysis suggested the blend NPs were more stable than the isolated polymers and cytotoxicity assays in a primary cell culture revealed chitosan inclusion in PCL NPs reduced the toxicity of the delivery system. A quantitative 6-month stability study showed that the inclusion of chitosan in PCL NPs did not induce a change in adsorbed ovalbumin (OVA) secondary structure characterized by the increase in the unordered conformation (random coil), as it was observed for OVA adsorbed to chitosan NPs. Additionally, the slight conformational changes occurred, are not expected to compromise ovalbumin secondary structure and activity, during a 6-month storage even at high temperatures (45°C). In simulated biological fluids, PCL/chitosan NPs showed an advantageous release profile for oral delivery. Overall, the combination of PCL and chitosan characteristics provide PCL/chitosan NPs valuable features particularly important to the development of vaccines for developing countries, where it is difficult to ensure cold chain transportation and non-parenteral formulations would be preferred.

Open Source Tools for Temporally Controlled Rodent Behavior Suitable for Electrophysiology and Optogenetic Manipulations.

PubMed

Solari, Nicola; Sviatkó, Katalin; Laszlovszky, Tamás; Hegedüs, Panna; Hangya, Balázs

2018-01-01

Understanding how the brain controls behavior requires observing and manipulating neural activity in awake behaving animals. Neuronal firing is timed at millisecond precision. Therefore, to decipher temporal coding, it is necessary to monitor and control animal behavior at the same level of temporal accuracy. However, it is technically challenging to deliver sensory stimuli and reinforcers as well as to read the behavioral responses they elicit with millisecond precision. Presently available commercial systems often excel in specific aspects of behavior control, but they do not provide a customizable environment allowing flexible experimental design while maintaining high standards for temporal control necessary for interpreting neuronal activity. Moreover, delay measurements of stimulus and reinforcement delivery are largely unavailable. We combined microcontroller-based behavior control with a sound delivery system for playing complex acoustic stimuli, fast solenoid valves for precisely timed reinforcement delivery and a custom-built sound attenuated chamber using high-end industrial insulation materials. Together this setup provides a physical environment to train head-fixed animals, enables calibrated sound stimuli and precisely timed fluid and air puff presentation as reinforcers. We provide latency measurements for stimulus and reinforcement delivery and an algorithm to perform such measurements on other behavior control systems. Combined with electrophysiology and optogenetic manipulations, the millisecond timing accuracy will help interpret temporally precise neural signals and behavioral changes. Additionally, since software and hardware provided here can be readily customized to achieve a large variety of paradigms, these solutions enable an unusually flexible design of rodent behavioral experiments.

Pump for delivering heated fluids

NASA Technical Reports Server (NTRS)

Sabelman, E. E. (Inventor)

1973-01-01

A thermomechanical pump particularly suited for use in pumping a warming fluid obtained from an RTG (Radioisotope Thermal Generator) through science and flight instrumentation aboard operative spacecraft is described. The invention is characterized by a pair of operatively related cylinders, each including a reciprocating piston head dividing the cylinder into a pressure chamber confining therein a vaporizable fluid, and a pumping chamber for propelling the warming fluid, and a fluid delivery circuit for alternately delivering the warming fluid from the RTG through the pressure chamber of one cylinder to the pumping chamber of the other cylinder, whereby the vaporizable fluid within the pair of pressure chambers alternately is vaporized and condensed for driving the associated pistons in pumping and intake strokes.

Magnocellular Neurons and Posterior Pituitary Function.

PubMed

Brown, Colin H

2016-09-15

The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model

PubMed Central

Koskimäki, Janne; Tarkia, Miikka; Ahtola-Sätilä, Tuula; Saloranta, Lasse; Laakso, Aki; Frantzén, Janek

2015-01-01

Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant. PMID:25685803

Mathematical modeling of a process the rolling delivery

NASA Astrophysics Data System (ADS)

Stepanov, Mikhail A.; Korolev, Andrey A.

2018-03-01

An adduced analysis of the scientific researches in a domain of the rolling equipments, also research of properties the working material. A one of perspective direction of scientific research this is mathematical modeling. That is broadly used in many scientific disciplines and especially at the technical, applied sciences. With the aid of mathematical modeling it can be study of physical properties of the researching objects and systems. A research of the rolling delivery and transporting devices realized with the aid of a construction of mathematical model of appropriate process. To be described the basic principles and conditions of a construction of mathematical models of the real objects. For example to be consider a construction of mathematical model the rolling delivery device. For a construction that is model used system of the equations, which consist of: Lagrange’s equation of a motion, describing of the law conservation of energy of a mechanical system, and the Navier - Stokes equations, which characterize of the flow of a continuous non-compressed fluid. A construction of mathematical model the rolling deliver to let determined of a total energy of device, and therefore to got the dependence upon the power of drive to a gap between of rolls. A corroborate the hypothesis about laminar the flow of a material into the rolling gap of deliver.

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.

Transcending epithelial and intracellular biological barriers; a prototype DNA delivery device.

PubMed

McCaffrey, Joanne; McCrudden, Cian M; Ali, Ahlam A; Massey, Ashley S; McBride, John W; McCrudden, Maelíosa T C; Vicente-Perez, Eva M; Coulter, Jonathan A; Robson, Tracy; Donnelly, Ryan F; McCarthy, Helen O

2016-03-28

Microneedle technology provides the opportunity for the delivery of DNA therapeutics by a non-invasive, patient acceptable route. To deliver DNA successfully requires consideration of both extra and intracellular biological barriers. In this study we present a novel two tier platform; i) a peptide delivery system, termed RALA, that is able to wrap the DNA into nanoparticles, protect the DNA from degradation, enter cells, disrupt endosomes and deliver the DNA to the nucleus of cells ii) a microneedle (MN) patch that will house the nanoparticles within the polymer matrix, breach the skin's stratum corneum barrier and dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin. Our data demonstrates that the RALA is essential for preventing DNA degradation within the poly(vinylpyrrolidone) (PVP) polymer matrix. In fact the RALA/DNA nanoparticles (NPs) retained functionality when in the MN arrays after 28days and over a range of temperatures. Furthermore the physical strength and structure of the MNs was not compromised when loaded with the NPs. Finally we demonstrated the effectiveness of our MN-NP platform in vitro and in vivo, with systemic gene expression in highly vascularised regions. Taken together this 'smart-system' technology could be applied to a wide range of genetic therapies. Copyright © 2016. Published by Elsevier B.V.

Compartmental transport model of microbicide delivery by an intravaginal ring

PubMed Central

Geonnotti, Anthony R.; Katz, David F.

2010-01-01

Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 hours following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds. PMID:20222027

Cardiac Arrest during Hospitalization for Delivery in the United States, 1998–2011

PubMed Central

Mhyre, Jill M.; Tsen, Lawrence C.; Einav, Sharon; Kuklina, Elena V.; Leffert, Lisa R.; Bateman, Brian T.

2015-01-01

Background The objective of this analysis was to evaluate the frequency, distribution of potential etiologies, and survival rates of maternal cardiopulmonary arrest during the hospitalization for delivery in the United States. Methods By using data from the Nationwide Inpatient Sample during the years 1998 through 2011, the authors obtained weighted estimates of the number of U.S. hospitalizations for delivery complicated by maternal cardiac arrest. Clinical and demographic risk factors, potential etiologies, and outcomes were identified and compared in women with and without cardiac arrest. The authors tested for temporal trends in the occurrence and survival associated with maternal arrest. Results Cardiac arrest complicated 1 in 12,000 or 8.5 per 100,000 hospitalizations for delivery (99% CI, 7.7 to 9.3 per 100,000). The most common potential etiologies of arrest included hemorrhage, heart failure, amniotic fluid embolism, and sepsis. Among patients with cardiac arrest, 58.9% of patients (99% CI, 54.8 to 63.0%) survived to hospital discharge. Conclusions Approximately 1 in 12,000 hospitalizations for delivery is complicated by cardiac arrest, most frequently due to hemorrhage, heart failure, amniotic fluid embolism, or sepsis. Survival depends on the underlying etiology of arrest. PMID:24694844

Piezoelectric control of needle-free transdermal drug delivery.

PubMed

Stachowiak, Jeanne C; von Muhlen, Marcio G; Li, Thomas H; Jalilian, Laleh; Parekh, Sapun H; Fletcher, Daniel A

2007-12-04

Transdermal drug delivery occurs primarily through hypodermic needle injections, which cause pain, require a trained administrator, and may contribute to the spread of disease. With the growing number of pharmaceutical therapies requiring transdermal delivery, an effective, safe, and simple needle-free alternative is needed. We present and characterize a needle-free jet injector that employs a piezoelectric actuator to accelerate a micron-scale stream of fluid (40-130 microm diameter) to velocities sufficient for skin penetration and drug delivery (50-160 m/s). Existing jet injectors, powered by compressed springs and gases, are not widely used due to painful injections and poor reliability in skin penetration depth and dose. In contrast, our device offers electronic control of the actuator expansion rate, resulting in direct control of jet velocity and thus the potential for more precise injections. We apply a simple fluid-dynamic model to predict the device response to actuator expansion. Further, we demonstrate that injection parameters including expelled volume, jet pressure, and penetration depth in soft materials vary with actuator expansion rate, but are highly coupled. Finally, we discuss how electronically-controlled jet injectors may enable the decoupling of injection parameters such as penetration depth and dose, improving the reliability of needle-free transdermal drug delivery.

Lyophilized Silk Fibroin Hydrogels for the Sustained Local Delivery of Therapeutic Monoclonal Antibodies

PubMed Central

Guziewicz, Nicholas; Best, Annie; Perez-Ramirez, Bernardo; Kaplan, David L.

2011-01-01

The development of sustained delivery systems compatible with protein therapeutics continues to be a significant unmet need. A lyophilized silk fibroin hydrogel matrix (lyogel) for the sustained release of pharmaceutically relevant monoclonal antibodies is described. Sonication of silk fibroin prior to antibody incorporation avoids exposing the antibody to the sol-gel transition inducing shear stress. Fourier Transform Infrared (FTIR) analysis showed no change in silk structural composition between hydrogel and lyogel or with increasing silk fibroin concentration. Antibody release from hydrogels occurred rapidly over 10 days regardless of silk concentration. Upon lyophilization, sustained antibody release was observed over 38 days from lyogels containing 6.2% (w/w) silk fibroin and above. In 3.2% (w/w) silk lyogels, antibody release was comparable to hydrogels. Swelling properties of lyogels followed a similar threshold behavior. Lyogels at 3.2% (w/w) silk recovered approximately 90% of their fluid mass upon rehydration, while approximately 50% fluid recovery was observed at 6.2% (w/w) silk and above. Antibody release was primarily governed by hydrophobic/hydrophilic silk-antibody interactions and secondarily altered by the hydration resistance of the lyogel. Hydration resistance was controlled by altering β-sheet (crystalline) density of the matrix. The antibody released from lyogels maintained biological activity. Silk lyogels offer an advantage as a delivery matrix over other hydrogel materials for the slow release of the loaded protein, making lyogels suitable for long-term sustained release applications. PMID:21216004

Innovations for ISS Plug-In Plan (IPiP) Operations

NASA Technical Reports Server (NTRS)

Moore, Kevin D.

2013-01-01

Limited resources and increasing requirements will continue to influence decisions on ISS. The ISS Plug-In Plan (IPiP) supports power and data for utilization, systems, and daily operations through the Electrical Power System (EPS) Secondary Power/Data Subsystem. Given the fluid launch schedule, the focus of the Plug-In Plan has evolved to anticipate future requirements by judicious development and delivery of power supplies, power strips, Alternating Current (AC) power inverters, along with innovative deployment strategies. A partnership of ISS Program Office, Engineering Directorate, Mission Operations, and International Partners poses unique solutions with existing on-board equipment and resources.

Development and parallelization of a direct numerical simulation to study the formation and transport of nanoparticle clusters in a viscous fluid

NASA Astrophysics Data System (ADS)

Sloan, Gregory James

The direct numerical simulation (DNS) offers the most accurate approach to modeling the behavior of a physical system, but carries an enormous computation cost. There exists a need for an accurate DNS to model the coupled solid-fluid system seen in targeted drug delivery (TDD), nanofluid thermal energy storage (TES), as well as other fields where experiments are necessary, but experiment design may be costly. A parallel DNS can greatly reduce the large computation times required, while providing the same results and functionality of the serial counterpart. A D2Q9 lattice Boltzmann method approach was implemented to solve the fluid phase. The use of domain decomposition with message passing interface (MPI) parallelism resulted in an algorithm that exhibits super-linear scaling in testing, which may be attributed to the caching effect. Decreased performance on a per-node basis for a fixed number of processes confirms this observation. A multiscale approach was implemented to model the behavior of nanoparticles submerged in a viscous fluid, and used to examine the mechanisms that promote or inhibit clustering. Parallelization of this model using a masterworker algorithm with MPI gives less-than-linear speedup for a fixed number of particles and varying number of processes. This is due to the inherent inefficiency of the master-worker approach. Lastly, these separate simulations are combined, and two-way coupling is implemented between the solid and fluid.

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

Needleless connectors substantially reduce flow of crystalloid and red blood cells during rapid infusion.

PubMed

Lehn, Robert A; Gross, Jeffrey B; McIsaac, Joseph H; Gipson, Keith E

2015-04-01

Although needleless connectors (NC) are frequently used in the perioperative setting, the potential of modern NCs to slow delivery of IV fluids has not been thoroughly studied. We examined flow characteristics of 5 NC models during pressurized delivery of crystalloid and banked red blood cells from a Level 1 warmer through various IV catheters. Crystalloid flow rates were reduced by 29% to 85% from control in catheters >18 gauge, while red blood cell flow reductions ranged from 22% to 76% in these catheters (all P < 0.0050). We suggest that practitioners consider eliminating NCs when large IV catheters are inserted for rapid fluid administration.

RESOLVE (Regolith & Environmental Science Oxygen & Lunar Volatile Extraction) Project

NASA Technical Reports Server (NTRS)

Parker, Ray; Coan, Mary; Captain, Janine; Cryderman, Kate; Quinn, Jacqueline

2015-01-01

The RESOLVE Project is a lunar prospecting mission whose primary goal is to characterize water and other volatiles in lunar regolith. The Lunar Advanced Volatiles Analysis (LAVA) subsystem is comprised of a fluid subsystem that transports flow to the gas chromatograph - mass spectrometer (GC-MS) instruments that characterize volatiles and the Water Droplet Demonstration (WDD) that will capture and display water condensation in the gas stream. The LAVA Engineering Test Unit (ETU) is undergoing risk reduction testing this summer and fall within a vacuum chamber to understand and characterize component and integrated system performance. Testing of line heaters, printed circuit heaters, pressure transducers, temperature sensors, regulators, and valves in atmospheric and vacuum environments was done. Test procedures were developed to guide experimental tests and test reports to analyze and draw conclusions from the data. In addition, knowledge and experience was gained with preparing a vacuum chamber with fluid and electrical connections. Further testing will include integrated testing of the fluid subsystem with the gas supply system, near-infrared spectrometer for the Surge Tank (NIRST), WDD, Sample Delivery System, and GC-MS in the vacuum chamber. Since LAVA is a scientific subsystem, the near infrared spectrometer and GC-MS instruments will be tested during the ETU testing phase.

Liquid Acquisition Strategies for Exploration Missions: Current Status 2010

NASA Technical Reports Server (NTRS)

Chato, David J.

2010-01-01

NASA is currently developing the propulsion system concepts for human exploration missions to the lunar surface. The propulsion concepts being investigated are considering the use of cryogenic propellants for the low gravity portion of the mission, that is, the lunar transit, lunar orbit insertion, lunar descent and the rendezvous in lunar orbit with a service module after ascent from the lunar surface. These propulsion concepts will require the vapor free delivery of the cryogenic propellants stored in the propulsion tanks to the exploration vehicles main propulsion system (MPS) engines and reaction control system (RCS) engines. Propellant management devices (PMD s) such as screen channel capillary liquid acquisition devices (LAD s), vanes and sponges currently are used for earth storable propellants in the Space Shuttle Orbiter OMS and RCS applications and spacecraft propulsion applications but only very limited propellant management capability exists for cryogenic propellants. NASA has begun a technology program to develop LAD cryogenic fluid management (CFM) technology through a government in-house ground test program of accurately measuring the bubble point delta-pressure for typical screen samples using LO2, LN2, LH2 and LCH4 as test fluids at various fluid temperatures and pressures. This presentation will document the CFM project s progress to date in concept designs, as well ground testing results.

Transport across the choroid plexus epithelium.

PubMed

Praetorius, Jeppe; Damkier, Helle Hasager

2017-06-01

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

Dental therapeutic systems.

PubMed

Iqbal, Zeenat; Jain, Nilu; Jain, Gaurav K; Talegaonkar, Sushama; Ahuja, Alka; Khar, Roop K; Ahmad, Farhan J

2008-01-01

The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in the current manuscript.

The blood-brain barrier and nasal drug delivery to the central nervous system.

PubMed

Miyake, Marcel Menon; Bleier, Benjamin S

2015-01-01

The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. The objective of this study is to generally review these strategies of drug administration to the CNS. Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

A Comparison of Aerosolization and Homogenization Techniques for Production of Alginate Microparticles for Delivery of Corticosteroids to the Colon.

PubMed

Samak, Yassmin O; El Massik, Magda; Coombes, Allan G A

2017-01-01

Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl 2 crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion into blank microparticles or by direct encapsulation. Homogenization method produced smaller microparticles (45-50 μm), compared to aerosolization (65-90 μm). High drug loadings (40% wt/wt) were obtained for diffusion-loaded aerosolized microparticles. Aerosolized microparticles suppressed drug release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) prior to drug release in simulated colonic fluid (SCF) to a higher extent than homogenized microparticles. Microparticles prepared using aerosolization or homogenization (1 M CaCl 2 , diffusion loaded) released 5% and 17% of drug content after 2 h in SGF and 4 h in SIF, respectively, and 75% after 12 h in SCF. Thus, aerosolization and homogenization techniques show potential for producing alginate microparticles for colonic drug delivery in the treatment of inflammatory bowel disease. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Maternal Azithromycin Therapy for Ureaplasma Intra-Amniotic Infection Delays Preterm Delivery and Reduces Fetal Lung Injury in a Primate Model

PubMed Central

Grigsby, Peta L.; Novy, Miles J.; Sadowsky, Drew W.; Morgan, Terry K.; Long, Mary; Acosta, Ed; Duffy, Lynn B; Waites, Ken B.

2012-01-01

Objective We assessed the efficacy of a maternal multi–dose azithromycin (AZI) regimen, with and without anti–inflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intra–amniotic infection (IAI). Study Design Long–term catheterized rhesus monkeys (n=16) received intra–amniotic inoculation of U. parvum (107 CFU/ml, serovar 1). After contraction onset, rhesus monkeys received either no treatment (n=6); AZI (12.5mg/kg, q12h, IV for 10 days; n=5); or AZI plus dexamethasone (DEX) and indomethacin (INDO; n=5). Outcomes included amniotic fluid pro–inflammatory mediators, U. parvum cultures & PCR, AZI pharmacokinetics and the extent of fetal lung inflammation. Results Maternal AZI therapy eradicated U. parvum IAI from the amniotic fluid within 4 days. Placenta and fetal tissues were 90% culture negative at delivery. AZI therapy significantly delayed preterm delivery and prevented advanced fetal lung injury, although residual acute chorioamnionitis persisted. Conclusions Specific maternal antibiotic therapy can eradicate U. parvum from the amniotic fluid and key fetal organs, with subsequent prolongation of pregnancy which provides a therapeutic window of opportunity to effectively reduce the severity of fetal lung injury. PMID:23111115

A multi-center randomized trial of two different intravenous fluids during labor

PubMed Central

DAPUZZO-ARGIRIOU, Lisa M.; SMULIAN, John C.; ROCHON, Meredith L.; GALDI, Luisa; KISSLING, Jessika M.; SCHNATZ, Peter F.; RIOS, Angel GONZALEZ; AIROLDI, James; CARRILLO, Mary Anne; MAINES, Jaimie; KUNSELMAN, Allen R.; REPKE, John; LEGRO, Richard S.

2017-01-01

Objective To determine if the intrapartum use of a 5% glucose-containing intravenous solution decreases the chance of a cesarean delivery for women presenting in active labor. Methods This was a multi-center, prospective, single (patient) blind, randomized study design implemented at 4 obstetric residency programs in Pennsylvania. Singleton, term, consenting women presenting in active spontaneous labor with a cervical dilation of <6cm were randomized to lactated Ringer's with or without 5% glucose (LR versus D5LR) as their maintenance intravenous fluid. The primary outcome was the cesarean birth rate. Secondary outcomes included labor characteristics, as well as maternal or neonatal complications. Results There were 309 women analyzed. Demographic variables and admitting cervical dilation were similar among study groups. There was no significant difference in the cesarean delivery rate for the D5LR group (23/153 or 15.0%) versus the LR arm (18/156 or 11.5%), [RR (95%CI) of 1.32 (0.75, 2.35), P=0.34]. There were no differences in augmentation rates or intrapartum complications. Conclusions The use of intravenous fluid containing 5% dextrose does not lower the chance of cesarean delivery for women admitted in active labor. PMID:25758624

Time-reversal acoustics and ultrasound-assisted convection-enhanced drug delivery to the brain.

PubMed

Olbricht, William; Sistla, Manjari; Ghandi, Gaurav; Lewis, George; Sarvazyan, Armen

2013-08-01

Time-reversal acoustics is an effective way of focusing ultrasound deep inside heterogeneous media such as biological tissues. Convection-enhanced delivery is a method of delivering drugs into the brain by infusing them directly into the brain interstitium. These two technologies are combined in a focusing system that uses a "smart needle" to simultaneously infuse fluid into the brain and provide the necessary feedback for focusing ultrasound using time-reversal acoustics. The effects of time-reversal acoustics-focused ultrasound on the spatial distribution of infused low- and high-molecular weight tracer molecules are examined in live, anesthetized rats. Results show that exposing the rat brain to focused ultrasound significantly increases the penetration of infused compounds into the brain. The addition of stabilized microbubbles enhances the effect of ultrasound exposure.

Recent Progress of Microfluidics in Translational Applications.

PubMed

Liu, Zongbin; Han, Xin; Qin, Lidong

2016-04-20

Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sonophoresis for Rapid Assessment of Interstitial Fluid and Drug Delivery

DTIC Science & Technology

2007-10-01

sensitive indicator of local diseases, for example skin cancer, psoriasis and eczema , but also of certain systemic diseases such as cardiovascular disease...cytokine " functionality -map" that precisely represents skin’s specific diseased milieu (Fig. 2b-CI and Fig. 3a-AD and PS, 3 additional data in. Supp...yielded a unique cytokine " functionality map", which correlates with the specific diseased state (figure 2d and 3a). A striking, rapid upregulation was

sts128-s-047

NASA Image and Video Library

2009-09-14

STS128-S-047 (11 Sept. 2009) --- Space Shuttle Discovery?s main landing gear touches down at NASA's Dryden Flight Research Center at Edwards Air Force Base in California, concluding a successful mission to the International Space Station. Onboard are NASA astronauts Rick Sturckow, commander; Kevin Ford, pilot; John ?Danny? Olivas, Patrick Forrester, Jose Hernandez and Tim Kopra, all mission specialists; along with European Space Agency astronaut Christer Fuglesang, mission specialist. Discovery landed at 5:53 p.m. (PDT) on Sept. 11, 2009 to end the STS-128 mission, completing its almost 14-day journey of more than 5.7 million miles in space. The landing was diverted to California due to marginal weather at the Kennedy Space Center. Discovery?s mission featured three spacewalks and the delivery of two refrigerator-sized science racks to the space station. One rack will be used to conduct experiments on materials such as metals, glasses and ceramics. The results from these experiments could lead to the development of better materials on Earth. The other rack will be used for fluid physics research. Understanding how fluids react in microgravity could lead to improved designs for fuel tanks, water systems and other fluid-based systems.

sts128-s-045

NASA Image and Video Library

2009-09-11

STS128-S-045 (11 Sept. 2009) --- Space Shuttle Discovery?s main landing gear touches down at NASA's Dryden Flight Research Center at Edwards Air Force Base in California, concluding a successful mission to the International Space Station. Onboard are NASA astronauts Rick Sturckow, commander; Kevin Ford, pilot; John ?Danny? Olivas, Patrick Forrester, Jose Hernandez and Tim Kopra, all mission specialists; along with European Space Agency astronaut Christer Fuglesang, mission specialist. Discovery landed at 5:53 p.m. (PDT) on Sept. 11, 2009 to end the STS-128 mission, completing its almost 14-day journey of more than 5.7 million miles in space. The landing was diverted to California due to marginal weather at the Kennedy Space Center. Discovery?s mission featured three spacewalks and the delivery of two refrigerator-sized science racks to the space station. One rack will be used to conduct experiments on materials such as metals, glasses and ceramics. The results from these experiments could lead to the development of better materials on Earth. The other rack will be used for fluid physics research. Understanding how fluids react in microgravity could lead to improved designs for fuel tanks, water systems and other fluid-based systems.

sts128-s-048

NASA Image and Video Library

2009-09-11

STS128-S-048 (11 Sept. 2009) --- With its drag chute deployed, Space Shuttle Discovery slows to a stop after landing at NASA's Dryden Flight Research Center at Edwards Air Force Base in California, concluding a successful mission to the International Space Station. Onboard are NASA astronauts Rick Sturckow, commander; Kevin Ford, pilot; John ?Danny? Olivas, Patrick Forrester, Jose Hernandez and Tim Kopra, all mission specialists; along with European Space Agency astronaut Christer Fuglesang, mission specialist. Discovery landed at 5:53 p.m. (PDT) on Sept. 11, 2009 to end the STS-128 mission, completing its almost 14-day journey of more than 5.7 million miles in space. The landing was diverted to California due to marginal weather at the Kennedy Space Center. Discovery?s mission featured three spacewalks and the delivery of two refrigerator-sized science racks to the space station. One rack will be used to conduct experiments on materials such as metals, glasses and ceramics. The results from these experiments could lead to the development of better materials on Earth. The other rack will be used for fluid physics research. Understanding how fluids react in microgravity could lead to improved designs for fuel tanks, water systems and other fluid-based systems.

sts128-s-046

NASA Image and Video Library

2009-09-11

STS128-S-046 (11 Sept. 2009) --- Space Shuttle Discovery?s main landing gear touches down at NASA's Dryden Flight Research Center at Edwards Air Force Base in California, concluding a successful mission to the International Space Station. Onboard are NASA astronauts Rick Sturckow, commander; Kevin Ford, pilot; John ?Danny? Olivas, Patrick Forrester, Jose Hernandez and Tim Kopra, all mission specialists; along with European Space Agency astronaut Christer Fuglesang, mission specialist. Discovery landed at 5:53 p.m. (PDT) on Sept. 11, 2009 to end the STS-128 mission, completing its almost 14-day journey of more than 5.7 million miles in space. The landing was diverted to California due to marginal weather at the Kennedy Space Center. Discovery?s mission featured three spacewalks and the delivery of two refrigerator-sized science racks to the space station. One rack will be used to conduct experiments on materials such as metals, glasses and ceramics. The results from these experiments could lead to the development of better materials on Earth. The other rack will be used for fluid physics research. Understanding how fluids react in microgravity could lead to improved designs for fuel tanks, water systems and other fluid-based systems.

CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

PubMed

Dal Monte, Olga; Noble, Pamela L; Turchi, Janita; Cummins, Alex; Averbeck, Bruno B

2014-01-01

Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

Physics Simulation Software for Autonomous Propellant Loading and Gas House Autonomous System Monitoring

NASA Technical Reports Server (NTRS)

Regalado Reyes, Bjorn Constant

2015-01-01

1. Kennedy Space Center (KSC) is developing a mobile launching system with autonomous propellant loading capabilities for liquid-fueled rockets. An autonomous system will be responsible for monitoring and controlling the storage, loading and transferring of cryogenic propellants. The Physics Simulation Software will reproduce the sensor data seen during the delivery of cryogenic fluids including valve positions, pressures, temperatures and flow rates. The simulator will provide insight into the functionality of the propellant systems and demonstrate the effects of potential faults. This will provide verification of the communications protocols and the autonomous system control. 2. The High Pressure Gas Facility (HPGF) stores and distributes hydrogen, nitrogen, helium and high pressure air. The hydrogen and nitrogen are stored in cryogenic liquid state. The cryogenic fluids pose several hazards to operators and the storage and transfer equipment. Constant monitoring of pressures, temperatures and flow rates are required in order to maintain the safety of personnel and equipment during the handling and storage of these commodities. The Gas House Autonomous System Monitoring software will be responsible for constantly observing and recording sensor data, identifying and predicting faults and relaying hazard and operational information to the operators.

Mounting Pressure in the Microenvironment: Fluids, Solids, and Cells in Pancreatic Ductal Adenocarcinoma.

PubMed

DuFort, Christopher C; DelGiorno, Kathleen E; Hingorani, Sunil R

2016-06-01

The microenvironment influences the pathogenesis of solid tumors and plays an outsized role in some. Our understanding of the stromal response to cancers, particularly pancreatic ductal adenocarcinoma, has evolved from that of host defense to tumor offense. We know that most, although not all, of the factors and processes in the microenvironment support tumor epithelial cells. This reappraisal of the roles of stromal elements has also revealed potential vulnerabilities and therapeutic opportunities to exploit. The high concentration in the stroma of the glycosaminoglycan hyaluronan, together with the large gel-fluid phase and pressures it generates, were recently identified as primary sources of treatment resistance in pancreas cancer. Whereas the relatively minor role of free interstitial fluid in the fluid mechanics and perfusion of tumors has been long appreciated, the less mobile, gel-fluid phase has been largely ignored for historical and technical reasons. The inability of classic methods of fluid pressure measurement to capture the gel-fluid phase, together with a dependence on xenograft and allograft systems that inaccurately model tumor vascular biology, has led to an undue emphasis on the role of free fluid in impeding perfusion and drug delivery and an almost complete oversight of the predominant role of the gel-fluid phase. We propose that a hyaluronan-rich, relatively immobile gel-fluid phase induces vascular collapse and hypoperfusion as a primary mechanism of treatment resistance in pancreas cancers. Similar properties may be operant in other solid tumors as well, so revisiting and characterizing fluid mechanics with modern techniques in other autochthonous cancers may be warranted. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Fluid mechanics in the perivascular space.

PubMed

Wang, Peng; Olbricht, William L

2011-04-07

Perivascular space (PVS) within the brain is an important pathway for interstitial fluid (ISF) and solute transport. Fluid flowing in the PVS can affect these transport processes and has significant impacts on physiology. In this paper, we carry out a theoretical analysis to investigate the fluid mechanics in the PVS. With certain assumptions and approximations, we are able to find an analytical solution to the problem. We discuss the physical meanings of the solution and particularly examine the consequences of the induced fluid flow in the context of convection-enhanced delivery (CED). We conclude that peristaltic motions of the blood vessel walls can facilitate fluid and solute transport in the PVS. Copyright © 2011 Elsevier Ltd. All rights reserved.

The properties of an improvised piston pump for the rapid delivery of intravenous fluids.

PubMed

Smart, C M; Primrose, C W; Peters, A L; Speirits, E J

2014-02-01

To maximise the effect of a small fluid load, it is occasionally desirable to bolus manually with multiple depressions of a large-capacity syringe. This is usually achieved by placing the syringe on the side port of a three-way tap. We modified this technique by placing two-one-way valves in line with the three-way tap, effectively creating a piston pump, the infusion rates via which we compared with those achieved by an inflatable pressure-infuser in a simulated resuscitation. Fluid flow was faster using the piston pump than with the pressure-infuser (mean (SD) time to infuse 2000 ml saline 0.9% via a 16-G cannula 352 (10) s vs 495 (19) s, respectively, p < 0.0001). The piston pump appears to have potential for both tight control of fluid delivery and major high-volume resuscitation. The lightweight nature of the pump and its lack of reliance on gravity may also make it suitable for the pre-hospital setting. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Role of intrapartum transcervical amnioinfusion in patients with meconium-stained amniotic fluid.

PubMed

Bhatia, Pushpa; Reena, Kumari; Nangia, Sangita

2013-03-01

The study was undertaken to evaluate maternal, perinatal outcomes following transcervical intrapartum amnioinfusion in women with meconium-stained amniotic fluid. A prospective comparative study was conducted on 100 women with meconium-stained amniotic fluid in labor. Group A: study group (50 cases) received amnioinfusion. Group B: control group (50 cases) did not receive amnioinfusion. FHR monitoring was done using cardiotocography. Significant relief from variable decelerations was seen in 68.18 % cases in the amnioinfusion group as compared to 7.1 % cases in the control group. 78 % cases who were given amnioinfusion had vaginal delivery as compared to 18 % cases in the control group. Fourteen percent cases in the study group had cesarean delivery as compared to 68 % cases in the control group. Meconium aspiration syndrome was seen in six percent neonates in the study group as compared to 20 % in the control group. Two neonates died in the control group due to meconium aspiration syndrome. There was no maternal mortality or major maternal complication. Intrapartum transcervical amnioinfusion is valuable in patients with meconium-stained amniotic fluid.

Multidisciplinary management of placenta percreta complicated by embolic phenomena.

PubMed

Styron, A G; George, R B; Allen, T K; Peterson-Layne, C; Muir, H A

2008-07-01

Hemorrhage and thrombosis are major causes of maternal mortality. This case discusses the management of a woman with placenta percreta complicated by intraoperative pulmonary embolism. A 39-year-old gravida 3 with two previous cesarean deliveries presented at 34 weeks of gestation with an antepartum hemorrhage. Magnetic resonance imaging confirmed placenta percreta. The multidisciplinary group including obstetricians, gynecological oncologists, interventional radiologists and anesthesiologists developed a delivery plan. Cesarean delivery was performed with internal iliac artery occlusion and embolization catheters in place. After the uterine incision our patient experienced acute hypotension and hypoxia associated with a drop in the end-tidal carbon dioxide and sinus tachycardia. She was resuscitated and the uterus closed with the placenta in situ. Postoperatively, uterine bleeding was arrested by immediate uterine artery embolization. With initiation of embolization, hypotension and hypoxia recurred. Oxygenation and hemodynamics slowly improved, the case continued and the patient was extubated uneventfully at the end of the procedure. Computed tomography revealed multiple pulmonary emboli. The patient was anticoagulated with low-molecular-weight heparin and returned six weeks later for hysterectomy. Placenta percreta with invasion into the bladder can be catastrophic if not recognized before delivery. The chronology of events suggests that this may have been amniotic fluid emboli. An intact placenta with abnormal architecture, such as placenta percreta, may increase the risk of amniotic fluid embolus. The clinical findings and co-existing filling defects on computed tomography may represent a spectrum of amniotic fluid embolism syndrome.

Influence of lactoferrin in preventing preterm delivery: a pilot study.

PubMed

Giunta, Giuliana; Giuffrida, Lorena; Mangano, Katia; Fagone, Paolo; Cianci, Antonio

2012-01-01

Lactoferrin (Lf) is an approximately 80-kDa iron-binding glycoprotein, belonging to the transferrin family, with well-known bacteriostatic and bactericidal properties. It is produced and stored in specific (secondary) neutrophil granules and released during neutrophil activation and degranulation. Nowadays, Lf has a well-known therapeutic indication for combating iron deficiency anemia (IDA) in pregnant women. Studies suggest that Lf plays an important role against cervicovaginal infections by decreasing cytokines levels, such as interleukin (IL)-6, in cervicovaginal fluid. The aim of this preliminary trial was to evaluate the effectiveness of Lf in preventing preterm delivery caused by cervical infections and ripening. From November 2009 to August 2010, 21 pregnant women (26-32 weeks pregnant), aged between 22 and 36 years, suffering from IDA, at risk of preterm delivery, were prospectively enrolled in the study. One group (N=14) received 100 mg of recombinant human lactoferrin (bLf) [corrected] (lattoferrina; AG-pharma) twice a day before meals, for one month. The other group (N=7) received 520 mg of ferrous sulfate (Ferro-Grad; Abbott Laboratories, USA) once a day. The patients underwent transvaginal ultrasound to evaluate cervical length and funneling, and vaginal swabs were used to detect infections and cervicovaginal fluid sample collection to determine IL-6 levels. The results showed a correlation between the oral administration of 200 mg of bLf [corrected] with both the normalization of vaginal flora (vaginal infection disappearance) and the decrease in IL-6 cervicovaginal fluid levels in women at risk of preterm delivery.

Borderline amniotic fluid index and perinatal outcomes in the uncomplicated term pregnancy.

PubMed

Choi, Soo Ran

2016-01-01

To determine perinatal outcomes in uncomplicated term pregnancies with a borderline amniotic fluid index (AFI). A retrospective review was conducted of uncomplicated singleton pregnancies at term (>37 weeks). Borderline and normal AFI were defined as 5.1 ≤ AFI ≤ 8.0 cm and 8.1 ≤ AFI ≤ 24 cm, respectively. Adverse perinatal outcomes, cesarean delivery for non-reassuring fetal heart rate testing, meconium-stained amniotic fluid, a 5-min Apgar score of <7, admission to the neonatal intensive care unit (NICU), and whether the neonate was small for gestational age were compared between the borderline and normal AFI groups. Borderline AFI was not significantly associated with cesarean delivery for non-reassuring fetal heart rate testing (p = 0.513), meconium-stained amniotic fluid (p = 0.641), admission to the NICU (p = 0.368), or a 5-min Apgar score of <7 (p = 1.00). However, the number of neonates who were small for gestational age (p = 0.021) and rates of induction of labor (p < 0.001) were significantly higher in the borderline group. Multiple logistic regression analysis showed that borderline AFI was not associated with cesarean delivery for non-reassuring fetal heart rate testing (odds ratio [OR] = 0.72, 95% confidence interval [CI] 0.27-1.91, p = 0.52). In uncomplicated term pregnancies, a borderline AFI does not increase the risk of adverse perinatal outcomes.

A gastro-resistant ovalbumin bi-layered mini-tablet-in-tablet system for the delivery of Lactobacillus acidophilus probiotic to simulated human intestinal and colon conditions.

PubMed

Govender, Mershen; Choonara, Yahya Essop; van Vuuren, Sandy; Kumar, Pradeep; du Toit, Lisa Claire; Pillay, Viness

2015-07-01

The viability of probiotic bacteria during formulation processes and delivery is vital to ensure health benefits. This study focuses on the use of gastro-resistant denatured ovalbumin for the targeted delivery of probiotic Lactobacillus acidophilus to simulated human intestinal and colon conditions through a bi-layered mini-tablet-in-tablet system (BMTTS). The BMTTS consists of two gastro-resistant ovalbumin mini-tablets containing L. acidophilus suspended in lactose and eudragit S100 for targeted intestinal and colonic delivery respectively. Luminescence has been utilized to ensure probiotic viability during formulation processes in addition to determining all probiotic release profiles. The mechanism of probiotic release from the ovalbumin matrix was ascertained using mathematical modelling and molecular docking studies. Magnetic resonance imaging and differential scanning calorimetry are also included as part of the in-vitro characterization of the ovalbumin system. The BMTTS was effective in the delivery of L. acidophilus to simulated human intestinal and colon conditions. Formulation processes were furthermore determined to maintain probiotic viability. Statistical analysis of the release data noted a significant effect of pH denaturation on the release properties of ovalbumin. Magnetic resonance imaging results have indicated a decrease in ovalbumin matrix size upon exposure to simulated intestinal fluid. Molecular docking studies carried out depicted the interaction and binding positions inherent to the ovalbumin-pancreatic trypsin interaction complex indicating the possible enzymatic degradation of ovalbumin leading to the release of the probiotic from the protein matrix. The BMTTS has been determined to be effective in the protection and delivery of probiotic L. acidophilus to simulated human intestinal and colonic conditions. Molecular docking analysis has noted that pancreatin exerts a significant effect on probiotic release from the gastro-resistant ovalbumin matrix. © 2015 Royal Pharmaceutical Society.

Intrathecal delivery of protein therapeutics to the brain: a critical reassessment.

PubMed

Calias, Pericles; Banks, William A; Begley, David; Scarpa, Maurizio; Dickson, Patricia

2014-11-01

Disorders of the central nervous system (CNS), including stroke, neurodegenerative diseases, and brain tumors, are the world's leading causes of disability. Delivery of drugs to the CNS is complicated by the blood-brain barriers that protect the brain from the unregulated leakage and entry of substances, including proteins, from the blood. Yet proteins represent one of the most promising classes of therapeutics for the treatment of CNS diseases. Many strategies for overcoming these obstacles are in development, but the relatively straightforward approach of bypassing these barriers through direct intrathecal administration has been largely overlooked. Originally discounted because of its lack of usefulness for delivering small, lipid-soluble drugs to the brain, the intrathecal route has emerged as a useful, in some cases perhaps the ideal, route of administration for certain therapeutic protein and targeted disease combinations. Here, we review blood-brain barrier functions and cerebrospinal fluid dynamics and their relevance to drug delivery via the intrathecal route, discuss animal and human studies that have investigated intrathecal delivery of protein therapeutics, and outline several characteristics of protein therapeutics that can allow them to be successfully delivered intrathecally. Copyright © 2014 Elsevier Inc. All rights reserved.

Pulsed-High Intensity Focused Ultrasound (HIFU) Exposures for Enhanced Delivery of Therapeutics: Mechanisms and Applications

NASA Astrophysics Data System (ADS)

Frenkel, Victor; Deng, Cheri; O'Neill, Brian E.; Quijano, Jade; Stone, Michael J.; Dromi, Sergio; Hunter, Finie; Xie, Jianwu; Quinn, Timothy P.; Wood, Bradford J.; Li, King C. P.

2006-05-01

The majority of focused ultrasound applications today involve long, continuous exposures that produce significant temperature elevations for tissue ablation and irreversible coagulative necrosis. Comparatively little has been done with non-continuous (or, pulsed) exposures that can produce primarily mechanical effects with only minimal heat. Our investigations have shown that pulsed-HIFU exposures can non-invasively and non-destructively enhance the delivery of both systemically and locally injected materials (e.g. imaging agents, optical probes, and plasmid DNA) in both normal and cancerous tissues. It is hypothesized that the enhancing effects are directly linked to tissue displacement from locally-generated radiation forces. In normal tissue, it is thought that shear forces are produced between adjacent tissue regions experiencing non-uniform displacement. The resulting strain opens cellular junctions in both the vasculature and the parenchyma, increasing extravasation and interstitial diffusion, respectively. In solid tumors, improved delivery is thought to also be related to both an increase in fluid exchange that leads to decreased interstitial pressure, and disruptions of fibrillar collagen in the extracellular matrix. Preliminary experiments are presented that were carried out to help elucidate the mechanisms by which enhanced delivery was achieved, and possible directions for future investigations are discussed.

Central online hemodiafiltration in Japan: management of water quality and practice.

PubMed

Yamashita, Akihiro C; Sato, Takashi

2009-01-01

Hemodiafiltration (HDF) includes a variety of technologies and preparation of ultrapure dialysis fluid has made it possible to perform online HDF and its extensive alternatives. According to current statistics, 5.8% of ESRD patients are treated with HDF in Japan. The majority of these HDF treatments are performed using the central dialysis fluid delivery system (CDDS), this is because most Japanese clinicians and researchers consider that with CDDS it is easier to prepare substitution fluid; moreover, CDDS has economical advantages against single-patient dialysis machine (SPDM)-based counterparts. The water quality at each patient station (dialysis console) is regularly validated by bacterial culture (colony-forming units) and by measuring endotoxin concentration (ET). Since ET measurement takes much less time than bacterial culture, ET is often used as an indicator to verify the water quality for online use. Dialysis fluid with ET below the detection level (usually <0.001 EU/ml) is used for online substitution. In CDDS online HDF, since dialysis clinics must prepare not only the dialysis fluid but also the substitution fluid, they need to satisfy almost the same requirements as pharmaceutical water treatment factories do. The Japanese Society for Dialysis Therapy (JSDT) together with the Japanese Society for Hemodiafiltration (JS-HDF) is now preparing guidelines to meet all these necessary requirements on a worldwide basis. (c) 2009 S. Karger AG, Basel.

LyP-1 ultrasonic microbubbles targeting to cancer cell as tumor bio-acoustics markers or drug carriers: targeting efficiency evaluation in, microfluidic channels.

PubMed

Li, Xiang; Jin, Qiaofeng; Chen, Tan; Zhang, Baoyue; Zheng, Rongqin; Wang, Zhanhui; Zheng, Hairong

2009-01-01

Using ultrasonic contrast microbubbles as acoustic biomarkers and drug carrier vehicles by conjugating tumor specific antibody to microbubbles has shown great potential in ultrasonic tumor molecular imaging or drug-delivery and therapy. Microbubble probe targeting efficiency is one of the major challenges. In this study, we developed a novel method to evaluate the targeting capability and efficiency of microbubbles to cells, and more specifically, microbubbles binding LyP-1 (a cyclic nonapeptide acid peptide) target to cancer cell within a microfluidic system. The micro cell sieves within the microfludic channels could trap the tumor cells and enhance the microbubble's interaction with the cell. Assisted with the controllable fluid shear stress, the microbubble's targeting to the cell and the corresponding affinity efficiency could be quantitatively evaluated under a florescent microscope. The system provides a useful low-cost high efficient in vitro platform for studying microbubble-cell interaction for ultrasonic tumor molecular imaging or drug-delivery and therapy.

In vitro chlorhexidine release from alginate based microbeads for periodontal therapy

PubMed Central

Reske, Thomas; Böhmer, Femke; Hornung, Anne; Grabow, Niels; Lang, Hermann

2017-01-01

Periodontitis is one of the most common infectious diseases globally that, if untreated, leads to destruction of the tooth supporting tissues and finally results in tooth loss. Evidence shows that standard procedures as mechanical root cleaning could be supported by further treatment options such as locally applied substances. Due to gingival crevicular fluid flow, substances are commonly washed out off the periodontal pockets. The evaluation of administration techniques and the development of local drug releasing devices is thus an important aspect in periodontal research. This study describes the development and examination of a new alginate based, biodegradable and easily applicable drug delivery system for chlorhexidine (CHX). Different micro beads were produced and loaded with CHX and the release profiles were investigated by high performance liquid chromatography (HPLC). The in vitro-demonstrated release of CHX from alginate based beads shows comparable releasing characteristics as clinically approved systems. Yet many characteristics of this new delivery system show to be favourable for periodontal therapy. Easy application by injection, low production costs and multifunctional adaptions to patient related specifics may improve the usage in routine care. PMID:28973028

Monitoring nicotine intake from e-cigarettes: measurement of parent drug and metabolites in oral fluid and plasma.

PubMed

Papaseit, Esther; Farré, Magí; Graziano, Silvia; Pacifici, Roberta; Pérez-Mañá, Clara; García-Algar, Oscar; Pichini, Simona

2017-03-01

Electronic cigarettes (e-cig) known as electronic nicotine devices recently gained popularity among smokers. Despite many studies investigating their safety and toxicity, few examined the delivery of e-cig-derived nicotine and its metabolites in alternative biological fluids. We performed a randomized, crossover, and controlled clinical trial in nine healthy smokers. Nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (3-HCOT) were measured in plasma and oral fluid by liquid chromatography-tandem mass spectrometry after consumption of two consecutive e-cig administrations or two consecutive tobacco cigarettes. NIC and its metabolites were detected both in oral fluid and plasma following both administration conditions. Concentrations in oral fluid resulted various orders of magnitude higher than those observed in plasma. Oral fluid concentration of tobacco cigarette and e-cig-derived NIC peaked at 15 min after each administration and ranged between 1.0 and 1396 μg/L and from 0.3 to 860 μg/L; those of COT between 52.8 and 110 μg/L and from 33.8 to 94.7 μg/L; and those of 3-HCOT between 12.4 and 23.5 μg/L and from 8.5 to 24.4 μg/L. The oral fluid to plasma concentration ratio of both e-cig- and tobacco cigarette-derived NIC peaked at 15 min after both administrations and correlated with oral fluid NIC concentration. The obtained results support the measurement of NIC and metabolites in oral fluid in the assessment of intake after e-cig use and appear to be a suitable alternative to plasma when monitoring nicotine delivery from e-cig for clinical and toxicological studies.

Colon targeted delivery systems of metronidazole based on osmotic technology: development and evaluation.

PubMed

Kumar, Pramod; Singh, Sanjay; Mishra, Brahmeshwar

2008-09-01

Colon targeted delivery systems of metronidazole (MTZ) based on osmotic technology were developed. The developed systems consisted of osmotic core (drug, osmotic agent and wicking agent), coated with semipermeable membrane (SPM) containing guar gum as pore former, coated core were then further coated with enteric coating to protect the system from acidic environment of stomach. The effect of various formulation variables namely the level of wicking agent (sodium lauryl sulphate), osmotic agent in the osmotic core, the level of pore former (guar gum) in SPM, and the thickness of SPM, were studied on physical parameters and drug release characteristics of developed formulations. MTZ release was inversely proportional to SPM thickness, but directly related to the level of pore former, wicking agent and osmotic agent. On the other hand burst strength of the exhausted shells was decreased with the increase in level of pore former in the membrane but increased with the increase in the thickness of SPM. The drug release from the developed formulations was independent of pH, and agitation intensity, but dependent on the osmotic pressure of the release media. The thickness of enteric coating could prevent formation of delivery pores before contact with simulated colonic fluid, but had no effect on drug release. Result of SEM studies showed the formation of in-situ delivery pores in the membrane from where the drug release occurred, and the number of pores formed were directly related to the initial level of pore former (guar gum) in SPM. The manufacturing procedure was found to be reproducible and formulations were found to be stable during 3 months of accelerated stability studies.

Open Source Tools for Temporally Controlled Rodent Behavior Suitable for Electrophysiology and Optogenetic Manipulations

PubMed Central

Solari, Nicola; Sviatkó, Katalin; Laszlovszky, Tamás; Hegedüs, Panna; Hangya, Balázs

2018-01-01

Understanding how the brain controls behavior requires observing and manipulating neural activity in awake behaving animals. Neuronal firing is timed at millisecond precision. Therefore, to decipher temporal coding, it is necessary to monitor and control animal behavior at the same level of temporal accuracy. However, it is technically challenging to deliver sensory stimuli and reinforcers as well as to read the behavioral responses they elicit with millisecond precision. Presently available commercial systems often excel in specific aspects of behavior control, but they do not provide a customizable environment allowing flexible experimental design while maintaining high standards for temporal control necessary for interpreting neuronal activity. Moreover, delay measurements of stimulus and reinforcement delivery are largely unavailable. We combined microcontroller-based behavior control with a sound delivery system for playing complex acoustic stimuli, fast solenoid valves for precisely timed reinforcement delivery and a custom-built sound attenuated chamber using high-end industrial insulation materials. Together this setup provides a physical environment to train head-fixed animals, enables calibrated sound stimuli and precisely timed fluid and air puff presentation as reinforcers. We provide latency measurements for stimulus and reinforcement delivery and an algorithm to perform such measurements on other behavior control systems. Combined with electrophysiology and optogenetic manipulations, the millisecond timing accuracy will help interpret temporally precise neural signals and behavioral changes. Additionally, since software and hardware provided here can be readily customized to achieve a large variety of paradigms, these solutions enable an unusually flexible design of rodent behavioral experiments. PMID:29867383

Development and optimization of a self-microemulsifying drug delivery system for atorvastatin calcium by using D-optimal mixture design.

PubMed

Yeom, Dong Woo; Song, Ye Seul; Kim, Sung Rae; Lee, Sang Gon; Kang, Min Hyung; Lee, Sangkil; Choi, Young Wook

2015-01-01

In this study, we developed and optimized a self-microemulsifying drug delivery system (SMEDDS) formulation for improving the dissolution and oral absorption of atorvastatin calcium (ATV), a poorly water-soluble drug. Solubility and emulsification tests were performed to select a suitable combination of oil, surfactant, and cosurfactant. A D-optimal mixture design was used to optimize the concentration of components used in the SMEDDS formulation for achieving excellent physicochemical characteristics, such as small droplet size and high dissolution. The optimized ATV-loaded SMEDDS formulation containing 7.16% Capmul MCM (oil), 48.25% Tween 20 (surfactant), and 44.59% Tetraglycol (cosurfactant) significantly enhanced the dissolution rate of ATV in different types of medium, including simulated intestinal fluid, simulated gastric fluid, and distilled water, compared with ATV suspension. Good agreement was observed between predicted and experimental values for mean droplet size and percentage of the drug released in 15 minutes. Further, pharmacokinetic studies in rats showed that the optimized SMEDDS formulation considerably enhanced the oral absorption of ATV, with 3.4-fold and 4.3-fold increases in the area under the concentration-time curve and time taken to reach peak plasma concentration, respectively, when compared with the ATV suspension. Thus, we successfully developed an optimized ATV-loaded SMEDDS formulation by using the D-optimal mixture design, that could potentially be used for improving the oral absorption of poorly water-soluble drugs.

Development and optimization of a self-microemulsifying drug delivery system for ator vastatin calcium by using d-optimal mixture design

PubMed Central

Yeom, Dong Woo; Song, Ye Seul; Kim, Sung Rae; Lee, Sang Gon; Kang, Min Hyung; Lee, Sangkil; Choi, Young Wook

2015-01-01

In this study, we developed and optimized a self-microemulsifying drug delivery system (SMEDDS) formulation for improving the dissolution and oral absorption of atorvastatin calcium (ATV), a poorly water-soluble drug. Solubility and emulsification tests were performed to select a suitable combination of oil, surfactant, and cosurfactant. A d-optimal mixture design was used to optimize the concentration of components used in the SMEDDS formulation for achieving excellent physicochemical characteristics, such as small droplet size and high dissolution. The optimized ATV-loaded SMEDDS formulation containing 7.16% Capmul MCM (oil), 48.25% Tween 20 (surfactant), and 44.59% Tetraglycol (cosurfactant) significantly enhanced the dissolution rate of ATV in different types of medium, including simulated intestinal fluid, simulated gastric fluid, and distilled water, compared with ATV suspension. Good agreement was observed between predicted and experimental values for mean droplet size and percentage of the drug released in 15 minutes. Further, pharmacokinetic studies in rats showed that the optimized SMEDDS formulation considerably enhanced the oral absorption of ATV, with 3.4-fold and 4.3-fold increases in the area under the concentration-time curve and time taken to reach peak plasma concentration, respectively, when compared with the ATV suspension. Thus, we successfully developed an optimized ATV-loaded SMEDDS formulation by using the d-optimal mixture design, that could potentially be used for improving the oral absorption of poorly water-soluble drugs. PMID:26089663

Microneedle arrays for biosensing and drug delivery

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

Wang, Joseph; Windmiller, Joshua Ray; Narayan, Roger

Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a^ device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce amore » probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.« less

Time-reversal acoustics and ultrasound-assisted convection-enhanced drug delivery to the brain

PubMed Central

Olbricht, William; Sistla, Manjari; Ghandi, Gaurav; Lewis, George; Sarvazyan, Armen

2013-01-01

Time-reversal acoustics is an effective way of focusing ultrasound deep inside heterogeneous media such as biological tissues. Convection-enhanced delivery is a method of delivering drugs into the brain by infusing them directly into the brain interstitium. These two technologies are combined in a focusing system that uses a “smart needle” to simultaneously infuse fluid into the brain and provide the necessary feedback for focusing ultrasound using time-reversal acoustics. The effects of time-reversal acoustics-focused ultrasound on the spatial distribution of infused low- and high-molecular weight tracer molecules are examined in live, anesthetized rats. Results show that exposing the rat brain to focused ultrasound significantly increases the penetration of infused compounds into the brain. The addition of stabilized microbubbles enhances the effect of ultrasound exposure. PMID:23927197

Microneedle arrays for biosensing and drug delivery

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

Wang, Joseph; Windmiller, Joshua Ray; Narayan, Roger

Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce amore » probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.« less

Development of coated nifedipine dry elixir as a long acting oral delivery with bioavailability enhancement.

PubMed

Choi, Jae-Yoon; Jin, Su-Eon; Park, Youmie; Lee, Hyo-Jong; Park, Yohan; Maeng, Han-Joo; Kim, Chong-Kook

2011-10-01

To develop the long acting nifedipine oral delivery with bioavailability enhancement, a nifedipine dry elixir (NDE) containing nifedipine ethanol solution in dextrin shell was prepared using a spray-dryer, and then coated nifedipine dry elixir (CNDE) was prepared by coating NDE with Eudragit acrylic resin. The physical characteristics and bioavailability of NDE and CNDE were evaluated, and then compared to those of nifedipine powder. NDE and CNDE, which were spherical in shape, had about 6.64 and 8.68-8.75 μm of geometric mean diameters, respectively. The amount of nifedipine dissolved from NDE for 60 min increased about 7- and 40-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, respectively. Nifedipine released from CNDE was retarded in both dissolution media compared with that from NDE. After oral administration of NDE, the C(max) and AUC(0→8h) of nifedipine in rat increased about 13- and 7-fold, respectively, and the Tmax of nifedipine was reduced significantly compared with those after oral administration of nifedipine powder alone. The AUC(0→8h) and T(max) of nifedipine in CNDE increased markedly and the C(max) of nifedipine in CNDE was significantly reduced compared to those in NDE. It is concluded that CNDE, which could lower the initial burst-out plasma concentration and maintain the plasma level of nifedipine over a longer period with bioavailability enhancement, might be one of potential alternatives to the marketed long acting oral delivery system for nifedipine.

Polymeric anticancer drugs with pH-controlled activation.

PubMed

Ulbrich, Karel; Subr, Vladimír

2004-04-23

Use of macromolecular water-soluble carriers of anti-cancer drugs represents a promising approach to cancer therapy. Release of drugs from the carrier system is a prerequisite for therapeutic activity of most macromolecular anti-cancer conjugates. Incorporation of acid-sensitive spacers between the drug and carrier enables release of an active drug from the carrier in a tumor tissue, either in slightly acidic extracellular fluids or, after endocytosis, in endosomes or lysosomes of cancer cells. This paper reviews advances in development and study of properties of various acid-sensitive macromolecular drug delivery systems, starting from simple polymer-drug conjugates to ending with site-specific antibody-targeted polymer-drug conjugates.

Plant-based oral delivery of β-glucocerebrosidase as an enzyme replacement therapy for Gaucher's disease.

PubMed

Shaaltiel, Yoseph; Gingis-Velitski, Svetlana; Tzaban, Salit; Fiks, Nadia; Tekoah, Yoram; Aviezer, David

2015-10-01

Gaucher's disease (GD), a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy (ERT) using recombinant GCD that is administered intravenously every 2 weeks. However, intravenous administration includes discomfort or pain and might cause local and systemic infections that may lead to low patient compliance. An orally administered drug has the potential to alleviate these problems. In this study, we describe the potential use of plant cells as a vehicle for the oral delivery of recombinant human GCD (prGCD) expressed in carrot cells. The in vitro results demonstrate that the plant cells protect the recombinant protein in the gastric fluids and may enable absorption into the blood. Feeding experiments, with rat and pig as model animals, using carrot cells containing prGCD, show that active recombinant prGCD was found in the digestive tract and blood system and reached both, liver and spleen, the target organs in GD. These results demonstrate that the oral administration of proteins encapsulated in plant cells is feasible. Specifically, carrot cells containing recombinant human prGCD can be used as an oral delivery system and are a feasible alternative to intravenous administration of ERT for GD. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery

PubMed Central

Nath, Bipul; Nath, Lila Kanta

2013-01-01

The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. PMID:26555985

Biomanufacturing and self-propulsion dynamics of nanoscale bacteria-enabled autonomous delivery systems

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

Traore, Mahama A.; Behkam, Bahareh, E-mail: behkam@vt.edu; School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia 24061

Flagellated bacteria have superb self-propulsion capabilities and are able to effectively move through highly viscous fluid and semi-solid (porous) environments. This innate aptitude has been harvested for whole-cell actuation of bio-hybrid microrobotic systems with applications in directed transport and microassembly. In this work, we present the biomanufacturing of Nanoscale Bacteria-Enabled Autonomous Delivery Systems (NanoBEADS) by controlled self-assembly and investigate the role of nanoparticle load on the dynamics of their self-propulsion in aqueous environments. Each NanoBEADS agent is comprised of spherical polystyrene nanoparticles assembled onto the body of a flagellated Escherichia coli bacterium. We demonstrate that the NanoBEADS assembly configuration ismore » strongly dependent upon the nanoparticles to bacteria ratio. Furthermore, we characterized the stochastic motion of the NanoBEADS as a function of the quantity and size of the nanoparticle load and computationally analyzed the effect of the nanoparticle load on the experienced drag force. We report that the average NanoBEADS swimming speed is reduced to 65% of the free-swimming bacteria speed (31 μm/s) at the highest possible load. NanoBEADS can be utilized as single agents or in a collaborative swarm in order to carry out specific tasks in a wide range of applications ranging from drug delivery to whole cell biosensing.« less

Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety.

PubMed

Modepalli, Naresh; Shivakumar, H Nanjappa; McCrudden, Maeliosa T C; Donnelly, Ryan F; Banga, Ajay; Murthy, S Narasimha

2016-03-01

Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Apparatus and Methods for Fluid Storage and Delivery

NASA Technical Reports Server (NTRS)

Parazynski, Scott E. (Inventor); Bue, Grant C. (Inventor); Urban, Kase C. (Inventor); Schaefbauer, Mark E. (Inventor)

2014-01-01

An apparatus and method for storing and delivering fluid to a person comprises, in at least one specific embodiment, a fluid reservoir having an internal volume therein with an opening disposed through a first wall or a second wall of the fluid reservoir and located toward a first end of the fluid reservoir. A first portion of a tube can be exterior to the fluid reservoir and a second portion of the tube can be disposed through the opening and within the internal volume. At least one insulation layer can be disposed about the exterior of the first wall of the fluid reservoir. The second wall of the fluid reservoir can be configured for transferring heat from or to the internal volume or from the person. At least one baffle is disposed within the internal volume and connected to the first wall and the second wall of the fluid reservoir.

Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections

PubMed Central

W. S. Yapa, Shalini; Li, Jian; Porter, Christopher J. H.; Nation, Roger L.

2013-01-01

Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections. PMID:23917323

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.

Likelihood ratios for the prediction of preterm delivery with biomarkers.

PubMed

Hee, Lene

2011-11-01

To conduct a literature search for selected biomarkers on preterm delivery and estimate their likelihood ratios (LR). Structured review. Low and high-risk populations and women with symptoms of preterm delivery. METHODS. Publications were identified in PubMed. LR on selected biomarkers for preterm delivery. In asymptomatic women with low risk of preterm delivery, the following biomarkers gave major shifts in probability (LR above 5): twins (LR+ 10), Ureaplasma urealyticum in amniotic fluid (LR+ of 10), cervical length <25mm (LR+ 6), salival estriol (LR+ 5) and various combined tests. In asymptomatic women with high risk of preterm delivery, short cervical length (LR+ 11, LR- 0.7), high serum tumor necrosis factor-alpha (LR+ 10, LR- 0.6) gave major shifts in probability. In women with symptoms of preterm delivery, major shifts in probability can be obtained from the following amniotic fluid biomarkers: high matrix metalloproteinase-8 (LR+ 23, LR- 0.6), Ureaplasma urealyticum (LR+ 19, LR- 0.8), high interleukin (IL)-6 (LR+ 9, LR- 0.2), IL-8 (LR+10, LR- 0.2) and tumor necrosis factor-alpha (LR+ 8, LR- 0.4). In serum IL-6 (LR+ 12, LR- 0.2), Cluster of Differentiation 163 (LR+9, LR-0.8) and various combined tests. Vaginal fetal fibronectin (LR+ 3 and LR- 0.5) and short cervical length (LR+ 2, LR- 0.3) gave LRs of some importance (LR below 5). Several biomarkers have been identified for assessment of risk of preterm delivery. Their clinical relevance depends on the efficacy of the interventions which can be offered to these patients. © 2011 The Author Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Increased rates of cesarean sections and large families: a potentially dangerous combination.

PubMed

Saleh, Ahmed M; Dudenhausen, Joachim W; Ahmed, Badreldeen

2017-07-26

Rates of cesarean sections have been on the rise over the past three decades all over the world, despite the ideal rate of 10-15% that had been set by the World Health Organization (WHO) in 1985, in Fortaleza, Brazil. This epidemic increase in the rate of cesarean delivery is due to many factors which include, cesarean delivery on request, advanced maternal age at first pregnancy, decrease in number of patients who are willing to try vaginal birth after cesarean delivery, virtual disappearance of vaginal breech delivery, perceived increase in the weight of the fetus and increase in the number of women with chronic medical conditions such as Diabetes Mellitus and congenital heart disease in the reproductive age. There is no doubt that cesarean delivery is a safe procedure and it is getting safer and safer for many reasons. However, like all other surgical procedures it is not without risks both to the mother and the new born. There is a substantial increase in the incidence of morbidly adherent placenta and the risk of scar pregnancy. In the Middle East and many African and Asian countries women tend to have large families. The number of previous cesarean section deliveries is directly proportional to the risk of developing morbidly adherent placenta. Morbidly adherent placenta is the most common cause of emergency postpartum hysterectomy, which is often associated with multiple surgical complications, severe maternal morbidity and mortality. The increased rates of cesarean sections lead to increased rates of scar pregnancies, which can have lethal consequences. Cesarean delivery has a negative impact on the infant immune system. This effect on the infant led to the introduction of a new concept called "Vaginal seeding". This refers to the practice of transferring some maternal vaginal fluid to the infant born via cesarean section in an effort to enhance its immune system.

Respiratory fluid mechanics

NASA Astrophysics Data System (ADS)

Grotberg, James B.

2011-02-01

This article covers several aspects of respiratory fluid mechanics that have been actively investigated by our group over the years. For the most part, the topics involve two-phase flows in the respiratory system with applications to normal and diseased lungs, as well as therapeutic interventions. Specifically, the topics include liquid plug flow in airways and at airway bifurcations as it relates to surfactant, drug, gene, or stem cell delivery into the lung; liquid plug rupture and its damaging effects on underlying airway epithelial cells as well as a source of crackling sounds in the lung; airway closure from "capillary-elastic instabilities," as well as nonlinear stabilization from oscillatory core flow which we call the "oscillating butter knife;" liquid film, and surfactant dynamics in an oscillating alveolus and the steady streaming, and surfactant spreading on thin viscous films including our discovery of the Grotberg-Borgas-Gaver shock.

Thermoelectricity in Heterogeneous Nanofluidic Channels.

PubMed

Li, Long; Wang, Qinggong

2018-05-01

Ionic fluids are essential to energy conversion, water desalination, drug delivery, and lab-on-a-chip devices. Ionic transport in nanoscale confinements and complex physical fields still remain elusive. Here, a nanofluidic system is developed using nanochannels of heterogeneous surface properties to investigate transport properties of ions under different temperatures. Steady ionic currents are observed under symmetric temperature gradients, which is equivalent to generating electricity using waste heat (e.g., electronic chips and solar panels). The currents increase linearly with temperature gradient and nonlinearly with channel size. Contributions to ion motion from temperatures and channel properties are evaluated for this phenomenon. The findings provide insights into the study of confined ionic fluids in multiphysical fields, and suggest applications in thermal energy conversion, temperature sensors, and chip-level thermal management. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Contactless and non-invasive delivery of micro-particles lying on a non-customized rigid surface by using acoustic radiation force.

PubMed

Meng, Jianxin; Mei, Deqing; Jia, Kun; Fan, Zongwei; Yang, Keji

2014-07-01

In the existing acoustic micro-particle delivery methods, the micro-particles always lie and slide on the surface of platform in the whole delivery process. To avoid the damage and contamination of micro-particles caused by the sliding motion, this paper deals with a novel approach to trap micro-particles from non-customized rigid surfaces and freely manipulate them. The delivery process contains three procedures: detaching, transporting, and landing. Hence, the micro-particles no longer lie on the surface, but are levitated in the fluid, during the long range transporting procedure. It is very meaningful especially for the fragile and easily contaminated targets. To quantitatively analyze the delivery process, a theoretical model to calculate the acoustic radiation force exerting upon a micro-particle near the boundary in half space is built. An experimental device is also developed to validate the delivery method. A 100 μm diameter micro-silica bead adopted as the delivery target is detached from the upper surface of an aluminum platform and levitated in the fluid. Then, it is transported along the designated path with high precision in horizontal plane. The maximum deviation is only about 3.3 μm. During the horizontal transportation, the levitation of the micro-silica bead is stable, the maximum fluctuation is less than 1 μm. The proposed method may extend the application of acoustic radiation force and provide a promising tool for microstructure or cell manipulation. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhalational system for Etoposide liposomes: formulation development and in vitro deposition.

PubMed

Parmar, J J; Singh, D J; Lohade, A A; Hegde, Darshana D; Soni, P S; Samad, A; Menon, Mala D

2011-11-01

Etoposide is a semisynthetic compound, widely used in treatment of non small cell lung cancer. However, frequent dosing and adverse effects remain a major concern in the use of etoposide. Liposomal systems for pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of etoposide was prepared by film hydration method. Various parameters were optimized with respect to entrapment efficiency as well as particle size of etoposide liposomes. For better shelf life of etoposide liposomes, freeze drying using trehalose as cryoprotectant was carried out. The liposomes were characterized for entrapment efficiency, particle size, surface topography, and in vitro drug release was carried out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±4°). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes.

Stereotactic CO2 laser therapy for hydrocephalus

NASA Astrophysics Data System (ADS)

Kozodoy-Pins, Rebecca L.; Harrington, James A.; Zazanis, George A.; Nosko, Michael G.; Lehman, Richard M.

1994-05-01

A new fiber-optic delivery system for CO2 radiation has been used to successfully treat non-communicating hydrocephalus. This system consists of a hollow sapphire waveguide employed in the lumen of a stereotactically-guided neuroendoscope. CO2 gas flows through the bore of the hollow waveguide, creating a path for the laser beam through the cerebrospinal fluid (CSF). This delivery system has the advantages of both visualization and guided CO2 laser radiation without the same 4.3 mm diameter scope. Several patients with hydrocephalus were treated with this new system. The laser was used to create a passage in the floor of the ventricle to allow the flow of CSF from the ventricles to the sub-arachnoid space. Initial postoperative results demonstrated a relief of the clinical symptoms. Long-term results will indicate if this type of therapy will be superior to the use of implanted silicone shunts. Since CO2 laser radiation at 10.6 micrometers is strongly absorbed by the water in tissue and CSF, damage to tissue surrounding the lesion with each laser pulse is limited. The accuracy and safety of this technique may prove it to be an advantageous therapy for obstructive hydrocephalus.

Azo polymeric micelles designed for colon-targeted dimethyl fumarate delivery for colon cancer therapy.

PubMed

Ma, Zhen-Gang; Ma, Rui; Xiao, Xiao-Lin; Zhang, Yong-Hui; Zhang, Xin-Zi; Hu, Nan; Gao, Jin-Lai; Zheng, Yu-Feng; Dong, De-Li; Sun, Zhi-Jie

2016-10-15

Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our previous work found that dimethyl fumarate (DMF), the approved drug by the FDA for the treatment of multiple sclerosis, exhibited anti-tumor activity on colon cancer cells. Based on the pharmacological properties of DMF and azo bond in olsalazine chemical structure, we designed azo polymeric micelles for colon-targeted dimethyl fumarate delivery for colon cancer therapy. We synthesized the star-shape amphiphilic polymer with azo bond and fabricated the DMF-loaded azo polymeric micelles. The four-arm polymer star-PCL-azo-mPEG (sPCEG-azo) (constituted by star-shape PCL (polycaprolactone) and mPEG (methoxypolyethylene glycols)-olsalazine) showed self-assembly ability. The average diameter and polydispersity index of the DMF-loaded sPCEG-azo polymeric micelles were 153.6nm and 0.195, respectively. In vitro drug release study showed that the cumulative release of DMF from the DMF-loaded sPCEG-azo polymeric micelles was no more than 20% in rat gastric fluid within 10h, whereas in the rat colonic fluids, the cumulative release of DMF reached 60% in the initial 2h and 100% within 10h, indicating that the DMF-loaded sPCEG-azo polymeric micelles had excellent colon-targeted property. The DMF-loaded sPCEG-azo polymeric micelles had no significant cytotoxicity on colon cancer cells in phosphate buffered solution (PBS) and rat gastric fluid. In rat colonic fluid, the micelles showed significant cytotoxic effect on colon cancer cells. The blank sPCEG-azo polymeric micelles (without DMF) showed no cytotoxic effect on colon cancer cells in rat colonic fluids. In conclusion, the DMF-loaded sPCEG-azo polymeric micelles show colon-targeted DMF release and anti-tumor activity, providing a novel approach potential for colon cancer therapy. Colon-targeted drug delivery and circumventing drug resistance are extremely important for colon cancer chemotherapy. Our previous work found that dimethyl fumarate (DMF), the approved drug by the FDA for the treatment of multiple sclerosis, exhibited anti-tumor activities on colon cancer cells (Br J Pharmacol. 2015 172(15):3929-43.). Based on the pharmacological properties of DMF and azo bond in olsalazine chemical structure, we designed azo polymeric micelles for colon-targeted dimethyl fumarate delivery for colon cancer therapy. We found that the DMF-loaded sPCEG-azo polymeric micelles showed colon-targeted DMF release and anti-tumor activities, providing a novel approach potential for colon cancer therapy. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Computational fluid dynamics (CFD) studies of a miniaturized dissolution system.

PubMed

Frenning, G; Ahnfelt, E; Sjögren, E; Lennernäs, H

2017-04-15

Dissolution testing is an important tool that has applications ranging from fundamental studies of drug-release mechanisms to quality control of the final product. The rate of release of the drug from the delivery system is known to be affected by hydrodynamics. In this study we used computational fluid dynamics to simulate and investigate the hydrodynamics in a novel miniaturized dissolution method for parenteral formulations. The dissolution method is based on a rotating disc system and uses a rotating sample reservoir which is separated from the remaining dissolution medium by a nylon screen. Sample reservoirs of two sizes were investigated (SR6 and SR8) and the hydrodynamic studies were performed at rotation rates of 100, 200 and 400rpm. The overall fluid flow was similar for all investigated cases, with a lateral upward spiraling motion and central downward motion in the form of a vortex to and through the screen. The simulations indicated that the exchange of dissolution medium between the sample reservoir and the remaining release medium was rapid for typical screens, for which almost complete mixing would be expected to occur within less than one minute at 400rpm. The local hydrodynamic conditions in the sample reservoirs depended on their size; SR8 appeared to be relatively more affected than SR6 by the resistance to liquid flow resulting from the screen. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing a commercially available sports drink on exogenous carbohydrate oxidation, fluid delivery and sustained exercise performance

PubMed Central

2014-01-01

Background Whilst exogenous carbohydrate oxidation (CHOEXO) is influenced by mono- and disaccharide combinations, debate exists whether such beverages enhance fluid delivery and exercise performance. Therefore, this study aimed to ascertain CHOEXO, fluid delivery and performance times of a commercially available maltodextrin/ fructose beverage in comparison to an isocaloric maltodextrin beverage and placebo. Methods Fourteen club level cyclists (age: 31.79 ± 10.02 years; height: 1.79 ± 0.06 m; weight: 73.69 ± 9.24 kg; VO2max: 60.38 ± 9.36 mL · kg·-1 min-1) performed three trials involving 2.5 hours continuous exercise at 50% maximum power output (Wmax: 176.71 ± 25.92 W) followed by a 60 km cycling performance test. Throughout each trial, athletes were randomly assigned, in a double-blind manner, either: (1) 1.1 g · min-1 maltodextrin + 0.6 g · min-1 fructose (MD + F), (2) 1.7 g · min-1 of maltodextrin (MD) or (3) flavoured water (P). In addition, the test beverage at 60 minutes contained 5.0 g of deuterium oxide (2H2O) to assess quantification of fluid delivery. Expired air samples were analysed for CHOEXO according to the 13C/12C ratio method using gas chromatography continuous flow isotope ratio mass spectrometry. Results Peak CHOEXO was significantly greater in the final 30 minutes of submaximal exercise with MD + F and MD compared to P (1.45 ± 0.09 g · min-1, 1.07 ± 0.03 g · min-1and 0.00 ± 0.01 g · min-1 respectively, P < 0.0001), and significantly greater for MD + F compared to MD (P = 0.005). The overall appearance of 2H2O in plasma was significantly greater in both P and MD + F compared to MD (100.27 ± 3.57 ppm, 92.57 ± 2.94 ppm and 78.18 ± 4.07 ppm respectively, P < 0.003). There was no significant difference in fluid delivery between P and MD + F (P = 0.078). Performance times significantly improved with MD + F compared with both MD (by 7 min 22 s ± 1 min 56 s, or 7.2%) and P (by 6 min 35 s ± 2 min 33 s, or 6.5%, P < 0.05) over 60 km. Conclusions A commercially available maltodextrin-fructose beverage improves CHOEXO and fluid delivery, which may benefit individuals during sustained moderate intensity exercise. The greater CHOEXO observed when consuming a maltodextrin-fructose beverage may support improved performance times. PMID:24589205

Insights of Mixing on the Assembly of DNA Nanoparticles

NASA Astrophysics Data System (ADS)

Williams, Manda S.

Size is a crucial parameter in the delivery of nanoparticle therapeutics, affecting mechanisms such as tissue delivery, clearance, and cellular uptake. The morphology of nanoparticles is dependent both upon chemistry and the physical process of assembly. Polyplexes, a major class of non-viral gene delivery vectors, are conventionally prepared by vortex mixing, resulting in non-uniform nanoparticles and poor reproducibility. Better understanding and control of the physical process of assembly, and mixing in particular, will produce polyplexes of a more uniform and reliable size, optimizing their efficiency for laboratory and clinical use. "Mixing" is the reduction of length scale of a system to accelerate diffusion until a uniform concentration is achieved. Vortex mixing is poorly characterized and sensitive to protocols. Microfluidic systems are notable for predictable fluid behavior, and are ideal for analyzing and controlling the physical interaction of reagents on the microscale, realm where mixing occurs. Several microdevices for the preparation of DNA polyplexes are explored here. Firstly, the staggered herringbone mixer, a chaotic advection micromixer, is used to observe the effects of mixing time on nanoparticle size. Next, a novel device to surround the reagent flows with a sheath of buffer, preventing interaction with the walls and confining the complexation to a zone of lower, less variable shear and residence time, is used to demonstrate the role of shear in nanoparticle assembly. Lastly, uneven diffusion between ion pairs produces a small separation of charge at fluid interfaces; this short-lived electric field has a significant impact on the transport of DNA over the time scales of mixing and complexation. The effects of common buffers on the transport of DNA are examined for possible applications to mixing and complexation. These three investigations demonstrate the importance of the physical process in polyplex assembly, and indicate several important considerations in the development of new protocols and devices.

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

Mechanism of enhanced oral absorption of morin by phospholipid complex based self-nanoemulsifying drug delivery system.

PubMed

Zhang, Jinjie; Li, Jianbo; Ju, Yuan; Fu, Yao; Gong, Tao; Zhang, Zhirong

2015-02-02

Phospholipid complex (PLC) based self-nanoemulsifying drug delivery system (PLC-SNEDDS) has been developed for efficient delivery of drugs with poor solubility and low permeability. In the present study, a BCS class IV drug and a P-glycoprotein (P-gp) substrate, morin, was selected as the model drug to elucidate the oral absorption mechanism of PLC-SNEDDS. PLC-SNEDDS was superior to PLC in protecting morin from degradation by intestinal enzymes in vitro. In situ perfusion study showed increased intestinal permeability by PLC was duodenum-specific. In contrast, PLC-SNEDDS increased morin permeability in all intestinal segments and induced a change in the main absorption site of morin from colon to ileum. Moreover, ileum conducted the lymphatic transport of PLC-SNEDDS, which was proven by microscopic intestinal visualization of Nile red labeled PLC-SNEDDS and lymph fluids in vivo. Low cytotoxicity and increased Caco-2 cell uptake suggested a safe and efficient delivery of PLC-SNEDDS. The increased membrane fluidity and disrupted actin filaments were closely associated with the increased cell uptake of PLC-SNEDDS. PLC-SNEDDS could be internalized into enterocytes as an intact form in a cholesterol-dependent manner via clathrin-mediated endocytosis and macropinocytosis. The enhanced oral absorption of morin was attributed to the P-gp inhibition by Cremophor RH and the intact internalization of M-PLC-SNEDDS into Caco-2 cells bypassing P-gp recognition. Our findings thus provide new insights into the development of novel nanoemulsions for poorly absorbed drugs.

Biomaterials and Magnetic fields for Cancer Therapy

NASA Technical Reports Server (NTRS)

Ramachandran, Narayanan; Mazuruk, Konstanty

2003-01-01

The field of biomaterials has emerged as an important topic in the purview of NASA s new vision of research activities in the Microgravity Research Division. Although this area has an extensive track record in the medical field as borne out by the routine use of polymeric sutures, implant devices, and prosthetics, novel applications such as tissue engineering, artificial heart valves and controlled drug delivery are beginning to be developed. Besides the medical field, biomaterials and bio-inspired technologies are finding use in a host of emerging interdisciplinary fields such as self-healing and self-assembling structures, biosensors, fuel systems etc. The field of magnetic fluid technology has several potential applications in medicine. One of the emerging fields is the area of controlled drug delivery, which has seen its evolution from the basic oral delivery system to pulmonary to transdermal to direct inoculations. In cancer treatment by chemotherapy for example, targeted and controlled drug delivery has received vast scrutiny and substantial research and development effort, due to the high potency of the drugs involved and the resulting requirement to keep the exposure of the drugs to surrounding healthy tissue to a minimum. The use of magnetic particles in conjunction with a static magnetic field allows smart targeting and retention of the particles at a desired site within the body with the material transport provided by blood perfusion. Once so located, the therapeutical aspect (radiation, chemotherapy, hyperthermia, etc.) of the treatment, now highly localized, can be implemented.

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.

EPR: Evidence and fallacy.

PubMed

Nichols, Joseph W; Bae, You Han

2014-09-28

The enhanced permeability and retention (EPR) of nanoparticles in tumors has long stood as one of the fundamental principles of cancer drug delivery, holding the promise of safe, simple and effective therapy. By allowing particles preferential access to tumors by virtue of size and longevity in circulation, EPR provided a neat rationale for the trend toward nano-sized drug carriers. Following the discovery of the phenomenon by Maeda in the mid-1980s, this rationale appeared to be well justified by the flood of evidence from preclinical studies and by the clinical success of Doxil. Clinical outcomes from nano-sized drug delivery systems, however, have indicated that EPR is not as reliable as previously thought. Drug carriers generally fail to provide superior efficacy to free drug systems when tested in clinical trials. A closer look reveals that EPR-dependent drug delivery is complicated by high tumor interstitial fluid pressure (IFP), irregular vascular distribution, and poor blood flow inside tumors. Furthermore, the animal tumor models used to study EPR differ from clinical tumors in several key aspects that seem to make EPR more pronounced than in human patients. On the basis of this evidence, we believe that EPR should only be invoked on a case-by-case basis, when clinical evidence suggests the tumor type is susceptible. Copyright © 2014 Elsevier B.V. All rights reserved.

Buoyancy-generating agents for stomach-specific drug delivery: an overview with special emphasis on floating behavior.

PubMed

Ishak, Rania A H

2015-01-01

Gastric retentive drug delivery provides a promising technology exhibiting an extended gastric residence and a drug release independent of patient related variables. It is usually useful in improving local gastric treatment as well as overcoming drug-related problems .i.e. drugs having narrow absorption window, short half-life or low intestinal solubility. Buoyancy is considered one of the most promising approaches for gastro-retention of dosage forms. Floating drug delivery systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach causing an increase in gastric residence time. The buoyancy of these systems is attained by the aid of substances responsible to generate the low density. Various agents with different mechanisms were adopted either gas-generating agents, air entrapping swellable polymers, inherent low density substances, porous excipients, hollow/porous particles inducing preparation techniques or sublimating agents. Therefore, this review gives an exclusive descriptive classification of the different categories of these buoyancy-generating agents while representing the related research works. An overview is also conducted to describe relevant techniques assessing the floating behavior of such dosage forms either in vitro or in vivo. Finally, a collection representing FDA-approved floating pharmaceutical products is adopted with emphasis on the buoyancy-generating agent type used in each product.

Amnioinfusion in labor induction of term pregnancies with premature rupture of the membranes and low amniotic fluid.

PubMed

Miño, M; Puertas, A; Herruzo, A J; Miranda, J A

1998-05-01

To analyze the utility of prophylactic amnioinfusion in term pregnancies with PROM and a low amniotic fluid index during labor induction. Forty-two women with amnioinfusion and 42 in a control group with amniotic fluid index (AFI) below 10 cm when admitted to labor induction were studied. All patients had electronic fetal heart rate and intrauterine pressure continuous monitoring. Amnioinfusion of normal saline (37 degrees C) was realized in the study group, using a continuous perfusion pump at 600 ml/h for 1 h, after which the AFI was again recorded; if this was < 15, the perfusion was continued at 180 ml/h until full cervical dilatation was achieved or until uterine baseline activity reached 20 mm Hg. The control group received identical obstetric care except in respect of amnioinfusion. Both groups were similar in age, primiparity, gestational age, initial AFI, interval from rupture of membranes until delivery and length of labor. The amnioinfusion of 600 ml in 1 h significantly increased the AFI (an increase of 7.2 +/- 3.9 vs. a decrease of 1.1 +/- 1.6, P < 0.01). In the amnioinfusion group, there was a significantly lower rate of cesarean deliveries (0 vs. 6, P < 0.05) and a better mean umbilical arterial pH at delivery (7.24 +/- 0.07 vs. 7.21 +/- 0.08, P < 0.05). No differences were observed in maternal or neonatal hospitalization days or infectious morbidity. It is concluded that prophylactic amnioinfusion improves neonatal metabolic state when used in labor induction of term pregnancies with PROM and a low amniotic fluid index.

Characterization and evaluation in vivo of baicalin-nanocrystals prepared by an ultrasonic-homogenization-fluid bed drying method.

PubMed

Shi-Ying, Jin; Jin, Han; Shi-Xiao, Jin; Qing-Yuan, Lv; Jin-Xia, Bai; Chen, Hong-Ge; Rui-Sheng, Li; Wei, Wu; Hai-Long, Yuan

2014-01-01

To improve the absorption and bioavailability of baicalin using a nanocrystal (or nanosuspension) drug delivery system. A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo. The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of -34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 μg·mL(-1), was much higher than the baicalin-microcrystals and the physical mixture (135 and 86.4 μg·mL(-1), respectively). In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability (with the AUC(0-t) value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L(-1)·h(-1), respectively). The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure baicalin coarse powder and micronized baicalin. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Optimal Control of Objects on the Micro- and Nano-Scale by Electrokinetic and Electromagnetic Manipulation: for Bio-Sample Preparation, Quantum Information Devices and Magnetic Drug Delivery

DTIC Science & Technology

2010-01-01

property variations. The system described here is a simple 4-electrode microfluidic device made of polydimethylsiloxane PDMS [50-53] which is reversibly...through the fluid and heat it.) A more detailed description and analysis of the physics of electroosmotic actuation can be found in [46, 83] In...a control algorithm on a standard personal computer. The micro-fluidic device is made out of a soft polymer ( polydimethylsiloxane (PDMS)) and is

In utero negativization of Zika virus in a foetus with serious central nervous system abnormalities.

PubMed

Rodó, C; Suy, A; Sulleiro, E; Soriano-Arandes, A; Antón, A; García-Ruiz, I; Arévalo, S; Vázquez, É; Vázquez, A; de Ory, F; Sánchez-Seco, M P; Rodrigo, C; Pumarola, T; Carreras, E

2018-05-01

We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract). Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Nonviral siRNA delivery for gene silencing in neurodegenerative diseases.

PubMed

Prakash, Satya; Malhotra, Meenakshi; Rengaswamy, Venkatesh

2010-01-01

Linking genes with the underlying mechanisms of diseases is one of the biggest challenges of genomics-driven drug discovery research. Designing an inhibitor for any neurodegenerative disease that effectively halts the pathogenicity of the disease is yet to be achieved. The challenge lies in crossing the blood-brain barrier (BBB)/blood-cerebrospinal fluid barrier (BCSFB) to reach the catalytic pockets of the enzyme/protein involved in the molecular mechanism of the disease process. Designing siRNA with exquisite specificity may result in selective suppression of the disease-linked gene. Although siRNA is the most promising method, it loses its potency in downregulating the gene due to its inherent instability, off-target effects, and lack of on-target effective delivery systems. Viral as well as nonviral delivery methods have been effectively tested in vivo for silencing of molecular targets and have resulted in significant efficacy in animal models of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), anxiety, depression, encephalitis, glioblastoma, Huntington's disease, neuropathic pain, and spinocerebellar ataxia. To realize the full therapeutic potential of siRNA for neurodegenerative diseases, we need to overcome many hurdles and challenges such as selecting suitable tissue-specific delivery vectors, minimizing the off-target effects, and achieving distribution in sufficient concentrations at the target tissue without any side effects. Cationic nanoparticle-mediated targeted siRNA delivery for therapeutic purposes has gained considerable clinical importance as a result of its promising efficacy.

Hydroxypropyl-β-cyclodextrin for Delivery of Baicalin via Inclusion Complexation by Supercritical Fluid Encapsulation.

PubMed

Li, Ying; He, Zhen-Dan; Zheng, Qian-En; Hu, Chengshen; Lai, Wing-Fu

2018-05-14

Over the years, various methods have been developed to enhance the solubility of insoluble drugs; however, most of these methods are time-consuming and labor intensive or involve the use of toxic materials. A method that can safely and effectively enhance the solubility of insoluble drugs is lacking. This study adopted baicalin as an insoluble drug model, and used hydroxypropyl-β-cyclodextrin for the delivery of baicalin via the inclusion complexation by supercritical fluid encapsulation. Different parameters for the complex preparation as well as the physicochemical properties of the complex have been investigated. Our results showed that when compared to the conventional solution mixing approach, supercritical fluid encapsulation enables a more precise control of the properties of the complex, and gives higher loading and encapsulation efficiency. It is anticipated that our reported method can be useful in enhancing the preparation efficiency of inclusion complexes, and can expand the application potential of insoluble herbal ingredients in treatment development and pharmaceutical formulation.

Enhancement of non-invasive trans-membrane drug delivery using ultrasound and microbubbles during physiologically relevant flow.

PubMed

Shamout, Farah E; Pouliopoulos, Antonios N; Lee, Patrizia; Bonaccorsi, Simone; Towhidi, Leila; Krams, Rob; Choi, James J

2015-09-01

Sonoporation has been associated with drug delivery across cell membranes and into target cells, yet several limitations have prohibited further advancement of this technology. Higher delivery rates were associated with increased cellular death, thus implying a safety-efficacy trade-off. Meanwhile, there has been no reported study of safe in vitro sonoporation in a physiologically relevant flow environment. The objective of our study was not only to evaluate sonoporation under physiologically relevant flow conditions, such as fluid velocity, shear stress and temperature, but also to design ultrasound parameters that exploit the presence of flow to maximize sonoporation efficacy while minimizing or avoiding cellular damage. Human umbilical vein endothelial cells (EA.hy926) were seeded in flow chambers as a monolayer to mimic the endothelium. A peristaltic pump maintained a constant fluid velocity of 12.5 cm/s. A focused 0.5 MHz transducer was used to sonicate the cells, while an inserted focused 7.5 MHz passive cavitation detector monitored microbubble-seeded cavitation emissions. Under these conditions, propidium iodide, which is normally impermeable to the cell membrane, was traced to determine whether it could enter cells after sonication. Meanwhile, calcein-AM was used as a cell viability marker. A range of focused ultrasound parameters was explored, with several unique bioeffects observed: cell detachment, preservation of cell viability with no membrane penetration, cell death and preservation of cell viability with sonoporation. The parameters were then modified further to produce safe sonoporation with minimal cell death. To increase the number of favourable cavitation events, we lowered the ultrasound exposure pressure to 40 kPapk-neg and increased the number of cavitation nuclei by 50 times to produce a trans-membrane delivery rate of 62.6% ± 4.3% with a cell viability of 95% ± 4.2%. Furthermore, acoustic cavitation analysis showed that the low pressure sonication produced stable and non-inertial cavitation throughout the pulse sequence. To our knowledge, this is the first study to demonstrate a high drug delivery rate coupled with high cell viability in a physiologically relevant in vitro flow system. Copyright © 2015. Published by Elsevier Inc.

Magnetic timing valves for fluid control in paper-based microfluidics.

PubMed

Li, Xiao; Zwanenburg, Philip; Liu, Xinyu

2013-07-07

Multi-step analytical tests, such as an enzyme-linked immunosorbent assay (ELISA), require delivery of multiple fluids into a reaction zone and counting the incubation time at different steps. This paper presents a new type of paper-based magnetic valves that can count the time and turn on or off a fluidic flow accordingly, enabling timed fluid control in paper-based microfluidics. The timing capability of these valves is realized using a paper timing channel with an ionic resistor, which can detect the event of a solution flowing through the resistor and trigger an electromagnet (through a simple circuit) to open or close a paper cantilever valve. Based on this principle, we developed normally-open and normally-closed valves with a timing period up to 30.3 ± 2.1 min (sufficient for an ELISA on paper-based platforms). Using the normally-open valve, we performed an enzyme-based colorimetric reaction commonly used for signal readout of ELISAs, which requires a timed delivery of an enzyme substrate to a reaction zone. This design adds a new fluid-control component to the tool set for developing paper-based microfluidic devices, and has the potential to improve the user-friendliness of these devices.

Using 'nudge' principles for order set design: a before and after evaluation of an electronic prescribing template in critical care.

PubMed

Bourdeaux, Christopher P; Davies, Keith J; Thomas, Matthew J C; Bewley, Jeremy S; Gould, Timothy H

2014-05-01

Computerised order sets have the potential to reduce clinical variation and improve patient safety but the effect is variable. We sought to evaluate the impact of changes to the design of an order set on the delivery of chlorhexidine mouthwash and hydroxyethyl starch (HES) to patients in the intensive care unit. The study was conducted at University Hospitals Bristol NHS Foundation Trust, UK. Our intensive care unit uses a clinical information system (CIS). All drugs and fluids are prescribed with the CIS and drug and fluid charts are stored within a database. Chlorhexidine mouthwash was added as a default prescription to the prescribing template in January 2010. HES was removed from the prescribing template in April 2009. Both interventions were available to prescribe manually throughout the study period. We conducted a database review of all patients eligible for each intervention before and after changes to the configuration of choices within the prescribing system. 2231 ventilated patients were identified as appropriate for treatment with chlorhexidine, 591 before the intervention and 1640 after. 55.3% were prescribed chlorhexidine before the change and 90.4% after (p<0.001). 6199 patients were considered in the HES intervention, 2177 before the intervention and 4022 after. The mean volume of HES infused per patient fell from 630 mL to 20 mL after the change (p<0.001) and the percentage of patients receiving HES fell from 54.1% to 3.1% (p<0.001). These results were well sustained with time. The presentation of choices within an electronic prescribing system influenced the delivery of evidence-based interventions in a predictable way and the effect was well sustained. This approach has the potential to enhance the effectiveness of computerised order sets.

Preliminary study on carprofen concentration measurements after transcutaneous treatment with Vetdrop® in a microfracture joint defect model in sheep.

PubMed

Sidler, Michèle; Fouché, Nathalie; Meth, Ingmar; von Hahn, Friedrich; von Rechenberg, Brigitte; Kronen, Peter W

2014-12-09

The present preliminary study describes concentration time courses of the NSAID carprofen in the plasma and synovial fluid in a microfrature sheep model after transcutaneous treatments with a novel application device (Vetdrop®). To treat circumscribed inflammatory processes a transcutaneous application device could potentially be beneficial. After transcutaneous application normally lower systemic concentrations are measured which may reduce the incidence of side effects, whereas efficacy is still maintained. In this study carprofen was used based on its capacity to provide analgesia after orthopaedic procedures in sheep and it is considered that it may have a positive influence on the healing of cartilage in low concentrations. In all transcutaneously treated animals, carprofen plasma concentrations exceeded those of synovial fluid, although plasma levels remained significantly reduced (300-fold) as compared to carprofen administered intravenously. Furthermore, in contrast to the intravenously treated animals, a modest accumulation of carprofen in plasma and synovial fluid was observed in the transcutaneously treated animals over the 6-week treatment period. The transcutaneously administered carprofen using the Vetdrop® device penetrated the skin and both, plasma- and synovial concentrations could be measured repeatedly over time. This novel device may be considered a valuable transcutaneous drug delivery system.

Challenges of a negative work load and implications on morale, productivity and quality of service delivered in NHS laboratories in England

PubMed Central

Osaro, Erhabor; Chima, Njemanze

2014-01-01

The National Health Service (NHS) is a term used to describe the publicly funded healthcare delivery system providing quality healthcare services in the United Kingdom. There are several challenges militating against the effective laboratory service delivery in the NHS in England. Biomedical scientists work in healthcare to diagnose disease and evaluate the effectiveness of treatment through the analysis of body fluids and tissue samples from patients. They provide the “engine room” of modern medicine with 70% of diagnosis based on the laboratory results generated by them. This review involved the search of literature for information on working condition of biomedical scientist in the NHS in England. Laboratory service delivery in the NHS in England faces numerous daunting challenges; staffing levels in the last few years have become dangerously low, less remunerated, relatively less experienced and predominantly band 5's, multidisciplinary rather than specialty based, associated with working more unsocial hours without adequate recovery time, de-banding of staff, high staff turnaround, profit and cost driven rather than quality. These factors has resulted in burn out, low morale, high sickness absences, increased error rate, poor team spirit, diminished productivity and suboptimal laboratory service delivery. There is the urgent need to retract our steps on unpopular policies to ensure that patient care is not compromised by ensuring adequate staffing level and mix, ensuring adequate remuneration of laboratory staff, implementing evidenced-based specialty oriented service, determining the root cause/s for the high staff turnover and implementing corrective action, identifying other potential sources of waste in the system rather than pruning the already dangerously low staffing levels and promoting a quality delivery side by side cost effectiveness. PMID:25182941

In vitro and in vivo evaluation of a water-in-oil microemulsion system for enhanced peptide intestinal delivery.

PubMed

Liu, Dongyun; Kobayashi, Taku; Russo, Steven; Li, Fengling; Plevy, Scott E; Gambling, Todd M; Carson, Johnny L; Mumper, Russell J

2013-01-01

Peptide and protein drugs have become the new generation of therapeutics, yet most of them are only available as injections, and reports on oral local intestinal delivery of peptides and proteins are quite limited. The aim of this work was to develop and evaluate a water-in-oil (w/o) microemulsion system in vitro and in vivo for local intestinal delivery of water-soluble peptides after oral administration. A fluorescent labeled peptide, 5-(and-6)-carboxytetramethylrhodamine labeled HIV transactivator protein TAT (TAMRA-TAT), was used as a model peptide. Water-in-oil microemulsions consisting of Miglyol 812, Capmul MCM, Tween 80, and water were developed and characterized in terms of appearance, viscosity, conductivity, morphology, and particle size analysis. TAMRA-TAT was loaded and its enzymatic stability was assessed in modified simulated intestinal fluid (MSIF) in vitro. In in vivo studies, TAMRA-TAT intestinal distribution was evaluated using fluorescence microscopy after TAMRA-TAT microemulsion, TAMRA-TAT solution, and placebo microemulsion were orally gavaged to mice. The half-life of TAMRA-TAT in microemulsion was enhanced nearly three-fold compared to that in the water solution when challenged by MSIF. The treatment with TAMRA-TAT microemulsion after oral administration resulted in greater fluorescence intensity in all intestine sections (duodenum, jejunum, ileum, and colon) compared to TAMRA-TAT solution or placebo microemulsion. The in vitro and in vivo studies together suggested TAMRA-TAT was better protected in the w/o microemulsion in an enzyme-containing environment, suggesting that the w/o microemulsions developed in this study may serve as a potential delivery vehicle for local intestinal delivery of peptides or proteins after oral administration.

Challenges of a negative work load and implications on morale, productivity and quality of service delivered in NHS laboratories in England.

PubMed

Osaro, Erhabor; Chima, Njemanze

2014-06-01

The National Health Service (NHS) is a term used to describe the publicly funded healthcare delivery system providing quality healthcare services in the United Kingdom. There are several challenges militating against the effective laboratory service delivery in the NHS in England. Biomedical scientists work in healthcare to diagnose disease and evaluate the effectiveness of treatment through the analysis of body fluids and tissue samples from patients. They provide the "engine room" of modern medicine with 70% of diagnosis based on the laboratory results generated by them. This review involved the search of literature for information on working condition of biomedical scientist in the NHS in England. Laboratory service delivery in the NHS in England faces numerous daunting challenges; staffing levels in the last few years have become dangerously low, less remunerated, relatively less experienced and predominantly band 5's, multidisciplinary rather than specialty based, associated with working more unsocial hours without adequate recovery time, de-banding of staff, high staff turnaround, profit and cost driven rather than quality. These factors has resulted in burn out, low morale, high sickness absences, increased error rate, poor team spirit, diminished productivity and suboptimal laboratory service delivery. There is the urgent need to retract our steps on unpopular policies to ensure that patient care is not compromised by ensuring adequate staffing level and mix, ensuring adequate remuneration of laboratory staff, implementing evidenced-based specialty oriented service, determining the root cause/s for the high staff turnover and implementing corrective action, identifying other potential sources of waste in the system rather than pruning the already dangerously low staffing levels and promoting a quality delivery side by side cost effectiveness.

Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model

PubMed Central

Welter, Michael; Rieger, Heiko

2013-01-01

Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider–with the help of a theoretical model–the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells. PMID:23940570

New developments in the treatment of type 1 diabetes mellitus.

PubMed

Haak, T

1999-01-01

Treatment of type 1 diabetes mellitus has made tremendous advances within the last decades. With concern to insulin delivery there are two promising new approaches. One is the intrapulmonary insulin delivery which has become feasible by the development of new inhalation devices which provide a sufficient degree of intrapulmonary drug retention. Also oral insulin delivery seems feasible when surface active substances are used to cross the mucosal membrane in the gut. Clinical research has also focussed on coatings for the insulin molecules to solve the problem raised by the proteolytic activity of the digestive system. A very new agent produced by a fungus called Pseudomassaria has been demonstrated to reverse the clinical signs of diabetes mellitus in mice. The compound diffuses through the cell membrane, binds to the inner part of the insulin receptor and activates the insulin typical biological effects. Nowadays a variety of insulin analogs are designed and tested for their clinical use. By shifting the isoelectric point towards to a slightly acidic pH, HOE 901 precipitates at physiologic pH resulting in a constant and peakless insulin delivery. NN 304 is a 14-carbon aliphatic fatty acid acylated analog that binds to serum albumin resulting in a flatter time-action profile than NPH insulin. Also rapid acting insulin analogs are or will be launched in the near future aiming to ensure an improved postprandial glucose regulation. Glucagon-like peptide-1 (GLP-1) improves metabolic control by a variety of effects, e.g. the enhancement of insulin secretion and inhibition of glucagon secretion. Moreover, GLP-1 reduces food and water intake controlled by the brain, and inhibits gastric emptying. A disadvantage of GLP-1 is its very short half-life. Novel derivatives with the beneficial effects of GLP-1 but a better resistance against degradation have been designed. In addition substances have been developed inhibiting GLP-1 degradation or augmenting GLP-1 release from its abundant endogenous pool. Finally, there is a variety of interesting approaches aiming to improve or ease blood glucose self-monitoring. One is the development of subcutaneous catheters for continuous blood glucose control. In another system reverse iontophoresis is used for sampling interstitial fluid which reflects capillary blood glucose levels. Instead of using an electric current, a brandnew system creates micropores in the skin by a laser ablation system. Through these micropores a specific device performs a mild suction to obtain intersitial fluid. Further systems which measure blood glucose by near infrared spectroscopy are still investigated in order to improve their technical function and to reduce their weight. This article intends to give an overview over the new developments in the treatment and management of type-1-diabetes mellitus.

Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes.

PubMed

García, Mónica C; Martinelli, Marisa; Ponce, Nicolás E; Sanmarco, Liliana M; Aoki, María P; Manzo, Rubén H; Jimenez-Kairuz, Alvaro F

2018-07-30

Interpolyelectrolyte complexes (IPEC) formulated as multiparticulate drug delivery systems (MDDS) are interesting carriers to improve drug' performance. Benznidazole (BZ) is the first-line drug for Chagas treatment; however, it presents side effects and toxicity, conditioning its efficacy and safety. The goal of this work was to obtain novel MDDS composed by IPEC based on different polymethacrylate carriers loaded with BZ and to investigate in vitro drug delivery performance for oral administration. Physicochemical characterizations were studied and preclinical studies in a murine model of acute Chagas disease were also performed. The MDDS composed by BZ-loaded IPEC based on polymethacrylates were obtained by casting solvent followed by wet granulation methods with yields >83%. FT-IR demonstrated ionic interaction between the polyelectrolytes. Confocal microscopy, DSC and PXRD revealed a fraction uniformly distributed of free BZ on the multiparticles. The rheological evaluation of the MDDS showed adequate flow features for their formulation in hard gelatin-capsules. The type and composition of IPEC conditioned the modulation of BZ release and fluid uptake results. MDDS based on more hydrophylic Eudragit® showed very fast dissolution (Q 15min  > 85%), while an extended release (Q 120min  ≤ 40%) for the hydrophobic ones was observed. Capsules containing a combination of two MDDS with different release profile of BZ showed promising properties to improve Chagas disease pharmacotherapy in the preliminary in vivo assay performed, in which the BZ-loaded MDDS exhibited efficacy to reduce parasitemia, while decreasing the levels of liver injury markers in comparison to BZ conventional treatment. Multi-kinetic BZ delivery systems developed are interesting pharmaceutical alternatives to improve the treatment of Chagas disease. Copyright © 2018. Published by Elsevier B.V.

AAV viral vector delivery to the brain by shape-conforming MR-guided infusions.

PubMed

Bankiewicz, Krystof S; Sudhakar, Vivek; Samaranch, Lluis; San Sebastian, Waldy; Bringas, John; Forsayeth, John

2016-10-28

Gene transfer technology offers great promise as a potential therapeutic approach to the brain but has to be viewed as a very complex technology. Success of ongoing clinical gene therapy trials depends on many factors such as selection of the correct genetic and anatomical target in the brain. In addition, selection of the viral vector capable of transfer of therapeutic gene into target cells, along with long-term expression that avoids immunotoxicity has to be established. As with any drug development strategy, delivery of gene therapy has to be consistent and predictable in each study subject. Failed drug and vector delivery will lead to failed clinical trials. In this article, we describe our experience with AAV viral vector delivery system, that allows us to optimize and monitor in real time viral vector administration into affected regions of the brain. In addition to discussing MRI-guided technology for administration of AAV vectors we have developed and now employ in current clinical trials, we also describe ways in which infusion cannula design and stereotactic trajectory may be used to maximize the anatomical coverage by using fluid backflow. This innovative approach enables more precise coverage by fitting the shape of the infusion to the shape of the anatomical target. Copyright © 2016 Elsevier B.V. All rights reserved.

Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

PubMed

Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

Development and evaluation of inhalational liposomal system of budesonide for better management of asthma.

PubMed

Parmar, J J; Singh, D J; Hegde, Darshana D; Lohade, A A; Soni, P S; Samad, A; Menon, Mala D

2010-07-01

Budesonide is a corticosteroid used by inhalation in the prophylactic management of asthma. However, frequent dosing and adverse effects (local and systemic) remain a major concern in the use of budesonide. Liposomal systems for sustained pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of budesonide was prepared by film hydration method and evaluated for sustained release. Various parameters were optimized with respect to entrapment efficiency as well as particle size of budesonide liposomes. For better shelf life of budesonide liposomes, they were freeze dried using trehalose as cryoprotectant. The liposomes were characterized for entrapment efficiency, particle size, and surface topography; in vitro drug release was evaluated out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±40). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes.

Development and Evaluation of Inhalational Liposomal System of Budesonide for Better Management of Asthma

PubMed Central

Parmar, J. J.; Singh, D. J.; Hegde, Darshana D.; Lohade, A. A.; Soni, P. S.; Samad, A.; Menon, Mala D.

2010-01-01

Budesonide is a corticosteroid used by inhalation in the prophylactic management of asthma. However, frequent dosing and adverse effects (local and systemic) remain a major concern in the use of budesonide. Liposomal systems for sustained pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of budesonide was prepared by film hydration method and evaluated for sustained release. Various parameters were optimized with respect to entrapment efficiency as well as particle size of budesonide liposomes. For better shelf life of budesonide liposomes, they were freeze dried using trehalose as cryoprotectant. The liposomes were characterized for entrapment efficiency, particle size, and surface topography; in vitro drug release was evaluated out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±40). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes. PMID:21218054

Dynamically Stable Legged Locomotion

DTIC Science & Technology

1989-09-01

length during overground locomotion: task-specific modulation of the locomotor synergy. Journal of Experimental Psychology, 15(3). Raibert, M. I. 1986...energy conversions that intermediates between combus- tion of a fluid fuel such as gasoline , and the controlled delivery of force and power to the...question of this study: Can the extremely high energy density and rapid response of combustible fluid fuels such as gasoline be harnessed to produce

Respiratory fluid mechanics

PubMed Central

Grotberg, James B.

2011-01-01

This article covers several aspects of respiratory fluid mechanics that have been actively investigated by our group over the years. For the most part, the topics involve two-phase flows in the respiratory system with applications to normal and diseased lungs, as well as therapeutic interventions. Specifically, the topics include liquid plug flow in airways and at airway bifurcations as it relates to surfactant, drug, gene, or stem cell delivery into the lung; liquid plug rupture and its damaging effects on underlying airway epithelial cells as well as a source of crackling sounds in the lung; airway closure from “capillary-elastic instabilities,” as well as nonlinear stabilization from oscillatory core flow which we call the “oscillating butter knife;” liquid film, and surfactant dynamics in an oscillating alveolus and the steady streaming, and surfactant spreading on thin viscous films including our discovery of the Grotberg–Borgas–Gaver shock. PMID:21403768

Microfluidic Controlled Conformal Coating of Particles

NASA Astrophysics Data System (ADS)

Tsai, Scott; Wexler, Jason; Wan, Jiandi; Stone, Howard

2011-11-01

Coating flows are an important class of fluid mechanics problems. Typically a substrate is coated with a moving continuous film, but it is also possible to consider coating of discrete objects. In particular, in applications involving coating of particles that are useful in drug delivery, the coatings act as drug-carrying vehicles, while in cell therapy a thin polymeric coating is required to protect the cells from the host's immune system. Although many functional capabilities have been developed for lab-on-a-chip devices, a technique for coating has not been demonstrated. We present a microfluidic platform developed to coat micron-size spheres with a thin aqueous layer by magnetically pulling the particles from the aqueous phase to the non-aqueous phase in a co-flow. Coating thickness can be adjusted by the average fluid speed and the number of beads encapsulated inside a single coat is tuned by the ratio of magnetic to interfacial forces acting on the beads.

Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

PubMed

Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

2014-02-01

The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

Effects of membrane composition on release of model hydrophilic compound from osmotic delivery systems.

PubMed

Ozdemir, N; Ozalp, Y; Ozkan, Y

2000-01-01

In this study, the effects of surface-active agents in different types and concentrations, added into the coating solution, on release of model hydrophilic compound have been examined. For this purpose, the tablets, prepared with the use of methylene blue as a model substance, were coated by spray coating technique with cellulose acetate solution containing polyethylene glycol 400 as a plasticizer. In addition, cetylpyridinium chloride as cationic surface-active agent and sodium lauryl sulphate as anionic surface-active agent were added into coating solution in different concentrations. After creating a delivery orifice by a microdrill on the tablets, release of model hydrophilic compound was tested by the USP paddle method. The data obtained were evaluated according to the different kinetics and the mechanism of release from the preparations was examined. The surface properties of the coating material were investigated by scanning electron microscope taken before and after the contact with medium fluid, as well as the mechanical properties by tensile tests. In conclusion, it has been found that the cationic surface active agent, cetylpyridinium chloride reduced the lag time, observed during the release of model hydrophilic compound, as a result of its enhancing effect on wettability of tablets by reducing the contact angle between the medium fluid and the coating material. On the other hand, the anionic surface active agent, sodium lauryl sulphate has been inactivated possibly due to the interaction with model hydrophilic compound that has cationic properties and/or substances contained in membrane composition; thus, the lag time has not decreased and furthermore, a significant decrease in the delivery rate of model hydrophilic compound has been observed.

Persistence, Distribution, and Impact of Distinctly Segmented Microparticles on Cochlear Health following In Vivo Infusion3*

PubMed Central

Ross, Astin M.; Rahmani, Sahar; Prieskorn, Diane M.; Dishman, Acacia F; Miller, Josef M.; Lahann, Joerg; Altschuler, Richard A.

2016-01-01

Delivery of pharmaceuticals to the cochleae of patients with auditory dysfunction could potentially have many benefits from enhancing auditory nerve survival to protecting remaining sensory cells and their neuronal connections. Treatment would require platforms to enable drug delivery directly to the cochlea and increase the potential efficacy of intervention. Cochlear implant recipients are a specific patient subset that could benefit from local drug delivery as more candidates have residual hearing; and since residual hearing directly contributes to post-implantation hearing outcomes, it requires protection from implant insertion-induced trauma. This study assessed the feasibility of utilizing microparticles for drug delivery into cochlear fluids, testing persistence, distribution, biocompatibility, and drug release characteristics. To allow for delivery of multiple therapeutics, particles were composed of two distinct compartments; one containing polylactide-co-glycolide (PLGA), and one composed of acetal-modified dextran and PLGA. Following in vivo infusion, image analysis revealed microparticle persistence in the cochlea for at least 7 days post-infusion, primarily in the first and second turns. The majority of subjects maintained or had only slight elevation in auditory brainstem response thresholds at 7 days post-infusion compared to pre-infusion baselines. There was only minor to limited loss of cochlear hair cells and negligible immune response based on CD45+ immunolabling. When Piribedil-loaded microparticles were infused, Piribedil was detectable within the cochlear fluids at 7 days post-infusion. These results indicate that segmented microparticles are relatively inert, can persist, release their contents, and be functionally and biologically compatible with cochlear function and therefore are promising vehicles for cochlear drug delivery. PMID:26841263

Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems.

PubMed

Popilski, Hen; Stepensky, David

2015-05-01

Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies. The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed. Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.

Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of Poorly Soluble Drugs.

PubMed

Yasmin, Rokhsana; Rao, Shasha; Bremmell, Kristen E; Prestidge, Clive A

2016-07-01

Low dissolution of drugs in the intestinal fluid can limit their effectiveness in oral therapies. Here, a novel porous silica-supported solid lipid system was developed to optimize the oral delivery of drugs with limited aqueous solubility. Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica-supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica-A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles demonstrated significantly higher rate and extent of lipolysis in comparison with the pure solid lipid, depending on the lipid loading levels and the morphology. The highest lipid digestion was observed when silica-S was loaded with 34% (w/w) solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S formulation. Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided superior drug solubilization under simulated intestinal digesting condition in comparison with the drug-lipid suspension and drug-loaded silica. Therefore, solid lipid and nanoporous silica provides a synergistic effect on optimizing the solubilization of poorly water-soluble compound and the solid lipid-based porous carrier system provides a promising delivery approach to overcome the oral delivery challenges of poorly water-soluble drugs.

Hypodermoclysis therapy. In a chronic care hospital setting.

PubMed

Worobec, G; Brown, M K

1997-06-01

Occasionally, elderly patients experience acute, episodic incidents of illness that result in dehydration or a high potential for dehydration (e.g., flu, diarrhea). At times, patients may be unable, or refuse, to take fluids orally. Enteral routes via a nasogastric tube or enteral stomach tube may also not be available. In the past, these patients often had to be transferred from home or long-term care facilities to an acute care hospital for intravenous therapy. A transfer of the acutely ill elderly patient to an acute care hospital is often very stressful to the patient and his/her family and is costly to the health care delivery system. Hypodermoclysis, the process of rehydrating a patient by providing isotonic fluids into the subcutaneous tissues over a short time period, provides an alternative method to deal with acute, short-term fluid deficit problems in the elderly. Hypodermoclysis therapy can be administered in a chronic care setting thus potentially decreasing the need to transfer the elderly client to an acute care hospital. The purpose of this study was to investigate the use of hypodermoclysis therapy in solving acute, or potentially acute fluid deficit problems, that were anticipated to be both reversible and short term in nature. This was carried out in an elderly population that resided in a 284-bed chronic care hospital in southern Ontario.

Pseudotumor cerebri syndrome

MedlinePlus

... problems. Repeat lumbar punctures are helpful for pregnant women in order to delay surgery until after delivery. Other treatments may include: Fluid or salt restriction Medicines such as corticosteroids, acetazolamide, furosemide, and topiramate ...

Role of synbiotics in polysaccharide assisted colon targeted microspheres of mesalamine for the treatment of ulcerative colitis.

PubMed

Kaur, Rupinderjeet; Gulati, Monica; Singh, Sachin Kumar

2017-02-01

The present study explains the effect of concomitant administration of synbiotics with the polysaccharide based colon targeted delivery system. As the gut microflora get deranged on administration of mesalamine, drug release from such delivery systems is expected to be jeopardised because the release trigger is dependent solely on the colonic microbiota. To overcome this limitation, mesalamine was formulated as microspheres with guar gum and xanthan gum (prebiotics). These were combined with probiotics containing Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium longumand Saccharomyces boulardi. Dissolution studies of the prepared formulation conducted in simulated colonic fluid clearly demonstrated its superiority over the marketed, delayed release dosage forms of mesalamine. The therapeutic benefit of the concomitant administration of synbiotic with mesalamine was evidenced by the comparative evaluation of faecal contents, weight gain trend and histopathological studies conducted in rats. The results suggest that co-administration of synbiotics with mesalamine can be used as a convenient methodology to achieve efficient and cost-effective targeting of the drug to colon. Copyright © 2016 Elsevier B.V. All rights reserved.

Design and Implementation of a Characterization Test Rig for Evaluating High Bandwidth Liquid Fuel Flow Modulators

NASA Technical Reports Server (NTRS)

Saus, Joseph R.; Chang, Clarence T.; DeLaat, John C.; Vrnak, Daniel R.

2010-01-01

A test rig was designed and developed at the NASA Glenn Research Center (GRC) for the purpose of characterizing high bandwidth liquid fuel flow modulator candidates to determine their suitability for combustion instability control research. The test rig is capable of testing flow modulators at up to 600 psia supply pressure and flows of up to 2 gpm. The rig is designed to provide a quiescent flow into the test section in order to isolate the dynamic flow modulations produced by the test article. Both the fuel injector orifice downstream of the test article and the combustor are emulated. The effect of fuel delivery line lengths on modulator dynamic performance can be observed and modified to replicate actual fuel delivery systems. For simplicity, water is currently used as the working fluid, although future plans are to use jet fuel. The rig is instrumented for dynamic pressures and flows and a high-speed data system is used for dynamic data acquisition. Preliminary results have been obtained for one candidate flow modulator.

Liquid Methane Conditioning Capabilities Developed at the NASA Glenn Research Center's Small Multi- Purpose Research Facility (SMiRF) for Accelerated Lunar Surface Storage Thermal Testing

NASA Technical Reports Server (NTRS)

Bamberger, Helmut H.; Robinson, R. Craig; Jurns, John M.; Grasl, Steven J.

2011-01-01

Glenn Research Center s Creek Road Cryogenic Complex, Small Multi-Purpose Research Facility (SMiRF) recently completed validation / checkout testing of a new liquid methane delivery system and liquid methane (LCH4) conditioning system. Facility checkout validation was conducted in preparation for a series of passive thermal control technology tests planned at SMiRF in FY10 using a flight-like propellant tank at simulated thermal environments from 140 to 350K. These tests will validate models and provide high quality data to support consideration of LCH4/LO2 propellant combination option for a lunar or planetary ascent stage.An infrastructure has been put in place which will support testing of large amounts of liquid methane at SMiRF. Extensive modifications were made to the test facility s existing liquid hydrogen system for compatibility with liquid methane. Also, a new liquid methane fluid conditioning system will enable liquid methane to be quickly densified (sub-cooled below normal boiling point) and to be quickly reheated to saturation conditions between 92 and 140 K. Fluid temperatures can be quickly adjusted to compress the overall test duration. A detailed trade study was conducted to determine an appropriate technique to liquid conditioning with regard to the SMiRF facility s existing infrastructure. In addition, a completely new roadable dewar has been procured for transportation and temporary storage of liquid methane. A new spherical, flight-representative tank has also been fabricated for integration into the vacuum chamber at SMiRF. The addition of this system to SMiRF marks the first time a large-scale liquid methane propellant test capability has been realized at Glenn.This work supports the Cryogenic Fluid Management Project being conducted under the auspices of the Exploration Technology Development Program, providing focused cryogenic fluid management technology efforts to support NASA s future robotic or human exploration missions.

Comparison of intrapulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients.

PubMed

Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Couet, William; Mimoz, Olivier

2014-12-01

Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Comparison of Intrapulmonary and Systemic Pharmacokinetics of Colistin Methanesulfonate (CMS) and Colistin after Aerosol Delivery and Intravenous Administration of CMS in Critically Ill Patients

PubMed Central

Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Mimoz, Olivier

2014-01-01

Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. PMID:25267660

Can Glucose Be Monitored Accurately at the Site of Subcutaneous Insulin Delivery?

PubMed Central

Castle, Jessica R.; Jacobs, Peter G.; Cargill, Robert S.

2014-01-01

Because insulin promotes glucose uptake into adipocytes, it has been assumed that during measurement of glucose at the site of insulin delivery, the local glucose level would be much lower than systemic glucose. However, recent investigations challenge this notion. What explanations could account for a reduced local effect of insulin in the subcutaneous space? One explanation is that, in humans, the effect of insulin on adipocytes appears to be small. Another is that insulin monomers and dimers (from hexamer disassociation) might be absorbed into the circulation before they can increase glucose uptake locally. In addition, negative cooperativity of insulin action (a lower than expected effect of very high insulin concentrations)may play a contributing role. Other factors to be considered include dilution of interstitial fluid by the insulin vehicle and the possibility that some of the local decline in glucose might be due to the systemic effect of insulin. With regard to future research, redundant sensing units might be able to quantify the effects of proximity, leading to a compensatory algorithm. In summary, when measured at the site of insulin delivery, the decline in subcutaneous glucose level appears to be minimal, though the literature base is not large. Findings thus far support (1) the development of integrated devices that monitor glucose and deliver insulin and (2) the use of such devices to investigate the relationship between subcutaneous delivery of insulin and its local effects on glucose. A reduction in the number of percutaneous devices needed to manage diabetes would be welcome. PMID:24876621

Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).

PubMed

Johnston, Kimberly A; Westover, Angela J; Rojas-Pena, Alvaro; Buffington, Deborah A; Pino, Christopher J; Smith, Peter L; Humes, H David

2017-11-01

Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 × 10 8 renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Magnetic drug targeting through a realistic model of human tracheobronchial airways using computational fluid and particle dynamics.

PubMed

Pourmehran, Oveis; Gorji, Tahereh B; Gorji-Bandpy, Mofid

2016-10-01

Magnetic drug targeting (MDT) is a local drug delivery system which aims to concentrate a pharmacological agent at its site of action in order to minimize undesired side effects due to systemic distribution in the organism. Using magnetic drug particles under the influence of an external magnetic field, the drug particles are navigated toward the target region. Herein, computational fluid dynamics was used to simulate the air flow and magnetic particle deposition in a realistic human airway geometry obtained by CT scan images. Using discrete phase modeling and one-way coupling of particle-fluid phases, a Lagrangian approach for particle tracking in the presence of an external non-uniform magnetic field was applied. Polystyrene (PMS40) particles were utilized as the magnetic drug carrier. A parametric study was conducted, and the influence of particle diameter, magnetic source position, magnetic field strength and inhalation condition on the particle transport pattern and deposition efficiency (DE) was reported. Overall, the results show considerable promise of MDT in deposition enhancement at the target region (i.e., left lung). However, the positive effect of increasing particle size on DE enhancement was evident at smaller magnetic field strengths (Mn [Formula: see text] 1.5 T), whereas, at higher applied magnetic field strengths, increasing particle size has a inverse effect on DE. This implies that for efficient MTD in the human respiratory system, an optimal combination of magnetic drug career characteristics and magnetic field strength has to be achieved.

Soy Protein Microparticles for Enhanced Oral Ibuprofen Delivery: Preparation, Characterization, and In Vitro Release Evaluation.

PubMed

Anaya Castro, Maria Antonieta; Alric, Isabelle; Brouillet, Fabien; Peydecastaing, Jérôme; Fullana, Sophie Girod; Durrieu, Vanessa

2018-04-01

The objective of this work was to evaluate soy protein isolate (SPI) and acylated soy protein (SPA) as spray-drying encapsulation carriers for oral pharmaceutical applications. SPI acylation was performed by the Schotten-Baumann reaction. SPA, with an acylation rate of 41%, displayed a decrease in solubility in acidic conditions, whereas its solubility was unaffected by basic conditions. The drug encapsulation capacities of both SPI and SPA were tested with ibuprofen (IBU) as a model poorly soluble drug. IBU-SPI and IBU-SPA particles were obtained by spray-drying under eco-friendly conditions. Yields of 70 to 87% and microencapsulation efficiencies exceeding 80% were attained for an IBU content of 20 to 40% w/w, confirming the excellent microencapsulation properties of SPI and the suitability of the chemical modification. The in vitro release kinetics of IBU were studied in simulated gastrointestinal conditions (pH 1.2 and pH 6.8, 37°C). pH-sensitive release patterns were observed, with an optimized low rate of release in simulated gastric fluid for SPA formulations, and a rapid and complete release in simulated intestinal fluid for both formulations, due to the optimal pattern of pH-dependent solubility for SPA and the molecular dispersion of IBU in soy protein. These results demonstrate that SPI and SPA are relevant for the development of pH-sensitive drug delivery systems for the oral route.

Preparation of theophylline-hydroxypropylmethylcellulose matrices using supercritical antisolvent precipitation: a preliminary study.

PubMed

Moneghini, M; Perissutti, B; Kikic, I; Grassi, M; Cortesi, A; Princivalle, F

2006-01-01

Several controlled release systems of drugs have been elaborated using a supercritical fluid process. Indeed, recent techniques using a supercritical fluid as a solvent or as an antisolvent are considered to be useful alternatives to produce fine powders. In this preliminary study, the effect of Supercritical Anti Solvent process (SAS) on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC) was investigated. Two grades of HPMC (HPMC E5 and K100) as carriers were considered in order to prepare a sustained delivery system for theophylline which was used as a model drug. The characterization of the drug before and after SAS treatment, and the coprecipitates with carriers, was performed by X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The dissolution rate of theophylline, theophylline-coprecipitates, and matricial tablets prepared with coprecipitates were determined. The physical characterizations revealed a substantial correspondence of the drug solid state before and after supercritical fluid treatment while drug-polymer interactions in the SAS-coprecipitates were attested. The dissolution studies of the matrices prepared compressing the coprecipitated systems showed that the matrices based on HPMC K100 were able to promote a sustained release of the drug. Further, this advantageous dissolution performance was found to be substantially independent of the pH of the medium. The comparison with the matrices prepared with untreated substances demonstrated that matrices obtained with SAS technique can provide a slower theophylline release rate. A new mathematical model describing the in vitro dissolution kinetics was proposed and successfully tested on these systems.

Investigation of Flow in a Centrifugal Pump

NASA Technical Reports Server (NTRS)

Fischer, Karl

1946-01-01

The investigation of the flow in a centrifugal pump indicated that the flow patterns in frictional fluid are fundamentally different from those in frictionless fluid. In particular, the dead air space adhering to the section side undoubtedly causes a reduction of the theoretically possible delivery head. The velocity distribution over a parallel circle is also subjected to a noticeable change as a result of the incomplete filling of the passages. The relative velocity on the pressure side of the vane, which for passages completely filled with active flow would differ little from zero even at comparatively lower than normal delivery volume, is increased, so that no rapid reverse flow occurs on the pressure side of the vane even for smaller delivery volume. It was established, further, that the flow ceases to be stationary for very small quantities of water. The inflow to the impeller can be regarded as radial for the operating range an question. The velocity triangles at the exit are subjected to a significant alteration in shape ae a result of the increased peripheral velocity, which may be of particular importance in the determination of the guide vane entrance angle.

Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin.

PubMed

Li, Lei; Jiang, Guohua; Yu, Weijiang; Liu, Depeng; Chen, Hua; Liu, Yongkun; Tong, Zaizai; Kong, Xiangdong; Yao, Juming

2017-01-01

To overcome multiple barriers for oral delivery of insulin, the chitosan-based multifunctional nanocarriers modified by L-valine (LV, used as a target ligand to facilitate the absorption of the small intestine) and phenylboronic acid (PBA, used as a glucose-responsive unit) have been designed and evaluated in this study. The resultant nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that L-valine modified chitosan-based multifunctional nanocarriers may be a promising drug delivery carrier for oral administration of insulin. Copyright © 2016 Elsevier B.V. All rights reserved.

Recovery of Drug Delivery Nanoparticles from Human Plasma using an Electrokinetic Platform Technology

PubMed Central

Ibsen, Stuart; Sonnenberg, Avery; Schutt, Carolyn; Mukthavaram, Rajesh; Yeh, Yasan; Ortac, Inanc; Manouchehri, Sareh; Kesari, Santosh; Esener, Sadik

2015-01-01

The effect of complex biological fluids on the surface and structure of nanoparticles is a rapidly expanding field of study. One of the challenges holding back this research is the difficulty of recovering therapeutic nanoparticles from biological samples due to their small size, low density, and stealth surface coatings. Here we present the first demonstration of the recovery and analysis of drug delivery nanoparticles from undiluted human plasma samples through the use of a new electrokinetic platform technology. The particles are recovered from plasma through a dielectrophoresis separation force that is created by innate differences in the dielectric properties between the unaltered nanoparticles and the surrounding plasma. We show this can be applied to a wide range of drug delivery nanoparticles of different morphologies and materials, including low density nano-liposomes. These recovered particles can then be analyzed using different methods including scanning electron microscopy to monitor surface and structural changes that result from plasma exposure. We believe that this new recovery technique is broadly applicable to the recovery of nanoparticles from high conductance fluids in a wide range of applications. PMID:26274918

Inhalational System for Etoposide Liposomes: Formulation Development and In Vitro Deposition

PubMed Central

Parmar, J. J.; Singh, D. J.; Lohade, A. A.; Hegde, Darshana D.; Soni, P. S.; Samad, A.; Menon, Mala D.

2011-01-01

Etoposide is a semisynthetic compound, widely used in treatment of non small cell lung cancer. However, frequent dosing and adverse effects remain a major concern in the use of etoposide. Liposomal systems for pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of etoposide was prepared by film hydration method. Various parameters were optimized with respect to entrapment efficiency as well as particle size of etoposide liposomes. For better shelf life of etoposide liposomes, freeze drying using trehalose as cryoprotectant was carried out. The liposomes were characterized for entrapment efficiency, particle size, surface topography, and in vitro drug release was carried out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±4°). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes. PMID:23112400

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.

Engineering strategies for the design of plant nutrient delivery systems for use in space: approaches to countering microbiological contamination

NASA Technical Reports Server (NTRS)

Gonzales, A. A.; Schuerger, A. C.; Barford, C.; Mitchell, R.

1996-01-01

Microbiological contamination of crops within space-based plant growth research chambers has been postulated as a potentially significant problem. Microbial infestations; fouling of Nutrient Delivery System (NDS) fluid loops; and the formation of biofilms have been suggested as the most obvious and important manifestations of the problem. Strict sanitation and quarantine procedures will reduce, but not eliminate, microbial species introduced into plant growth systems in space habitats. Microorganisms transported into space most likely will occur as surface contaminants on spacecraft components, equipment, the crew, and plant-propagative materials. Illustrations of the potential magnitude of the microbiological contamination issue will be drawn from the literature and from documentation of laboratory and commercial field experience. Engineering strategies for limiting contamination and for the development of countermeasures will be described. Microbiological control technologies and NDS hardware will be discussed. Configurations appropriate for microgravity research facilities, as well as anticipated bio-regenerative life support system implementations, will be explored. An efficiently designed NDS, capable of adequately meeting the environmental needs of crop plants in space, is considered to be critical in both the research and operational domains. Recommended experiments, tests, and technology developments, structured to allow the development of prudent engineering solutions also will be presented.

Engineering Strategies for the Design of Plant Nutrient Delivery Systems for Use in Space: Approaches to Countering Microbiological Contamination

NASA Technical Reports Server (NTRS)

Gonzales, A. A.; Schuerger, A. C.; Mitchell, R.; Harper, Lynn D. (Technical Monitor)

1994-01-01

Microbiological contamination of crops within space-based crop growth research chambers has been postulated as a potentially significant problem. Microbial infestations; fouling of Nutrient Delivery System (NDS) fluid loops; and the formation of biofilms, have been suggested as the most obvious and important manifestations of the problem. Strict sanitation and quarantine procedures will reduce, but not eliminate, microbial species introduced into plant growing systems in space habitats. Microorganisms transported into space will most likely occur as contaminants on spacecraft components, equipment, the crew, and plant-propagative materials. Illustrations of the potential magnitude of the microbiological contamination issue will be drawn from the literature and from documentation of laboratory and commercial field experience. Engineering strategies for limiting contamination and for the development of countermeasures will be described. Microbiological control technologies and NDS hardware will be discussed. Configurations appropriate for microgravity research facilities, as well as anticipated bio-regenerative life support system implementations, will be explored. An efficiently designed NDS, capable of adequately meeting the environmental needs of crop plants in space, is considered to be critical in both the research and operational domains. Recommended experiments, tests and technology developments, structured to allow the development of prudent engineering solutions, will also be presented.

The use of miniature supersonic nozzles for microparticle acceleration: a numerical study.

PubMed

Liu, Y

2007-10-01

By means of a high-speed gas flow generated by a miniature supersonic nozzle, we proposed a unique biolistic method to accelerate microparticle formulation of drugs to sufficient momentum, to penetrate the outer layer of human skin or mucosal tissue for the treatment of a range of diseases. One of the main concerns for designing and evaluating this system is ensuring microparticles delivery into human skin with a controllable velocity range and spatial distribution. The initial experimental work suggested that the performance of the transdermal delivery strongly depends on aerodynamics of the supersonic nozzles employed. In this paper, computational fluid dynamics (CFD) is utilized to characterize existing prototype biolistic delivery systems, the device with a converging-diverging supersonic nozzle (CDSN) and the device based on the contoured-shock-tube (CST) design, with the aim at investigating the transient gas and particle dynamics in the supersonic nozzles. Whenever possible, predicted pressure and Mach number histories, 2-D flow structures, and particle velocity distributions are made to compare with the corresponding experimental measurements to validate the implemented numerical approach. The gas-particle interaction and performance of two biolistic devices are interrogated and distinguished. Subsequently, the particle impact conditions are presented and discussed. It is demonstrated that the CST can deliver microparticles with a narrow and more controllable velocity range and spatial distribution.

Oil cooling system for a gas turbine engine

NASA Technical Reports Server (NTRS)

Coffinberry, G. A.; Kast, H. B. (Inventor)

1977-01-01

A gas turbine engine fuel delivery and control system is provided with means to recirculate all fuel in excess of fuel control requirements back to aircraft fuel tank, thereby increasing the fuel pump heat sink and decreasing the pump temperature rise without the addition of valving other than that normally employed. A fuel/oil heat exchanger and associated circuitry is provided to maintain the hot engine oil in heat exchange relationship with the cool engine fuel. Where anti-icing of the fuel filter is required, means are provided to maintain the fuel temperature entering the filter at or above a minimum level to prevent freezing thereof. Fluid circuitry is provided to route hot engine oil through a plurality of heat exchangers disposed within the system to provide for selective cooling of the oil.

Hybrid macro-micro fluidics system for a chip-based biosensor

NASA Astrophysics Data System (ADS)

Tamanaha, C. R.; Whitman, L. J.; Colton, R. J.

2002-03-01

We describe the engineering of a hybrid fluidics platform for a chip-based biosensor system that combines high-performance microfluidics components with powerful, yet compact, millimeter-scale pump and valve actuators. The microfluidics system includes channels, valveless diffuser-based pumps, and pinch-valves that are cast into a poly(dimethylsiloxane) (PDMS) membrane and packaged along with the sensor chip into a palm-sized plastic cartridge. The microfluidics are driven by pump and valve actuators contained in an external unit (with a volume ~30 cm3) that interfaces kinematically with the PDMS microelements on the cartridge. The pump actuator is a simple-lever, flexure-hinge displacement amplifier that increases the motion of a piezoelectric stack. The valve actuators are an array of cantilevers operated by shape memory alloy wires. All components can be fabricated without the need for complex lithography or micromachining, and can be used with fluids containing micron-sized particulates. Prototypes have been modeled and tested to ensure the delivery of microliter volumes of fluid and the even dispersion of reagents over the chip sensing elements. With this hybrid approach to the fluidics system, the biochemical assay benefits from the many advantages of microfluidics yet we avoid the complexity and unknown reliability of immature microactuator technologies.

Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared with 8% hypertonic NACl in sheep with multiple hemorrhages.

PubMed

do Nascimento, Paulo; Vaid, Sumreen U; Hoskins, Stephen L; Espana, Jonathan M; Kinsky, Michael P; Kramer, George C

2007-05-01

Initial fluid resuscitation of hemorrhagic shock might be enhanced by the infusion of monocarboxylate-energy substrates. We evaluated hemodynamics, metabolism, and fluid dynamics for initial resuscitation of hemorrhage using small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched 8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70 to T75. Fluid resuscitation from T30 to T180 was performed by a computer-controlled closed-loop system, which titrated infusion rate to a mean arterial pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed by the administration of lactated Ringer. Both HPY and HS restored cardiac index similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was significantly higher (T180), whereas oxygen delivery was significantly lower (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 +/- 6.2 mL/kg for HPY and 39.4 +/- 6.8 mL/kg for HS. Plasma volume was similarly increased and approached baseline values for both groups. Initial resuscitation with small volume HPY offered no hemodynamic or metabolic advantage compared with small volume HS when the fluids were infused to an end point pressure.

Comparative study of Eyring and Carreau fluids in a suspension of dust and nickel nanoparticles with variable conductivity

NASA Astrophysics Data System (ADS)

Mamatha Upadhya, S.; Mahesha; Raju, C. S. K.

2018-04-01

A theoretical analysis is carried out to investigate the magnetohydrodynamic unsteady flow of Eyring-Powell and Carreau non-Newtonian fluids in a suspension of dust and nickel nanoparticles by considering variable thermal conductivity and thermal radiation. Dispersion of nickel nanoparticles in dusty fluids finds applications in heat exchanger systems, rechargeable batteries, chemical catalysts, metallurgy, conducting paints, magnetic recording media, drug delivery, nanofibers, textiles, etc. The initially arising set of physical governing partial differential equations is transformed to ordinary differential equations (ODEs) with the aid of similarity transformations. Consequentially, the nonlinear ODEs are solved numerically through the Runge-Kutta Fehlberg scheme (RKFS). The computational results for non-dimensional temperature and velocity profiles are presented through graphs. Furthermore, the numerical values of friction factor and heat transfer rate are tabulated numerically for the unsteady and steady cases of the Eyring and Carreau fluid cases and of the dusty non-Newtonian (φ=0) and the dusty non-Newtonian nanofluid (φ≠ 0) cases of the unsteady flow. We also validated the present results with previous published studies and found them to be highly satisfactory. The formulated model reveals that the rate of heat transfer is higher in the mixture of the nickel + Eyring-Powell case compared to the nickel + Carreau case. From this we can highlight that, depending on the industrial appliances, we can use heating or cooling processes for Eyring and Carreau fluids, respectively.

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…

Drug injection into fat tissue with a laser based microjet injector

NASA Astrophysics Data System (ADS)

Han, Tae-hee; Hah, Jung-moo; Yoh, Jack J.

2011-05-01

We have investigated a new micro drug jet injector using laser pulse energy. An infrared laser beam of high energy (˜3 J/pulse) is focused inside a driving fluid in a small chamber. The pulse then induces various energy releasing processes, and generates fast microjets through a micronozzle. The elastic membrane of this system plays an important role in transferring mechanical pressure and protecting drug from heat release. In this paper, we offer the sequential images of microjet generation taken by a high speed camera as an evidence of the multiple injections via single pulse. Furthermore, we test the proposed system to penetrate soft animal tissues in order to evaluate its feasibility as an advanced transdermal drug delivery method.

Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation.

PubMed

Achariyar, Thiyagaragan M; Li, Baoman; Peng, Weiguo; Verghese, Philip B; Shi, Yang; McConnell, Evan; Benraiss, Abdellatif; Kasper, Tristan; Song, Wei; Takano, Takahiro; Holtzman, David M; Nedergaard, Maiken; Deane, Rashid

2016-12-08

Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation. We used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test. We show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state. Thus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term.

Injectable, in situ forming poly(propylene fumarate)-based ocular drug delivery systems.

PubMed

Ueda, H; Hacker, M C; Haesslein, A; Jo, S; Ammon, D M; Borazjani, R N; Kunzler, J F; Salamone, J C; Mikos, A G

2007-12-01

This study sought to develop an injectable formulation for long-term ocular delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug and the biodegradable polymer poly(propylene fumarate) (PPF) in the biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon injection of the solution into an aqueous environment, a FA-loaded PPF matrix is precipitated in situ through the diffusion/extraction of NMP into surrounding aqueous fluids. Fabrication of the matrices and in vitro release studies were performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5% were achieved. High performance liquid chromatography was employed to determine the released amount of FA. The effects of drug loading, PPF content of the injectable formulation, and additional photo-crosslinking of the matrix surface were investigated. Overall, FA release was sustained in vitro over up to 400 days. After an initial burst release of 22 to 68% of initial FA loading, controlled drug release driven by diffusion and bulk erosion was observed. Drug release rates in a therapeutic range were demonstrated. Release kinetics were found to be dependent on drug loading, formulation PPF content, and extent of surface crosslinking. The results suggest that injectable, in situ formed PPF matrices are promising candidates for the formulation of long-term, controlled delivery devices for intraocular drug delivery. Copyright 2007 Wiley Periodicals, Inc.

Microbial diversity within Juan de Fuca ridge basement fluids sampled from oceanic borehole observatories

NASA Astrophysics Data System (ADS)

Jungbluth, S.; Bowers, R.; Lin, H.; Hsieh, C.; Cowen, J. P.; Rappé, M.

2012-12-01

Three generations of sampling and instrumentation platforms known as Circulation Obviation Retrofit Kit (CORK) observatories affixed to Ocean Drilling Program (ODP) and Integrated Ocean Drilling Program (IODP) boreholes are providing unrivaled access to fluids originating from 1.2-3.5 million-years (Myr) old basaltic crust of the eastern flank of the Juan de Fuca ridge. Borehole fluid samples obtained via a custom seafloor fluid pumping and sampling system coupled to CORK continuous fluid delivery lines are yielding critical insights into the biogeochemistry and nature of microbial life inhabiting the sediment-covered basement environment. Direct microscopic enumeration revealed microbial cell abundances that are 2-41% of overlying bottom seawater. Snapshots of basement fluid microbial diversity and community structure have been obtained through small subunit ribosomal RNA (SSU rRNA) gene cloning and sequencing from five boreholes that access a range of basement ages and temperatures at the sediment-basement interface. SSU rRNA gene clones were derived from four different CORK installations (1026B, 1301A, 1362A, and 1362B) accessing relatively warmer (65°C) and older (3.5 Myr) ridge flank, and one location (1025C) accessing relatively cooler (39°C) and younger (1.2 Myr) ridge flank, revealing that warmer basement fluids had higher microbial diversity. A sampling time-series collected from borehole 1301A has revealed a microbial community that is temporally variable, with the dominant lineages changing between years. Each of the five boreholes sampled contained a unique microbial assemblage, however, common members are found from both cultivated and uncultivated lineages within the archaeal and bacterial domains, including meso- and thermophilic microbial lineages involved with sulfur cycling (e.g Thiomicrospira, Sulfurimonas, Desulfocapsa, Desulfobulbus). In addition, borehole fluid environmental gene clones were also closely related to uncultivated lineages recovered from both terrestrial and marine hydrothermal systems (e.g. Candidatus Desulforudis, Candidate Phylum OP8) as well as globally distributed marine sediments (e.g. Miscellaneous Crenarchaeotic Group, JTB35). This analysis provides a framework for future research investigating the evolutionary and functional diversity, population genetics, and activity of the poorly understood habitat. These ongoing sampling expeditions greatly benefit from improvements to both CORK observatories and evolving sampling equipment including microbiologically-friendly materials and dependable access to pristine fluids from the ocean crust.

Hydrodynamically-driven drug release during interstitial flow through hollow fibers implanted near lymphatics

PubMed Central

Dukhin, Stanislav S.; Labib, Mohamed E.

2016-01-01

Current drug delivery devices (DDD) are mainly based on the use of diffusion as the main transport process. Diffusion-driven processes can only achieve low release rate because diffusion is a slow process. This represents a serious obstacle in the realization of recent successes in the suppression of lymphatic metastasis and in the prevention of limb and organ transplant rejection. Surprisingly, it was overlooked that there is a more favorable drug release mode which can be achieved when a special DDD is implanted near lymphatics. This opportunity can be realized when the interstitial fluid flow penetrates a drug delivery device of proper design and allows such fluid to flow out of it. This design is based on hollow fibers loaded with drug and whose hydrodynamic permeability is much higher than that of the surrounding tissue. The latter is referred to as hollow fiber of high hydrodynamic permeability (HFHP). The interstitial flow easily penetrates the hollow fiber membrane as well as its lumen with a higher velocity than that in the adjacent tissue. The interstitial liquid stream entering the lumen becomes almost saturated with drug as it flows out of the HFHP. This is due to the drug powder dissolution in the lumens of HFHP which forms a strip of drug solution that crosses the interstitium and finally enters the lymphatics. This hydrodynamically-driven release (HDR) may exceed the concomitant diffusion-driven release (DDR) by one or even two orders of magnitude. The hydrodynamics of the two-compartment media is sufficient for developing the HDR theory which is detailed in this paper. Convective diffusion theory for two compartments (membrane of hollow fiber and adjacent tissue) is required for exact quantification when a small contribution of DDR to predominating HDR is present. Hence, modeling is important for HDR which would lead to establishing a new branch in physico-chemical hydrodynamics. The release rate achieved with the use of HFHP increases proportional to the number of hollow fibers in the fabric employed in drug delivery. Based on this contribution, it is now possible to simultaneously provide high release rates and long release durations, thus overcoming a fundamental limitation in drug delivery. Perhaps this breakthrough in long-term drug delivery has potential applications in targeting lymphatics and in treating cancer and cancer metastasis without causing the serious side effects of systemic drugs. PMID:28579697

[Intrapartum amnioinfusion in patients with meconium-stained amniotic fluid].

PubMed

Engel, Karina; Samborska, Monika; Bilar, Marek; Sipak-Szmigiel, Olimpia; Ronin-Walknowska, Elzbieta

2008-09-01

The aim of the study was to evaluate the effect of intrapartum amnioinfusion in the presence of meconium stained amniotic fluid. 93 women with meconium-stained amniotic fluid were assigned to receive amnioinfusion or no amnioinfusion (128 women). The trials were evaluated for fetal distress syndrome, route of delivery, fetal acidemia, Apgar score at 1 and 5 min., meconium aspiration syndrome, postpartum endometritis and maternal hospital stays. Amnioinfusion in cases of meconium-stained fluid did not improve the number of fetal distress symptoms during fetal heart rate monitoring. Amnioinfusion was associated with a significant decrease of neonatal acidemia although it did not improve Apgar score. In our study amnioinfusion was not associated with reduction in the incidence of neonatal outcome and puerperial complications.

Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms.

PubMed

Fekri, Farnaz; Delos Santos, Ralph Christian; Karshafian, Raffi; Antonescu, Costin N

2016-01-01

Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB) is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME) for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR), and distinct mechanism(s) that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may improve targeted drug delivery.

Controlled release of optimized electroporation enhances the transdermal efficiency of sinomenine hydrochloride for treating arthritis in vitro and in clinic

PubMed Central

Feng, Shun; Zhu, Lijun; Huang, Zhisheng; Wang, Haojia; Li, Hong; Zhou, Hua; Lu, Linlin; Wang, Ying; Liu, Zhongqiu; Liu, Liang

2017-01-01

Sinomenine hydrochloride (SH) is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration. PMID:28670109

Tuberculous meningoencephalitis associated with brain tuberculomas during pregnancy: a case report.

PubMed

Namani, Sadie; Dreshaj, Shemsedin; Berisha, Arieta Zogaj

2017-06-29

Tuberculous meningitis is globally highly prevalent and is commoner in resource-limited countries and in patients with immunosuppression. Central nervous system tuberculosis is one of the severest forms of extrapulmonary tuberculosis during pregnancy and associated brain tuberculomas have been rarely reported. With the availability of neuroimaging at our hospital center, we present the first case of tuberculous meningoencephalitis associated with brain tuberculomas during pregnancy. In this case report we present a 25-year-old, Albanian, pregnant woman living in an urban area in Kosovo, who at 24 weeks of twin pregnancy manifested signs and symptoms of meningoencephalitis with decreased level of consciousness, hemiparesis, and generalized recurrent seizures. Based on medical history, origin from a region of high prevalence of tuberculosis, clinical presentation, especially neurological examination, cytobiochemical changes in cerebrospinal fluid (mild mononuclear pleocytosis with decreased level of glucose and elevated proteins), and elevated level of interferon-gamma release assay in cerebrospinal fluid, antituberculous therapy was initiated on the fourth day of admission. After 3 weeks of treatment, at 27 weeks of pregnancy, she had a preterm delivery and both twins, with low birthweight, died after 24 and 72 hours. Although findings on chest radiography were normal, brain magnetic resonance imaging showed signs of meningoencephalitis and multiple intracerebral tuberculomas, while Koch's bacillus was isolated from urine cultures. On long-term follow-up after delivery, she was cured with no sequelae and became pregnant again without any additional complications. In countries with a high prevalence of tuberculosis, screening for central nervous system tuberculosis should be considered in the differential diagnosis of meningitis in pregnancy. Cerebral imaging is essential to establish the diagnosis of brain tuberculomas in such a case of suspected tuberculous meningoencephalitis during pregnancy.

Numerical simulations of targeted delivery of magnetic drug aerosols in the human upper and central respiratory system: a validation study.

PubMed

Kenjereš, Saša; Tjin, Jimmy Leroy

2017-12-01

In the present study, we investigate the concept of the targeted delivery of pharmaceutical drug aerosols in an anatomically realistic geometry of the human upper and central respiratory system. The geometry considered extends from the mouth inlet to the eighth generation of the bronchial bifurcations and is identical to the phantom model used in the experimental studies of Banko et al. (2015 Exp. Fluids 56 , 1-12 (doi:10.1007/s00348-015-1966-y)). In our computer simulations, we combine the transitional Reynolds-averaged Navier-Stokes (RANS) and the wall-resolved large eddy simulation (LES) methods for the air phase with the Lagrangian approach for the particulate (aerosol) phase. We validated simulations against recently obtained magnetic resonance velocimetry measurements of Banko et al. (2015 Exp. Fluids 56 , 1-12. (doi:10.1007/s00348-015-1966-y)) that provide a full three-dimensional mean velocity field for steady inspiratory conditions. Both approaches produced good agreement with experiments, and the transitional RANS approach is selected for the multiphase simulations of aerosols transport, because of significantly lower computational costs. The local and total deposition efficiency are calculated for different classes of pharmaceutical particles (in the 0.1 μm≤ d p ≤10 μm range) without and with a paramagnetic core (the shell-core particles). For the latter, an external magnetic field is imposed. The source of the imposed magnetic field was placed in the proximity of the first bronchial bifurcation. We demonstrated that both total and local depositions of aerosols at targeted locations can be significantly increased by an applied magnetization force. This finding confirms the possible potential for further advancement of the magnetic drug targeting technique for more efficient treatments for respiratory diseases.

Remedial Amendment Delivery near the Water Table Using Shear Thinning Fluids: Experiments and Numerical Simulations

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

Oostrom, Martinus; Truex, Michael J.; Vermeul, Vincent R.

2014-08-19

The use of shear thinning fluids (STFs) containing xanthan is a potential enhancement for emplacing a solute amendment near the water table and within the capillary fringe. Most research to date related to STF behavior has involved saturated and confined conditions. A series of flow cell experiments were conducted to investigate STF emplacement in variable saturated homogeneous and layered heterogeneous systems. Besides flow visualization using dyes, amendment concentrations and pressure data were obtained at several locations. The experiments showed that injection of STFs considerably improved the subsurface distribution near the water table by mitigating preferential flow through higher permeability zonesmore » compared to no-polymer injections. The phosphate amendment migrated with the xanthan SFT without retardation. Despite the high viscosity of the STF, no excessive mounding or preferential flow were observed in the unsaturated zone. The STOMP simulator was able to predict the experimentally observed fluid displacement and amendment concentrations reasonably well. Cross flow between layers could be interpreted as the main mechanism to transport STFs into lower permeability layers based on the observed pressure gradient and concentration data in layers of differing hydraulic conductivity.« less

Immunopotentiating reconstituted influenza virus virosome vaccine delivery system for immunization against hepatitis A.

PubMed Central

Glück, R; Mischler, R; Brantschen, S; Just, M; Althaus, B; Cryz, S J

1992-01-01

Hepatitis A virus (HAV) was purified from MRC-5 human diploid cell cultures, inactivated with formalin, and evaluated for safety and immunogenicity in humans. Three vaccine formulations were produced: (a) a fluid preparation containing inactivated HAV, (b) inactivated HAV adsorbed to Al(OH)3, and (c) inactivated HAV coupled to novel immunopotentiating reconstituted influenza virosomes (IRIV). IRIV were prepared by combining phosphatidylcholine, phosphatidylethanolamine, phospholipids originating from the influenza virus envelope, influenza virus hemagglutinin, and neuraminidase. The HAV-IRIV appeared as unilamellar vesicles with a diameter of approximately 150 nm when viewed by transmission electron microscopy. Upon intramuscular injection, the alum-adsorbed vaccine was associated with significantly (P < 0.01) more local adverse reactions than either the fluid or IRIV formulations. 14 d after a single dose of vaccine, all the recipients of the IRIV formulation seroconverted (> or = 20 mIU/ml) versus 30 and 44% for those who received the fluid and alum-adsorbed vaccines, respectively (P < 0.001). The geometric mean anti-HAV antibody titer achieved after immunization with the IRIV-HAV vaccine was also significantly higher (P < 0.005) compared with the other two vaccines. Images PMID:1334977

Design and process aspects of laboratory scale SCF particle formation systems.

PubMed

Vemavarapu, Chandra; Mollan, Matthew J; Lodaya, Mayur; Needham, Thomas E

2005-03-23

Consistent production of solid drug materials of desired particle and crystallographic morphologies under cGMP conditions is a frequent challenge to pharmaceutical researchers. Supercritical fluid (SCF) technology gained significant attention in pharmaceutical research by not only showing a promise in this regard but also accommodating the principles of green chemistry. Given that this technology attained commercialization in coffee decaffeination and in the extraction of hops and other essential oils, a majority of the off-the-shelf SCF instrumentation is designed for extraction purposes. Only a selective few vendors appear to be in the early stages of manufacturing equipment designed for particle formation. The scarcity of information on the design and process engineering of laboratory scale equipment is recognized as a significant shortcoming to the technological progress. The purpose of this article is therefore to provide the information and resources necessary for startup research involving particle formation using supercritical fluids. The various stages of particle formation by supercritical fluid processing can be broadly classified into delivery, reaction, pre-expansion, expansion and collection. The importance of each of these processes in tailoring the particle morphology is discussed in this article along with presenting various alternatives to perform these operations.

Supercritical fluid processing of drug nanoparticles in stable suspension.

PubMed

Pathak, Pankaj; Meziani, Mohammed J; Desai, Tarang; Foster, Charles; Diaz, Julian A; Sun, Ya-Ping

2007-07-01

Significant effort has been directed toward the development of drug formulation and delivery techniques, especially for the drug of no or poor aqueous solubility. Among various strategies to address the solubility issue, the reduction of drug particle sizes to the nanoscale has been identified as a potentially effective and broadly applicable approach. Complementary to traditional methods, supercritical fluid techniques have found unique applications in the production and processing of drug particles. Here we report the application of a newly developed supercritical fluid processing technique, Rapid Expansion of a Supercritical Solution into a Liquid Solvent, to the nanosizing of potent antiparasitic drug Amphotericin B particles. A supercritical carbon dioxide-cosolvent system was used for the solubilization and processing of the drug. The process produced well-dispersed nanoscale Amphotericin B particles suspended in an aqueous solution, and the suspension was intrinsically stable or could be further stabilized in the presence of water-soluble polymers. The properties of the drug nanoparticles were found to be dependent on the type of cosolvent used. The results on the use of dimethyl sulfoxide and methanol as cosolvents and their effects on the properties of nanosized Amphotericin B particles are presented and discussed.

Solvent exchange-induced in situ forming gel comprising ethyl cellulose-antimicrobial drugs.

PubMed

Phaechamud, Thawatchai; Mahadlek, Jongjan

2015-10-15

Solvent-exchanged in situ forming gel is a drug delivery system which is in sol form before administration. When it contacts with the body fluid, then the water miscible organic solvent dissipates and water penetrates into the system, leading the polymer precipitation as in situ gel at the site of injection. The aim of this research was to study the parameters affecting the gel properties, drug release and antimicrobial activities of the in situ forming gels prepared from ethyl cellulose (EC) dissolved in N-methyl pyrrolidone (NMP) to deliver the antimicrobial agents (doxycycline hyclate, metronidazole and benzyl peroxide) for periodontitis treatment. The gel appearance, pH, viscosity, rheology, syringeability, gel formation, rate of water diffusion into the gels, in vitro degradation, drug release behavior and antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans and Porphyrommonas gingivalis were determined. Increasing the amount of EC increased the viscosity of system while still exhibiting Newtonian flow and increased the work of syringeability whereas decreased the releasing of drug. The system transformed into the rigid gel formation after being injected into the simulated gingival crevicular fluid. The developed systems containing 5% w/w antimicrobial agent showed the antimicrobial activities against all test bacteria. Thus the developed solvent exchange-induced in situ forming gels comprising EC-antimicrobial drugs exhibited potential use for periodontitis treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

Simulation of Complex Transport of Nanoparticles around a Tumor Using Tumor-Microenvironment-on-Chip

PubMed Central

Kwak, Bongseop; Ozcelikkale, Altug; Shin, Crystal S.; Park, Kinam; Han, Bumsoo

2014-01-01

Delivery of therapeutic agents selectively to tumor tissue, which is referred as “targeted delivery,” is one of the most ardently pursued goals of cancer therapy. Recent advances in nanotechnology enable numerous types of nanoparticles (NPs) whose properties can be designed for targeted delivery to tumors. In spite of promising early results, the delivery and therapeutic efficacy of the majority of NPs are still quite limited. This is mainly attributed to the limitation of currently available tumor models to test these NPs and systematically study the effects of complex transport and pathophysiological barriers around the tumors. In this study, thus, we developed a new in vitro tumor model to recapitulate the tumor microenvironment determining the transport around tumors. This model, named tumor-microenvironment-on-chip (T-MOC), consists of 3-dimensional microfluidic channels where tumor cells and endothelial cells are cultured within extracellular matrix under perfusion of interstitial fluid. Using this T-MOC platform, the transport of NPs and its variation due to tumor microenvironmental parameters have been studied including cut-off pore size, interstitial fluid pressure, and tumor tissue microstructure. The results suggest that T-MOC is capable of simulating the complex transport around the tumor, and providing detailed information about NP transport behavior. This finding confirms that NPs should be designed considering their dynamic interactions with tumor microenvironment. PMID:25194778

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.

Medicine Delivery Device with Integrated Sterilization and Detection

NASA Technical Reports Server (NTRS)

Shearn, Michael J.; Greer, Harold F.; Manohara, Harish

2013-01-01

Sterile delivery devices can be created by integrating a medicine delivery instrument with surfaces that are coated with germicidal and anti-fouling material. This requires that a large-surface-area template be developed within a constrained volume to ensure good contact between the delivered medicine and the germicidal material. Both of these can be integrated using JPL-developed silicon nanotip or cryo-etch black silicon technologies with atomic layer deposition (ALD) coating of specific germicidal layers. The application of semiconductor processing techniques and technologies to the problems of fluid manipulation and delivery has enabled the integration of chemical, electrical, and mechanical manipulation of samples all within a single microfluidic device. This approach has been successfully applied at JPL to the automated processing, detection, and analysis of minute quantities (parts per trillion level) of biomaterials to develop instruments for in situ exploration or extraterrestrial bodies. The same nanofabrication techniques that are used to produce a microfluidics device are also capable of synthesizing extremely high-surface-area templates in precise locations, and coating those surfaces with conformal films to manipulate their surface properties. This methodology has been successfully applied at JPL to produce patterned and coated silicon nanotips (also known as black silicon) to manipulate the hydrophilicity of surfaces to direct the spreading of fluids in microdevices. JPL's ALD technique is an ideal method to produce the highly conformal coatings required for this type of application. Certain materials, such as TiO2, have germicidal and anti-fouling properties when they are illuminated with UV light. The proposed delivery device contacts medicine with this high-surface-area black silicon surface coated with a thin-film germicidal deposited conformally with ALD. The coating can also be illuminated with ultraviolet light for the purpose of sterilization or identification of the medicine itself. This constrained volume that is located immediately prior to delivery into a patient, ensures that the medicine delivery device is inherently sterile. An additional benefit to integrating a high-surface-area template within the fluid channel of a medicine delivery device is that one can envision a number of different functional coatings that could facilitate the capture and analysis of either microbial contaminants or the medicine itself. For example, one could attach antibodies or some other binding agent with a specific affinity to the silicon nanotip template. Once a target molecule or microbe is bound to the high-surface- area template, one could use an optical analytical technique such as fluorescence or adsorption to determine the identity and potentially the concentration of the species of interest. By illuminating the bound species from the back, it may also be possible to probe only the molecules with an evanescent wave, making detection of the species from the front side of the device much simpler.

Vaginal Lactoferrin Modulates PGE2, MMP-9, MMP-2, and TIMP-1 Amniotic Fluid Concentrations

PubMed Central

Maritati, Martina; Gonelli, Arianna; Greco, Pantaleo

2016-01-01

Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs) imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF), an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n = 57) or treated with LF 4 hours before amniocentesis (n = 54). Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p < 0.01, p < 0.005, and p < 0.001, resp.). Conversely, active MMP-2 (p < 0.0001) and MMP-2/TIMP-2 molar ratio (p < 0.001) were increased, whilst TIMP-2 was unchanged. Our data suggest that LF administration is able to modulate the inflammatory response following amniocentesis, which may counteract cytokine and prostanoid imbalance that leads to abortion. This trial is registered with Clinical Trial number NCT02695563. PMID:27872513

Variability in Nose-to-Lung Aerosol Delivery

PubMed Central

Walenga, Ross L; Tian, Geng; Hindle, Michael; Yelverton, Joshua; Dodson, Kelley; Longest, P. Worth

2014-01-01

Nasal delivery of lung targeted pharmaceutical aerosols is ideal for drugs that need to be administered during high flow nasal cannula (HFNC) gas delivery, but based on previous studies losses and variability through both the delivery system and nasal cavity are expected to be high. The objective of this study was to assess the variability in aerosol delivery through the nose to the lungs with a nasal cannula interface for conventional and excipient enhanced growth (EEG) delivery techniques. A database of nasal cavity computed tomography (CT) scans was collected and analyzed, from which four models were selected to represent a wide range of adult anatomies, quantified based on the nasal surface area-to-volume ratio (SA/V). Computational fluid dynamics (CFD) methods were validated with existing in vitro data and used to predict aerosol delivery through a streamlined nasal cannula and the four nasal models at a steady state flow rate of 30 L/min. Aerosols considered were solid particles for EEG delivery (initial 0.9 μm and 1.5 μm aerodynamic diameters) and conventional droplets (5 μm) for a control case. Use of the EEG approach was found to reduce depositional losses in the nasal cavity by an order of magnitude and substantially reduce variability. Specifically, for aerosol deposition efficiency in the four geometries, the 95% confidence intervals (CI) for 0.9 and 5 μm aerosols were 2.3-3.1 and 15.5-66.3%, respectively. Simulations showed that the use of EEG as opposed to conventional methods improved delivered dose of aerosols through the nasopharynx, expressed as penetration fraction (PF), by approximately a factor of four. Variability of PF, expressed by the coefficient of variation (CV), was reduced by a factor of four with EEG delivery compared with the control case. Penetration fraction correlated well with SA/V for larger aerosols, but smaller aerosols showed some dependence on nasopharyngeal exit hydraulic diameter. In conclusion, results indicated that the EEG technique not only improved lung aerosol delivery, but largely eliminated variability in both nasal depositional loss and lung PF in a newly developed set of nasal airway models. PMID:25308992

Lecithin/TPGS-based spray-dried self-microemulsifying drug delivery systems: In vitro pulmonary deposition and cytotoxicity.

PubMed

Ishak, Rania A H; Osman, Rihab

2015-05-15

The aim of the present work was to develop a new solid self-microemulsifying drug delivery system (SMEDDS) for the pulmonary delivery of the poorly water-soluble anti-cancer drug atorvastatin (AVT). Microemulsion (ME) was first developed using isopropyl myristate (IPM), a combination of 2 biocompatible surfactants: lecithin/d-α-tocopheryl polyethylene glycol succinate (TPGS) and ethanol as co-surfactant. Two types of lecithin with different phosphatidylcholine (PC) contents were compared. Phase diagram, physico-chemical characterization and stability studies were used to investigate ME region. Solid SMEDDS were then prepared by spray-drying the selected ME using a combination of carriers composed of sugars, leucine as dispersibility enhancer with or without polyethylene glycol (PEG) 6000. Yield, flow properties, particle size and in vitro pulmonary deposition were used to characterize the spray-dried powders. Reconstituted MEs were characterized in terms of morphology, particle size and size distribution. In vitro cytotoxicity study was undertaken on lung cancer cell line for the selected MEs and SD-SMEDDS formulae. Results showed that the most satisfactory MEs properties were obtained with 1:3 lecithin/TPGS, 1:1 lecithin/oil and 1:1 surfactant/co-surfactant ratios. A larger ME area was obtained with lecithin containing 100% PC compared to the less expensive lecithin containing 20% PC. By manipulating spray drying parameters, carrier composition and ratio of ME lipids to carrier, microparticles with more than 70% of respirable fraction could be prepared. The ME was efficiently recovered in simulated lung fluid even after removal of alcohol. The concurrent delivery of AVT with TPGS in solid SMEDDS greatly enhanced the cytotoxic activity on lung cancer cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Temperature Control in a Franz Diffusion Cell Skin Sonoporation Setup

NASA Astrophysics Data System (ADS)

Robertson, Jeremy; Becker, Sid

2017-11-01

In vitro experimental studies that investigate ultrasound enhanced transdermal drug delivery employ Franz diffusion cells. Because of absorption, the temperature of the coupling fluid often increases drastically during the ultrasound application. The current methodologies for controlling the coupling fluid temperature require either replacement of the coupling fluid during the experiment or the application of a time consuming duty cycle. This paper introduces a novel method for temperature control that allows for a wide variety of coupling fluid temperatures to be maintained. This method employs a peristaltic pump to circulate the coupling fluid through a thermoelectric cooling device. This temperature control method allowed for an investigation into the role of coupling fluid temperature on the inertial cavitation that impacts the skin aperture (inertial cavitation is thought to be the main cause of ultrasound induced skin permeability increase). Both foil pitting and passive cavitation detection experiments indicated that effective inertial cavitation activity decreases with increasing coupling fluid temperature. This finding suggests that greater skin permeability enhancement can be achieved if a lower coupling fluid temperature is maintained during skin insonation.

An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake.

PubMed

Bode, Gerard H; Coué, Gregory; Freese, Christian; Pickl, Karin E; Sanchez-Purrà, Maria; Albaiges, Berta; Borrós, Salvador; van Winden, Ewoud C; Tziveleka, Leto-Aikaterini; Sideratou, Zili; Engbersen, Johan F J; Singh, Smriti; Albrecht, Krystyna; Groll, Jürgen; Möller, Martin; Pötgens, Andy J G; Schmitz, Christoph; Fröhlich, Eleonore; Grandfils, Christian; Sinner, Frank M; Kirkpatrick, C James; Steinbusch, Harry W M; Frank, Hans-Georg; Unger, Ronald E; Martinez-Martinez, Pilar

2017-04-01

Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. Copyright © 2016 Elsevier Inc. All rights reserved.

Developments in the Implementation of Acoustic Droplet Ejection for Protein Crystallography.

PubMed

Wu, Ping; Noland, Cameron; Ultsch, Mark; Edwards, Bonnie; Harris, David; Mayer, Robert; Harris, Seth F

2016-02-01

Acoustic droplet ejection (ADE) enables crystallization experiments at the low-nanoliter scale, resulting in rapid vapor diffusion equilibration dynamics and efficient reagent usage in the empirical discovery of structure-enabling protein crystallization conditions. We extend our validation of this technology applied to the diverse physicochemical property space of aqueous crystallization reagents where dynamic fluid analysis coupled to ADE aids in accurate and precise dispensations. Addition of crystallization seed stocks, chemical additives, or small-molecule ligands effectively modulates crystallization, and we here provide examples in optimization of crystal morphology and diffraction quality by the acoustic delivery of ultra-small volumes of these cofactors. Additional applications are discussed, including set up of in situ proteolysis and alternate geometries of crystallization that leverage the small scale afforded by acoustic delivery. Finally, we describe parameters of a system of automation in which the acoustic liquid handler is integrated with a robotic arm, plate centrifuge, peeler, sealer, and stacks, which allows unattended high-throughput crystallization experimentation. © 2015 Society for Laboratory Automation and Screening.

Human immune cell targeting of protein nanoparticles - caveospheres

NASA Astrophysics Data System (ADS)

Glass, Joshua J.; Yuen, Daniel; Rae, James; Johnston, Angus P. R.; Parton, Robert G.; Kent, Stephen J.; de Rose, Robert

2016-04-01

Nanotechnology has the power to transform vaccine and drug delivery through protection of payloads from both metabolism and off-target effects, while facilitating specific delivery of cargo to immune cells. However, evaluation of immune cell nanoparticle targeting is conventionally restricted to monocultured cell line models. We generated human caveolin-1 nanoparticles, termed caveospheres, which were efficiently functionalized with monoclonal antibodies. Using this platform, we investigated CD4+ T cell and CD20+ B cell targeting within physiological mixtures of primary human blood immune cells using flow cytometry, imaging flow cytometry and confocal microscopy. Antibody-functionalization enhanced caveosphere binding to targeted immune cells (6.6 to 43.9-fold) within mixed populations and in the presence of protein-containing fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere internalization by non-phagocytic CD4+ T cells--an important therapeutic target for HIV treatment. This efficient and flexible system of immune cell-targeted caveosphere nanoparticles holds promise for the development of advanced immunotherapeutics and vaccines.

Artificial dirt: microfluidic substrates for nematode neurobiology and behavior.

PubMed

Lockery, S R; Lawton, K J; Doll, J C; Faumont, S; Coulthard, S M; Thiele, T R; Chronis, N; McCormick, K E; Goodman, M B; Pruitt, B L

2008-06-01

With a nervous system of only 302 neurons, the free-living nematode Caenorhabditis elegans is a powerful experimental organism for neurobiology. However, the laboratory substrate commonly used in C. elegans research, a planar agarose surface, fails to reflect the complexity of this organism's natural environment, complicates stimulus delivery, and is incompatible with high-resolution optophysiology experiments. Here we present a new class of microfluidic devices for C. elegans neurobiology and behavior: agarose-free, micron-scale chambers and channels that allow the animals to crawl as they would on agarose. One such device mimics a moist soil matrix and facilitates rapid delivery of fluid-borne stimuli. A second device consists of sinusoidal channels that can be used to regulate the waveform and trajectory of crawling worms. Both devices are thin and transparent, rendering them compatible with high-resolution microscope objectives for neuronal imaging and optical recording. Together, the new devices are likely to accelerate studies of the neuronal basis of behavior in C. elegans.

Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors.

PubMed

Sheybani, Roya; Cobo, Angelica; Meng, Ellis

2015-08-01

We present a fully integrated implantable electrolysis-based micropump with incorporated EI dosing sensors. Wireless powering and data telemetry (through amplitude and frequency modulation) were utilized to achieve variable flow control and a bi-directional data link with the sensors. Wireless infusion rate control (0.14-1.04 μL/min) and dose sensing (bolus resolution of 0.55-2 μL) were each calibrated separately with the final circuit architecture and then simultaneous wireless flow control and dose sensing were demonstrated. Recombination detection using the dosing system, as well as, effects of coil separation distance and misalignment in wireless power and data transfer were studied. A custom-made normally closed spring-loaded ball check valve was designed and incorporated at the reservoir outlet to prevent backflow of fluids as a result of the reverse pressure gradient caused by recombination of electrolysis gases. Successful delivery, infusion rate control, and dose sensing were achieved in simulated brain tissue.

Periodontal disease and intra-amniotic complications in women with preterm prelabor rupture of membranes.

PubMed

Radochova, Vladimira; Kacerovska Musilova, Ivana; Stepan, Martin; Vescicik, Peter; Slezak, Radovan; Jacobsson, Bo; Kacerovsky, Marian

2017-08-04

Periodontal disease is frequently suggested as a possible causal factor for preterm delivery. The link between periodontal disease and preterm delivery is a possible translocation of periopathogenic bacteria to the placenta and amniotic fluid as well as a systemic response to this chronic inflammatory disease. However, there is a lack of information on whether there is an association between clinical periodontal status in women with preterm prelabor rupture of membranes (PPROM) and the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI). Therefore, the main aim of this study was to evaluate the incidence and severity of periodontal disease in women with PPROM. The secondary aim was to characterize an association between periodontal status and the presence of intra-amniotic PPROM complications (MIAC and/or IAI). Seventy-eight women with PPROM at gestational ages between 24 + 0 and 36 + 6 weeks were included in this study. The samples of amniotic fluid were obtained at admission via transabdominal amniocentesis, and amniotic fluid interleukin (IL)-6 concentrations were determined using a point-of-care test. All women had a full-mouth recording to determine the periodontal and oral hygiene status. Probing pocket depth and clinical attachment loss were measured at four sites on each fully erupted tooth. In total, 45% (35/78) of women with PPROM had periodontal disease. Mild, moderate, and severe periodontal disease was present in 19% (15/78), 19% (15/78), and 6% (5/78) of women, respectively. The presence of MIAC and IAI was found in 28% (22/78) and 26% (20/78) of women, respectively. Periopathogenic bacteria (2 × Streptococcus intermedius and 1 × Fusobacterium nucleatum) was found in the amniotic fluid of 4% (3/78) of women. There were no differences in periodontal status between women with MIAC and/or IAI and women without these intra-amniotic complications. The presence of MIAC and IAI was not related to the periodontal status of women with PPROM.

Bio-microfluidics: biomaterials and biomimetic designs.

PubMed

Domachuk, Peter; Tsioris, Konstantinos; Omenetto, Fiorenzo G; Kaplan, David L

2010-01-12

Bio-microfluidics applies biomaterials and biologically inspired structural designs (biomimetics) to microfluidic devices. Microfluidics, the techniques for constraining fluids on the micrometer and sub-micrometer scale, offer applications ranging from lab-on-a-chip to optofluidics. Despite this wealth of applications, the design of typical microfluidic devices imparts relatively simple, laminar behavior on fluids and is realized using materials and techniques from silicon planar fabrication. On the other hand, highly complex microfluidic behavior is commonplace in nature, where fluids with nonlinear rheology flow through chaotic vasculature composed from a range of biopolymers. In this Review, the current state of bio-microfluidic materials, designs and applications are examined. Biopolymers enable bio-microfluidic devices with versatile functionalization chemistries, flexibility in fabrication, and biocompatibility in vitro and in vivo. Polymeric materials such as alginate, collagen, chitosan, and silk are being explored as bulk and film materials for bio-microfluidics. Hydrogels offer options for mechanically functional devices for microfluidic systems such as self-regulating valves, microlens arrays and drug release systems, vital for integrated bio-microfluidic devices. These devices including growth factor gradients to study cell responses, blood analysis, biomimetic capillary designs, and blood vessel tissue culture systems, as some recent examples of inroads in the field that should lead the way in a new generation of microfluidic devices for bio-related needs and applications. Perhaps one of the most intriguing directions for the future will be fully implantable microfluidic devices that will also integrate with existing vasculature and slowly degrade to fully recapitulate native tissue structure and function, yet serve critical interim functions, such as tissue maintenance, drug release, mechanical support, and cell delivery.

Simultaneous use of intrapartum fetal pulse oximetry and amnioinfusion in meconium stained amniotic fluid.

PubMed

Halvax, László; Szabó, István; Vizer, Miklós; Csermely, Tamás; Ertl, Tibor

2002-09-10

Fetal pulse oximetry is a minimally invasive, simple technique which continuously helps to reflect in utero well-being. The presence of meconium in the amniotic fluid may be a clinical sign of fetal hypoxaemia. Amnioinfusion has a beneficial effect on the incidence of meconium aspiration syndrome (MAS), and the presence of meconium below the level of the vocal cords. We studied the impact of amnioinfusion combined with fetal pulse oximetry on the incidence of meconium aspiration syndrome and operative delivery. The retrospective analysis revealed that the presence of meconium below the level of vocal cords was significantly reduced. The frequency of cesarean section is decreased, however, it did not reach statistical significance. Fetal pulse oximetry may be used in combination with amnioinfusion and cardiotocography (CTG) to reduce the risk of meconium aspiration syndrome and the number of instrumental deliveries and improve perinatal outcome. Copyright 2002 Elsevier Science Ireland Ltd.

Eukaryote-Made Thermostable DNA Polymerase Enables Rapid PCR-Based Detection of Mycoplasma, Ureaplasma and Other Bacteria in the Amniotic Fluid of Preterm Labor Cases.

PubMed

Ueno, Tomohiro; Niimi, Hideki; Yoneda, Noriko; Yoneda, Satoshi; Mori, Masashi; Tabata, Homare; Minami, Hiroshi; Saito, Shigeru; Kitajima, Isao

2015-01-01

Intra-amniotic infection has long been recognized as the leading cause of preterm delivery. Microbial culture is the gold standard for the detection of intra-amniotic infection, but several days are required, and many bacterial species in the amniotic fluid are difficult to cultivate. We developed a novel nested-PCR-based assay for detecting Mycoplasma, Ureaplasma, other bacteria and fungi in amniotic fluid samples within three hours of sample collection. To detect prokaryotes, eukaryote-made thermostable DNA polymerase, which is free from bacterial DNA contamination, is used in combination with bacterial universal primers. In contrast, to detect eukaryotes, conventional bacterially-made thermostable DNA polymerase is used in combination with fungal universal primers. To assess the validity of the PCR assay, we compared the PCR and conventional culture results using 300 amniotic fluid samples. Based on the detection level (positive and negative), 93.3% (280/300) of Mycoplasma, 94.3% (283/300) of Ureaplasma, 89.3% (268/300) of other bacteria and 99.7% (299/300) of fungi matched the culture results. Meanwhile, concerning the detection of bacteria other than Mycoplasma and Ureaplasma, 228 samples were negative according to the PCR method, 98.2% (224/228) of which were also negative based on the culture method. Employing the devised primer sets, mixed amniotic fluid infections of Mycoplasma, Ureaplasma and/or other bacteria could be clearly distinguished. In addition, we also attempted to compare the relative abundance in 28 amniotic fluid samples with mixed infection, and judged dominance by comparing the Ct values of quantitative real-time PCR. We developed a novel PCR assay for the rapid detection of Mycoplasma, Ureaplasma, other bacteria and fungi in amniotic fluid samples. This assay can also be applied to accurately diagnose the absence of bacteria in samples. We believe that this assay will positively contribute to the treatment of intra-amniotic infection and the prevention of preterm delivery.

Eukaryote-Made Thermostable DNA Polymerase Enables Rapid PCR-Based Detection of Mycoplasma, Ureaplasma and Other Bacteria in the Amniotic Fluid of Preterm Labor Cases

PubMed Central

Yoneda, Noriko; Yoneda, Satoshi; Mori, Masashi; Tabata, Homare; Minami, Hiroshi; Saito, Shigeru; Kitajima, Isao

2015-01-01

Background Intra-amniotic infection has long been recognized as the leading cause of preterm delivery. Microbial culture is the gold standard for the detection of intra-amniotic infection, but several days are required, and many bacterial species in the amniotic fluid are difficult to cultivate. Methods We developed a novel nested-PCR-based assay for detecting Mycoplasma, Ureaplasma, other bacteria and fungi in amniotic fluid samples within three hours of sample collection. To detect prokaryotes, eukaryote-made thermostable DNA polymerase, which is free from bacterial DNA contamination, is used in combination with bacterial universal primers. In contrast, to detect eukaryotes, conventional bacterially-made thermostable DNA polymerase is used in combination with fungal universal primers. To assess the validity of the PCR assay, we compared the PCR and conventional culture results using 300 amniotic fluid samples. Results Based on the detection level (positive and negative), 93.3% (280/300) of Mycoplasma, 94.3% (283/300) of Ureaplasma, 89.3% (268/300) of other bacteria and 99.7% (299/300) of fungi matched the culture results. Meanwhile, concerning the detection of bacteria other than Mycoplasma and Ureaplasma, 228 samples were negative according to the PCR method, 98.2% (224/228) of which were also negative based on the culture method. Employing the devised primer sets, mixed amniotic fluid infections of Mycoplasma, Ureaplasma and/or other bacteria could be clearly distinguished. In addition, we also attempted to compare the relative abundance in 28 amniotic fluid samples with mixed infection, and judged dominance by comparing the Ct values of quantitative real-time PCR. Conclusions We developed a novel PCR assay for the rapid detection of Mycoplasma, Ureaplasma, other bacteria and fungi in amniotic fluid samples. This assay can also be applied to accurately diagnose the absence of bacteria in samples. We believe that this assay will positively contribute to the treatment of intra-amniotic infection and the prevention of preterm delivery. PMID:26042418

Recovery of Drug Delivery Nanoparticles from Human Plasma Using an Electrokinetic Platform Technology.

PubMed

Ibsen, Stuart; Sonnenberg, Avery; Schutt, Carolyn; Mukthavaram, Rajesh; Yeh, Yasan; Ortac, Inanc; Manouchehri, Sareh; Kesari, Santosh; Esener, Sadik; Heller, Michael J

2015-10-01

The effect of complex biological fluids on the surface and structure of nanoparticles is a rapidly expanding field of study. One of the challenges holding back this research is the difficulty of recovering therapeutic nanoparticles from biological samples due to their small size, low density, and stealth surface coatings. Here, the first demonstration of the recovery and analysis of drug delivery nanoparticles from undiluted human plasma samples through the use of a new electrokinetic platform technology is presented. The particles are recovered from plasma through a dielectrophoresis separation force that is created by innate differences in the dielectric properties between the unaltered nanoparticles and the surrounding plasma. It is shown that this can be applied to a wide range of drug delivery nanoparticles of different morphologies and materials, including low-density nanoliposomes. These recovered particles can then be analyzed using different methods including scanning electron microscopy to monitor surface and structural changes that result from plasma exposure. This new recovery technique can be broadly applied to the recovery of nanoparticles from high conductance fluids in a wide range of applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Concept and treatment of hydrocephalus in the Greco-Roman and early Arabic medicine.

PubMed

Grunert, P; Charalampaki, P; Ayyad, A

2007-10-01

In the ancient medical literature hydrocephalus was not often described although its existence and symptomatology were well known. Most detailed descriptions of hydrocephalus including the surgical treatment are extant in the encyclopaedic works on medicine of the physicians Oreibasios and Aetios from Amida from the 4th and 6th centuries AD, respectively. Because of their broad scientific interests, this type of physicians, typical for the late Roman empire, were known as philosophy-physicians (iota alpha tau rho o sigma o phi iota sigma tau alpha iota). They defined hydrocephalus in contrast to our present understanding as a fluid collection excluding abscesses visible as a bulging tumour localised either outside or inside the skull of an infant. They classified the hydrocephalus similar as stated first by Galen in the 2nd century AD in four types corresponding to the assumed anatomic localisation of the fluid collection: 1st Type between the skin and the pericranium corresponding to the subgaleal haematoma or caput succedaneum of the newborn in our terminology, 2nd Type between the pericranium and the skull corresponding to the cephal haematoma after delivery, 3rd Type between skull and the meninges with increased head circumference, bone sutures being increasingly driven apart corresponding most likely to the hydrocephalus in our understanding, and 4th Type between the menings and the brain characterised by severe neurological deficit with lethal prognosis corresponding probably to all pathologies which were accompanied by an excessive increase of the intracranial pressure with a bulging fontanel. Due to the lack of autopsies in ancient times, the hydrocephalus was never linked to the pathology of the ventricles. All forms of hydrocephalus were believed to be caused by improper handling of the head by the midwife during delivery. Only the extracranial fluid collections, but not hydrocephalus in our sense, were considered to be suitable for surgical treatment. The surgery consisted in one or more incisions and evacuation of the fluid. The wound was not closed but let open for three days. Thereafter plasters or sutures closed the incisions. The surgical technique goes back probably to Antyllos a surgeon from the 3rd century AD whose considerations were cited in the work of Oreibasios. The early Arabic physicians took over the surgical indications, the operative technique and modified the Greek concept of hydrocephalus. Avicenna separated the traumatic haematomas outside the skull from the term hydrocephalus. However Avicenna, as all previous authors, had not linked hydrocephalus with the ventricular system. The autopsy of a child with an exorbitant hydrocephalus performed by the anatomist Vesalius in the 16th century revealed as a single pathology an extremely dilative ventricular system filled with water-like fluid which made it necessary to change completely the ancient concept of hydrocephalus.

Fluids and Combustion Facility: Combustion Integrated Rack Modal Model Correlation

NASA Technical Reports Server (NTRS)

McNelis, Mark E.; Suarez, Vicente J.; Sullivan, Timothy L.; Otten, Kim D.; Akers, James C.

2005-01-01

The Fluids and Combustion Facility (FCF) is a modular, multi-user, two-rack facility dedicated to combustion and fluids science in the US Laboratory Destiny on the International Space Station. FCF is a permanent facility that is capable of accommodating up to ten combustion and fluid science investigations per year. FCF research in combustion and fluid science supports NASA's Exploration of Space Initiative for on-orbit fire suppression, fire safety, and space system fluids management. The Combustion Integrated Rack (CIR) is one of two racks in the FCF. The CIR major structural elements include the International Standard Payload Rack (ISPR), Experiment Assembly (optics bench and combustion chamber), Air Thermal Control Unit (ATCU), Rack Door, and Lower Structure Assembly (Input/Output Processor and Electrical Power Control Unit). The load path through the rack structure is outlined. The CIR modal survey was conducted to validate the load path predicted by the CIR finite element model (FEM). The modal survey is done by experimentally measuring the CIR frequencies and mode shapes. The CIR model was test correlated by updating the model to represent the test mode shapes. The correlated CIR model delivery is required by NASA JSC at Launch-10.5 months. The test correlated CIR flight FEM is analytically integrated into the Shuttle for a coupled loads analysis of the launch configuration. The analysis frequency range of interest is 0-50 Hz. A coupled loads analysis is the analytical integration of the Shuttle with its cargo element, the Mini Payload Logistics Module (MPLM), in the Shuttle cargo bay. For each Shuttle launch configuration, a verification coupled loads analysis is performed to determine the loads in the cargo bay as part of the structural certification process.

Absorption sites of orally administered drugs in the small intestine.

PubMed

Murakami, Teruo

2017-12-01

In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

Alginate-Based Composite Sponges as Gastroretentive Carriers for Curcumin-Loaded Self-Microemulsifying Drug Delivery Systems

PubMed Central

Petchsomrit, Arpa; Sermkaew, Namfa; Wiwattanapatapee, Ruedeekorn

2017-01-01

Alginate-based composite sponges were developed as carriers to prolong the gastric retention time and controlled release of curcumin-loaded self-microemulsifying drug delivery systems (Cur-SMEDDS). Liquid Cur-SMEDDS was incorporated into a solution made up of a mixture of polymers and converted into a solid form by freeze-drying. The ratio of alginate as the main polymer, adsorbent (colloidal silicon dioxide), and additional polymers—sodium carboxymethyl cellulose (SCMC), hydroxypropyl methylcellulose (HPMC)—was varied systematically to adjust the drug loading and entrapment efficiency, sponge buoyancy, and the release profile of Cur-SMEDDS. The optimum composite sponge was fabricated from a 4% alginate and 2% HPMC mixed solution. It immediately floated on simulated gastric fluid (SGF, pH 1.2) and remained buoyant over an 8 h period. The formulation exhibited an emulsion droplet size of approximately 30 nm and provided sustained release of Cur-SMEDDS in SGF, reaching 71% within 8 h compared with only 10% release from curcumin powder. This study demonstrates the potential of alginate-based composite sponges combined with self-microemulsifying formulations for gastroretention applications involving poorly soluble compounds. PMID:28294964

Comparative studies on structural properties and antimicrobial potential of spinel ferrite nanoparticles synthesized using various methods

NASA Astrophysics Data System (ADS)

Baraliya, Jagdish D.; Rakhashiya, Purvi M.; Patel, Pooja P.; Thaker, Vrinda S.; Joshi, Hiren H.

2017-05-01

In this study, novel multifunctional magnetic iron-based nanoparticles (CoFe2O4) coated with silica, silica-DEG (diethylene glycol), PEG (polyethylene glycol) were synthesized using Auto Combustion Method (ACM), Co-precipitation Method (COPM), Citrate Precursor Method (CPM), Flash Combustion Method (FCM). These spinel ferrite nanoparticles also contain very high antibacterial properties to fulfill the requirements of a drug delivery system so that the antibiotic concentration could be minimized. A potential delivery system could be based on a ferromagnetic fluid. The effects of various preparation methods on the physical properties of the nanoparticles were examined. The nanoparticles were also tested against four human pathogenic bacteria (Gram negative E.coli, P. aeruginosa, Gram positive S. aureus, S. pyogenus) and two fungi (C. albicans, A.niger). It was revealed that a nanoparticle has strong antibacterial activity as compared to antifungal. Further, Gram positive bacteria are more affected than Gram negative bacteria. It was also clear that different methods of coating have great influence on the antimicrobial properties. It was observed that these nanoparticles have significantly different but potentially very high antimicrobial activities against the tested organisms than found elsewhere by other nanoparticles on the same organisms.

A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses.

PubMed

Klier, John; Fuchs, Sebastian; May, Anna; Schillinger, Ulrike; Plank, Christian; Winter, Gerhard; Coester, Conrad; Gehlen, Heidrun

2012-06-01

In the recent years, nanotechnology has boosted the development of potential drug delivery systems and material engineering on nanoscale basis in order to increase drug specificity and reduce side effects. A potential delivery system for immunostimulating agents such as cytosine-phosphate-guanine-oligodeoxynucleotides (CpG-ODN) needs to be developed to maximize the efficacy of immunotherapy against hypersensitivity. In this study, an aerosol formulation of biodegradable, biocompatible and nontoxic gelatin nanoparticle-bound CpG-ODN 2216 was used to treat equine recurrent airway obstruction in a clinical study. Bronchoalveolar lavage fluid was obtained from healthy and allergic horses to quantify Th1/Th2 cytokine levels before and after inhalation regimen. Full clinical examinations were performed to evaluate the therapeutic potential of this nebulized gelatin nanoparticle-based CpG formulation. Most remarkable was that regulatory anti-inflammatory and anti-allergic cytokine IL-10 expression was significantly triggered by five consecutive inhalations. Thorough assessment of clinical parameters following nanoparticle treatment indicated a partial remission of the allergic condition. Thus this study, for the first time, showed effectiveness of colloidal nanocarrier-mediated immunotherapy in food-producing animals with potential future applicability to other species including humans.

Bio-based topical system for enhanced salicylic acid delivery: preparation and performance of gels.

PubMed

Langasco, Rita; Spada, Gianpiera; Tanriverdi, Sakine Tuncay; Rassu, Giovanna; Giunchedi, Paolo; Özer, Özgen; Gavini, Elisabetta

2016-08-01

New salicylic acid (SA)-loaded gels were developed using excipients made from renewable materials, and our goal was to improve drug permeation in the topical treatment of acne vulgaris. We studied the preparation parameters to obtain suitable gel formulations. Only naturally occurring polymers were used as gelling agents. Two hydrogels and three lipogels were selected and characterized in terms of drug loading, pH, viability cells, rheology, mechanical properties and in vitro permeation; these hydrogels and lipogels were compared with the traditional ointment. We also evaluated skin parameters before and after gel application. The formulations that we studied are non-Newtonian fluids; they have high drug loading and suitable mechanical properties. Lipogels exhibit a slower and more linear in vitro permeation profile compared with hydrogels. The different vehicles that we used affected drug permeation and improve patient compliance. Cytotoxicity studies suggest that all of the formulations are non-toxic. Lipogels demonstrate appropriate technological features and improved performance compared with the traditional ointment with regard to their composition. Lipogels may represent a new bio-based topical system for SA delivery. The use of 'green' excipients leads to 'skin-friendly' formulations that are able to satisfy environmental safety. © 2016 Royal Pharmaceutical Society.

Supercritical fluid particle design for poorly water-soluble drugs (review).

PubMed

Sun, Yongda

2014-01-01

Supercritical fluid particle design (SCF PD) offers a number of routes to improve solubility and dissolution rate for enhancing the bioavailability of poorly water-soluble drugs, which can be adopted through an in-depth knowledge of SCF PD processes and the molecular properties of active pharmaceutical ingredients (API) and drug delivery system (DDS). Combining with research experiences in our laboratory, this review focuses on the most recent development of different routes (nano-micron particles, polymorphic particles, composite particles and bio-drug particles) to improve solubility and dissolution rate of poorly water-soluble drugs, covering the fundamental concept of SCF and the principle of SCF PD processes which are typically used to control particle size, shape, morphology and particle form and hence enable notable improvement in the dissolution rate of the poorly water-soluble drugs. The progress of the industrialization of SCF PD processes in pharmaceutical manufacturing environment with scaled-up plant under current good manufacturing process (GMP) specification is also considered in this review.

Continuous subcutaneous delivery of medications for home care palliative patients-using an infusion set or a pump?

PubMed

Menahem, Sasson; Shvartzman, Pesach

2010-09-01

The purpose of this study was to evaluate safety, feasibility, and efficacy of continuous drug delivery by the subcutaneous route through a solution bag connected to an infusion set compared with an infusion pump in a home palliative care setting. Patients in need of continuous subcutaneous medication delivery for pain control, nausea, and/or vomiting were recruited. The study was designed as a double-blind, crossover study. The patient was connected to two parallel subcutaneous lines running simultaneously, connected together to a line entering the subcutaneous tissue. One line is connected to an infusion set and the other to a pump. The infusion set included a 500-cc solution bag connected to a 1.5-m plastic tube containing a drip chamber controlled by a roller clamp that is gravity driven without hyaluronidase. Active medications were randomly assigned to start in either administration method and switched after 24 h. An independent research assistant evaluated symptom control and side effects at baseline and every 24 h for 2 days using a structured questionnaire. Another independent research assistant connected the lines after adding medications and evaluated technical and clinical failures. Twenty-seven patients were recruited, and of them, 18 completed the study. Incidents in fluid administration were more common through the infusion set (18 times) compared to the pump (only twice). On the other hand, no clinical significant change was noted in the average symptom levels and side effects when medications were given through the infusion set versus the pump. No local edema or irritation was observed in either way of administration. In a home palliative care setting with a medical staff on call for 24 h, using medications for symptom control can be considered to be infused to a fluid solution bag through an infusion set instead of using a syringe driver or a pump when there is a responsible caregiver to follow up on the fluid. Subcutaneous constant drug delivery through a pump is more accurate.

Experimental and numerical models of three-dimensional gravity-driven flow of shear-thinning polymer solutions used in vaginal delivery of microbicides.

PubMed

Kheyfets, Vitaly O; Kieweg, Sarah L

2013-06-01

HIV/AIDS is a growing global pandemic. A microbicide is a formulation of a pharmaceutical agent suspended in a delivery vehicle, and can be used by women to protect themselves against HIV infection during intercourse. We have developed a three-dimensional (3D) computational model of a shear-thinning power-law fluid spreading under the influence of gravity to represent the distribution of a microbicide gel over the vaginal epithelium. This model, accompanied by a new experimental methodology, is a step in developing a tool for optimizing a delivery vehicle's structure/function relationship for clinical application. We compare our model with experiments in order to identify critical considerations for simulating 3D free-surface flows of shear-thinning fluids. Here we found that neglecting lateral spreading, when modeling gravity-induced flow, resulted in up to 47% overestimation of the experimental axial spreading after 90 s. In contrast, the inclusion of lateral spreading in 3D computational models resulted in rms errors in axial spreading under 7%. In addition, the choice of the initial condition for shape in the numerical simulation influences the model's ability to describe early time spreading behavior. Finally, we present a parametric study and sensitivity analysis of the power-law parameters' influence on axial spreading, and to examine the impact of changing rheological properties as a result of dilution or formulation conditions. Both the shear-thinning index (n) and consistency (m) impacted the spreading length and deceleration of the moving front. The sensitivity analysis showed that gels with midrange m and n values (for the ranges in this study) would be most sensitive (over 8% changes in spreading length) to 10% changes (e.g., from dilution) in both rheological properties. This work is applicable to many industrial and geophysical thin-film flow applications of non-Newtonian fluids; in addition to biological applications in microbicide drug delivery.

Experimental and Numerical Models of Three-Dimensional Gravity-Driven Flow of Shear-Thinning Polymer Solutions Used in Vaginal Delivery of Microbicides

PubMed Central

Kheyfets, Vitaly O.; Kieweg, Sarah L.

2013-01-01

HIV/AIDS is a growing global pandemic. A microbicide is a formulation of a pharmaceutical agent suspended in a delivery vehicle, and can be used by women to protect themselves against HIV infection during intercourse. We have developed a three-dimensional (3D) computational model of a shear-thinning power-law fluid spreading under the influence of gravity to represent the distribution of a microbicide gel over the vaginal epithelium. This model, accompanied by a new experimental methodology, is a step in developing a tool for optimizing a delivery vehicle's structure/function relationship for clinical application. We compare our model with experiments in order to identify critical considerations for simulating 3D free-surface flows of shear-thinning fluids. Here we found that neglecting lateral spreading, when modeling gravity-induced flow, resulted in up to 47% overestimation of the experimental axial spreading after 90 s. In contrast, the inclusion of lateral spreading in 3D computational models resulted in rms errors in axial spreading under 7%. In addition, the choice of the initial condition for shape in the numerical simulation influences the model's ability to describe early time spreading behavior. Finally, we present a parametric study and sensitivity analysis of the power-law parameters' influence on axial spreading, and to examine the impact of changing rheological properties as a result of dilution or formulation conditions. Both the shear-thinning index (n) and consistency (m) impacted the spreading length and deceleration of the moving front. The sensitivity analysis showed that gels with midrange m and n values (for the ranges in this study) would be most sensitive (over 8% changes in spreading length) to 10% changes (e.g., from dilution) in both rheological properties. This work is applicable to many industrial and geophysical thin-film flow applications of non-Newtonian fluids; in addition to biological applications in microbicide drug delivery. PMID:23699721

Computer Simulations of the Tumor Vasculature: Applications to Interstitial Fluid Flow, Drug Delivery, and Oxygen Supply.

PubMed

Welter, Michael; Rieger, Heiko

2016-01-01

Tumor vasculature, the blood vessel network supplying a growing tumor with nutrients such as oxygen or glucose, is in many respects different from the hierarchically organized arterio-venous blood vessel network in normal tissues. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature. Integrative models, based on detailed experimental data and physical laws, implement, in silico, the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. This chapter provides an overview over the current status of computer simulations of vascular remodeling during tumor growth including interstitial fluid flow, drug delivery, and oxygen supply within the tumor. The model predictions are compared with experimental and clinical data and a number of longstanding physiological paradigms about tumor vasculature and intratumoral solute transport are critically scrutinized.

Management of acute overdose or withdrawal state in intrathecal baclofen therapy.

PubMed

Watve, S V; Sivan, M; Raza, W A; Jamil, F F

2012-02-01

Individuals who are treated with intrathecal Baclofen (ITB) pump delivery system for intractable spasticity can suffer from severe morbidity as a result of acute overdose or withdrawal of ITB, which can also be life threatening. Current literature has a number of single case studies with different approaches to the management in such states. The aim of this article is to consolidate available evidence and develop treatment pathways for acute ITB overdose and withdrawal states. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library databases using the keywords 'intrathecal', 'baclofen', 'withdrawal', 'overdose' to identify studies (published up to December 2010) that focused on presentation or treatment of acute overdose and withdrawal state in ITB therapy. Only original articles in English involving adult population were included. Initial search revealed 130 articles. After reading the abstract, 13 studies on ITB overdose and 23 studies on ITB withdrawal were deemed suitable for inclusion. All studies were either single-case studies or case series. Acute ITB overdose is managed with immediate cessation of baclofen delivery through the system, reducing the baclofen load by cerebrospinal fluid aspiration and by providing supportive treatment in an intensive care setting. There is no specific antidote for reversing overdose symptoms. Acute ITB withdrawal is managed by restoring the delivery of ITB, providing supportive care in an intensive care setting and using drugs like low dose propofol or benzodiazepines in selected cases. Early involvement of ITB physicians is strongly recommended.

Ordered cubic nanoporous silica support MCM-48 for delivery of poorly soluble drug indomethacin

NASA Astrophysics Data System (ADS)

Zeleňák, Vladimír; Halamová, Dáša; Almáši, Miroslav; Žid, Lukáš; Zeleňáková, Adriána; Kapusta, Ondrej

2018-06-01

Ordered MCM-48 nanoporous silica (SBET = 923(3) m2·g-1, VP = 0.63(2) cm3·g-1) with cubic Ia3d symmetry was used as a support for drug delivery of anti-inflammatory poorly soluble drug indomethacin. The delivery from parent, unmodified MCM-48, and 3-aminopropyl modified silica carrier was studied into the simulated body fluids with the pH = 2 and pH = 7.4. The studied samples were characterized by thermal analysis (TG/DTG-DTA), N2 adsorption/desorption, infrared spectroscopy (FT-IR), powder XRD, SEM, HRTEM methods, measurements of zeta potential (ζ) and dynamic light scattering (DLS). The determined content of indomethacin in pure MCM-48 was 21 wt.% and in the amine-modified silica MCM-48A-I the content was 45 wt.%. The release profile of the drug, in the time period up to 72 h, was monitored by TLC chromatographic method. It as shown, that by the modification of the surface, the drug release can be controlled. The slower release of indomethacin was observed from amino modified sample MCM-48A-I in the both types of studied simulated body fluids (slightly alkaline intravenous solution with pH = 7.4 and acidic gastric fluid with pH = 2), which was supported and explained by zeta potential and DLS measurements. The amount of the released indomethacin into the fluids with various pH was different. The maximum released amount of the drug was 97% for sample containing unmodified silica, MCM-48-I at pH = 7.4 and lowest released amount, 57%, for amine modified sample MCM-48A-I at pH = 2. To compare the indomethacin release profile four kinetic models were tested. Results showed, that that the drug release based on diffusion Higuchi model, mainly governs the release.

Enteric-coating of pulsatile-release HPC capsules prepared by injection molding.

PubMed

Macchi, E; Zema, L; Maroni, A; Gazzaniga, A; Felton, L A

2015-04-05

Capsular devices based on hydroxypropyl cellulose (Klucel® LF) intended for pulsatile release were prepared by injection molding (IM). In the present work, the possibility of exploiting such capsules for the development of colonic delivery systems based on a time-dependent approach was evaluated. For this purpose, it was necessary to demonstrate the ability of molded cores to undergo a coating process and that coated systems yield the desired performance (gastric resistance). Although no information was available on the coating of IM substrates, some issues relevant to that of commercially-available capsules are known. Thus, preliminary studies were conducted on molded disks for screening purposes prior to the spray-coating of HPC capsular cores with Eudragit® L 30 D 55. The ability of the polymeric suspension to wet the substrate, spread, start penetrating and initiate hydration/swelling, as well as to provide a gastroresistant barrier was demonstrated. The coating of prototype HPC capsules was carried out successfully, leading to coated systems with good technological properties and able to withstand the acidic medium with no need for sealing at the cap/body joint. Such systems maintained the original pulsatile release performance after dissolution of the enteric film in pH 6.8 fluid. Therefore, they appeared potentially suitable for the development of a colon delivery platform based on a time-dependent approach. Copyright © 2015 Elsevier B.V. All rights reserved.

PROMOTE Study: Safety of Osteopathic Manipulative Treatment During the Third Trimester by Labor and Delivery Outcomes.

PubMed

Hensel, Kendi L; Roane, Brandy M; Chaphekar, Anita Vikas; Smith-Barbaro, Peggy

2016-11-01

Few quality data exist on the safety of osteopathic manipulative treatment (OMT) during pregnancy. The Pregnancy Research on Osteopathic Manipulation Optimizing Treatment Effects (PROMOTE) study was a randomized controlled clinical trial that studied the application of an OMT protocol to manage pain and dysfunction in pregnant patients during their third trimester. To evaluate the safety of an OMT protocol applied during the third trimester of pregnancy by analyzing incidence of high-risk status and labor and delivery outcomes. In the PROMOTE study, 400 pregnant patients were randomly assigned to 1 of 3 study groups: usual care plus OMT (OMT), usual care plus placebo ultrasound treatment (PUT), or usual care only (UCO). The incidence of high-risk status of participants and outcomes of labor and delivery, including length of labor, fever in mother during labor, operative vaginal delivery, conversion to cesarean delivery, need for forceps or vacuum device, need for episiotomy, incidence of perineal laceration, meconium-stained amniotic fluid, and infants' Apgar scores, were analyzed. Data from 380 participants were studied. High-risk status was less likely to develop in participants who received OMT (95% CI, 0.16-0.91; P=.03). The OMT protocol also did not increase risk of precipitous labor, operative vaginal delivery, conversion to cesarean delivery, need for forceps or vacuum device, need for episiotomy, incidence of perineal laceration, or meconium-stained amniotic fluid when compared with participants in the other 2 groups (P>.05). Of all other maternal outcomes examined, no difference was reported among the 3 treatment groups with the exception of incidence of prolonged labor in the OMT group. Participants receiving OMT had longer durations of labor than participants in the other groups (P=.002). These results suggest that the OMT protocol given during the third trimester of pregnancy as applied in the PROMOTE study is safe with regard to labor and delivery outcomes. The increased duration in labor in the OMT group needs further study. (ClinicalTrials.gov number NCT00426244).

Fluid therapy and the hypovolemic microcirculation.

PubMed

Gruartmoner, G; Mesquida, J; Ince, Can

2015-08-01

In shock states, optimizing intravascular volume is crucial to promote an adequate oxygen delivery to the tissues. Our current practice in fluid management pivots on the Frank-Starling law of the heart, and the effects of fluids are measured according to the induced changes on stroke volume. The purpose of this review is to evaluate the boundaries of current macrohemodynamic approach to fluid administration, and to introduce the microcirculatory integration as a fundamental part of tissue perfusion monitoring. Macrocirculatory changes induced by volume expansion are not always coupled to proportional changes in microcirculatory perfusion. Loss of hemodynamic coherence limits the value of guiding fluid therapy according to macrohemodynamics, and highlights the importance of evaluating the ultimate target of volume administration, the microcirculation. Current approach to intravascular volume optimization is made from a macrohemodynamic perspective. However, several situations wherein macrocirculatory and microcirculatory coherence is lost have been described. Future clinical trials should explore the usefulness of integrating the microcirculatory evaluation in fluid optimization.

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.

Formulation and in vitro evaluation of Hydrodynamically balanced system for theophylline delivery.

PubMed

Nayak, Amit Kumar; Malakar, Jadupati

2011-06-01

The objective of the present study was to formulate hydrodynamically balanced systems (HBSs) of theophylline as single unit capsules. They were formulated by physical blending of theophylline with hydroxypropyl methyl cellulose, polyethylene oxide, polyvinyl pyrrolidone, ethyl cellulose, liquid paraffin, and lactose in different ratios. These theophylline HBS capsules were evaluated for weight uniformity, drug content uniformity, in vitro floating behavior and drug release in simulated gastric fluids (pH 1.2). All these formulated HBS capsules containing theophylline were floated well over 6 hours with no floating lag time, and also showed sustained in vitro drug release in simulated gastric fluid over 6 hours. The theophylline release from these capsules was more sustained with the addition of release modifiers (ethyl cellulose and liquid paraffin). The drug release pattern from these capsules was correlated well with first order model (F-1 to F-5) and Korsmeyer-Peppas model (F-6 and F-7) with the non-Fickian (anomalous) diffusion mechanism. These experimental results clearly indicated that these theophylline HBS capsules were able to remain buoyant in the gastric juice for longer period, which may improve oral bioavailability of theophylline.

Automated reagent-dispensing system for microfluidic cell biology assays.

PubMed

Ly, Jimmy; Masterman-Smith, Michael; Ramakrishnan, Ravichandran; Sun, Jing; Kokubun, Brent; van Dam, R Michael

2013-12-01

Microscale systems that enable measurements of oncological phenomena at the single-cell level have a great capacity to improve therapeutic strategies and diagnostics. Such measurements can reveal unprecedented insights into cellular heterogeneity and its implications into the progression and treatment of complicated cellular disease processes such as those found in cancer. We describe a novel fluid-delivery platform to interface with low-cost microfluidic chips containing arrays of microchambers. Using multiple pairs of needles to aspirate and dispense reagents, the platform enables automated coating of chambers, loading of cells, and treatment with growth media or other agents (e.g., drugs, fixatives, membrane permeabilizers, washes, stains, etc.). The chips can be quantitatively assayed using standard fluorescence-based immunocytochemistry, microscopy, and image analysis tools, to determine, for example, drug response based on differences in protein expression and/or activation of cellular targets on an individual-cell level. In general, automation of fluid and cell handling increases repeatability, eliminates human error, and enables increased throughput, especially for sophisticated, multistep assays such as multiparameter quantitative immunocytochemistry. We report the design of the automated platform and compare several aspects of its performance to manually-loaded microfluidic chips.

Transcleral delivery of triamcinolone acetonide and ranibizumab to retinal tissues using macroesis.

PubMed

Singh, Rishi P; Mathews, Michael Ellen; Kaufman, Michael; Riga, Alan

2010-02-01

To determine the feasibility of macroesis for the delivery of ranibizumab and triamcinolone acetonide via a transcleral route. Macroesis is a non-invasive method of drug delivery that uses alternating current (AC) to deliver drugs to target tissues. Two preclinical models of drug delivery were used for feasibility studies of delivering ranibizumab and triamcinolone acetonide to ocular tissues. In the first model, full-thickness sections of rabbit ocular tissue (conjunctiva to retina) were placed on an interdigitated electrode platform, and the drug was placed on the surface of the tissue. A non-uniform electrical field was applied to the ocular tissue, and electrical conductivity, a measurement of drug delivery, was monitored during the course of the experiment. In a second model, termed a 'simulated vitreous model,' the same full-thickness sections of rabbit ocular tissue were mounted below the electrode device, and the test compounds were placed on the electrodes. The fluid below the tissue, which simulated the vitreous cavity, was analysed using UV spectroscopy at the end of the study for the presence of drug. In the electrical conductivity studies, the electric characteristics of the tissue-drug system clearly showed movement of the drug through the tissue to the dielectric sensor based on changes in the electrical conductivity of the tissue sample with triamcinolone. No change in tissue conductivity was observed when no drug was placed. No heat generation occurred during the course of the study; nor was any gross tissue destruction noted. In the simulated vitreous model, studies using triamcinolone yielded concentrations ranging from 0.280 to 0.970 mg/ml, depending on the voltage, frequency and time applied. In as little as 6.7 min, clinically efficacious doses could be obtained in the preclinical system. Studies using ranibizumab yielded concentrations of 0.070-0.171 mg/ml, depending on the voltage, frequency, and time applied. In as little at 6.7 min, 92.8% throughput could be achieved. Successful delivery of ranibizumab and triamcinolone acetonide can be achieved with macroesis in preclinical studies.

Healing of partial thickness porcine skin wounds in a liquid environment.

PubMed

Breuing, K; Eriksson, E; Liu, P; Miller, D R

1992-01-01

This study employs a liquid-tight vinyl chamber for the topical fluid-phase treatment of experimental wounds in pigs. Continuous treatment with normal saline significantly reduced the early progression of tissue destruction in partial thickness burns. Uncovered burns formed a deep layer of necrosis (0.49 +/- 0.004 mm, mean +/- SD) although burn wounds covered with empty chambers demonstrated less necrosis (0.14 +/- 0.01 mm), fluid-treated wounds formed no eschar, and little tissue necrosis could be detected (less than 0.005 mm). Topical treatment with hypertonic dextran increased water flux across burn wounds by 0.24 ml/cm2/24 hr (mean, n = 95) over saline-treated wounds during the first 5 days after wounding. When partial thickness burn and excisional wounds were immersed in isotonic saline until healed, the daily efflux of water, protein, electrolytes, and glucose across the wound surface declined during healing to baseline values found in controls (saline-covered unwounded skin). The declining protein permeability was used as a reproducible, noninvasive, endogenous marker for the return of epithelial barrier function. Saline-treated excisional wounds healed within 8.6 +/- 0.6 days (mean +/- SD, n = 27) and burn wounds within 12.1 +/- 1.4 days (mean +/- SD, n = 15). Healing of fluid-treated wounds occurred without tissue maceration and showed less inflammation and less scar formation than healing of air exposed wounds (no attempt was made to compare rates of healing between air- and fluid-exposed wounds). We consider the fluid-filled chamber a potentially very useful diagnostic, monitoring, and delivery system for wound-healing research and for human wound therapy.

Engineering Sedimentary Geothermal Resources for Large-Scale Dispatchable Renewable Electricity

NASA Astrophysics Data System (ADS)

Bielicki, Jeffrey; Buscheck, Thomas; Chen, Mingjie; Sun, Yunwei; Hao, Yue; Saar, Martin; Randolph, Jimmy

2014-05-01

Mitigating climate change requires substantial penetration of renewable energy and economically viable options for CO2 capture and storage (CCS). We present an approach using CO2 and N2 in sedimentary basin geothermal resources that (1) generates baseload and dispatchable power, (2) efficiently stores large amounts of energy, and (3) enables seasonal storage of solar energy, all which (5) increase the value of CO2 and render CCS commercially viable. Unlike the variability of solar and wind resources, geothermal heat is a constant source of renewable energy. Using CO2 as a supplemental geothermal working fluid, in addition to brine, reduces the parasitic load necessary to recirculate fluids. Adding N2 is beneficial because it is cheaper, will not react with materials and subsurface formations, and enables bulk energy storage. The high coefficients of thermal expansion of CO2 and N2 (a) augment reservoir pressure, (b) generate artesian flow at the production wells, and (c) produce self-convecting thermosiphons that directly convert reservoir heat to mechanical energy for fluid recirculation. Stored pressure drives fluid production and responds faster than conventional brine-based geothermal systems. Our design uses concentric rings of horizontal wells to create a hydraulic divide that stores supplemental fluids and pressure. Production and injection wells are controlled to schedule power delivery and time-shift the parasitic power necessary to separate N2 from air and compress it for injection. The parasitic load can be scheduled during minimum power demand or when there is excess electricity from wind or solar. Net power output can nearly equal gross power output during peak demand, and energy storage is almost 100% efficient because it is achieved by the time-shift. Further, per-well production rates can take advantage of the large productivity of horizontal wells, with greater leveraging of well costs, which often constitute a major portion of capital costs for geothermal power systems.

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.

Finger-powered microfluidic systems using multilayer soft lithography and injection molding processes.

PubMed

Iwai, Kosuke; Shih, Kuan Cheng; Lin, Xiao; Brubaker, Thomas A; Sochol, Ryan D; Lin, Liwei

2014-10-07

Point-of-care (POC) and disposable biomedical applications demand low-power microfluidic systems with pumping components that provide controlled pressure sources. Unfortunately, external pumps have hindered the implementation of such microfluidic systems due to limitations associated with portability and power requirements. Here, we propose and demonstrate a 'finger-powered' integrated pumping system as a modular element to provide pressure head for a variety of advanced microfluidic applications, including finger-powered on-chip microdroplet generation. By utilizing a human finger for the actuation force, electrical power sources that are typically needed to generate pressure head were obviated. Passive fluidic diodes were designed and implemented to enable distinct fluids from multiple inlet ports to be pumped using a single actuation source. Both multilayer soft lithography and injection molding processes were investigated for device fabrication and performance. Experimental results revealed that the pressure head generated from a human finger could be tuned based on the geometric characteristics of the pumping system, with a maximum observed pressure of 7.6 ± 0.1 kPa. In addition to the delivery of multiple, distinct fluids into microfluidic channels, we also employed the finger-powered pumping system to achieve the rapid formation of both water-in-oil droplets (106.9 ± 4.3 μm in diameter) and oil-in-water droplets (75.3 ± 12.6 μm in diameter) as well as the encapsulation of endothelial cells in droplets without using any external or electrical controllers.

In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan.

PubMed

Fernández-Ferreiro, Anxo; González Barcia, Miguel; Gil-Martínez, María; Vieites-Prado, Alba; Lema, Isabel; Argibay, Barbara; Blanco Méndez, José; Lamas, Maria Jesus; Otero-Espinar, Francisco Javier

2015-08-01

Gellan gum, kappa-carrageenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use. To achieve this purpose different proportion of the biopolymers were analyzed using a mixture experimental design evaluating their transparency, mechanical properties and bioadhesion in the absence and presence of simulated tear fluid. Tear induces a rapid sol-to-gel phase transition in the mixtures forming a consistent hydrogel. The solution composed by 80% of gellan gum and 20% kappa-carrageenan showed the best mechanical and mucoadhesive properties. This mixture was evaluated for rheological behavior, microstructure, cytotoxicity, acute corneal irritancy, ex-vivo and in vivo ocular toxicity and in vivo corneal contact time using Magnetic Resonance Images (MRI) techniques. Result indicates that the system is safe at ophthalmic level and produces an extensive ocular permanence higher than 6h. Copyright © 2015 Elsevier B.V. All rights reserved.

Nonuniform Moving Boundary Method for Computational Fluid Dynamics Simulation of Intrathecal Cerebrospinal Flow Distribution in a Cynomolgus Monkey.

PubMed

Khani, Mohammadreza; Xing, Tao; Gibbs, Christina; Oshinski, John N; Stewart, Gregory R; Zeller, Jillynne R; Martin, Bryn A

2017-08-01

A detailed quantification and understanding of cerebrospinal fluid (CSF) dynamics may improve detection and treatment of central nervous system (CNS) diseases and help optimize CSF system-based delivery of CNS therapeutics. This study presents a computational fluid dynamics (CFD) model that utilizes a nonuniform moving boundary approach to accurately reproduce the nonuniform distribution of CSF flow along the spinal subarachnoid space (SAS) of a single cynomolgus monkey. A magnetic resonance imaging (MRI) protocol was developed and applied to quantify subject-specific CSF space geometry and flow and define the CFD domain and boundary conditions. An algorithm was implemented to reproduce the axial distribution of unsteady CSF flow by nonuniform deformation of the dura surface. Results showed that maximum difference between the MRI measurements and CFD simulation of CSF flow rates was <3.6%. CSF flow along the entire spine was laminar with a peak Reynolds number of ∼150 and average Womersley number of ∼5.4. Maximum CSF flow rate was present at the C4-C5 vertebral level. Deformation of the dura ranged up to a maximum of 134 μm. Geometric analysis indicated that total spinal CSF space volume was ∼8.7 ml. Average hydraulic diameter, wetted perimeter, and SAS area were 2.9 mm, 37.3 mm and 27.24 mm2, respectively. CSF pulse wave velocity (PWV) along the spine was quantified to be 1.2 m/s.

Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

NASA Astrophysics Data System (ADS)

Ensign-Hodges, Laura

A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations failed to reach. However, hypotonic formulations caused free drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. Minimally hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. We then describe an ex vivo method for characterizing particle transport on freshly excised mucosal tissues. By directly observing MPP transport on vaginal, gastrointestinal, and respiratory tissue, we were able to determine an innate difference in mucus mesh size at different anatomical locations. In addition, we were able to optimize particle size for gastrointestinal delivery in mice. As described here, there are numerous barriers to effective drug delivery in the gastrointestinal tract, including the mucus barrier. We go on to demonstrate that MPP can improve delivery in the gastrointestinal tract, both by rectal and oral administration. Finally, we describe the use of MPP for improving vaginal drug delivery. Incomplete drug coverage and short duration of action limit the effectiveness of vaginally administered drugs, including microbicides for preventing sexually transmitted infections. We show that MPP provide uniform distribution over the vaginal epithelium, whereas CP are aggregated by mouse vaginal mucus, leading to poor distribution. By penetrating into the deepest mucus layers in the rugae, more MPP were retained in the vaginal tract compared to CP. After 24 h, when delivered in a conventional vaginal gel, patches of a model drug remained on the vaginal epithelium, whereas the epithelium was coated with drug delivered by MPP. We then demonstrate that when administered 30 min prior to inoculum, anti-HSV-2 MPP protected 53% of mice compared to only 16% protected by soluble drug. Overall, MPP improved vaginal drug distribution and retention, provided more effective protection against vaginal viral challenge than soluble drug, and were non-toxic when administered daily for one week.

Micromixer based on dielectric stack actuators for medical applications

NASA Astrophysics Data System (ADS)

Solano-Arana, Susana; Klug, Florian; Mößinger, Holger; Förster-Zügel, Florentine; Schlaak, Helmut F.

2017-04-01

Based on a previously developed microperistaltic pump, a micromixer made out of dielectric elastomer stack actuators (DESA) is proposed. The micromixer will be able to mix two fluids at the microscale, pumping both fluids in and out of the device. The device consists of three chambers. In the first and second chambers, fluids A and B are hosted, while in the third chamber, fluids A and B are mixed. The fluid flow regime is laminar. The application of voltage leads to an increase of the size of a gap in the z-axis direction, due to the actuators area expansion. This makes a channel open through which the fluid flows. The frequency of the actuation of the different actuators allows an increase of the flow rate. The micromixer can be used for applications such as drug delivery and synthesis of nucleic acids, the proposed device will be made of Polydimethylsiloxane (PDMS) as dielectric and graphite powder as electrode material. PDMS is a biocompatible material, widely used in the prosthesis field. Mixing fluids at a microscale is also in need in the lab-on-achip technology for complex chemical reactions.

Novel sol-gel organic-inorganic hybrid materials for drug delivery.

PubMed

Catauro, Michelina; Verardi, Duilio; Melisi, Daniela; Belotti, Federico; Mustarelli, Piercarlo

2010-01-01

The aim of the present study was to synthetize and characterize novel sol-gel organic-inorganic hybrid materials to be used for controlled drug delivery application. Organic-inorganic hybrid class I materials based on poly(epsilon-caprolactone) (PCL 6, 12, 24 and 50 wt%) and zirconia-yttria (ZrO2-5%Y2O3) were synthesized by a sol-gel method, from a multicomponent solution containing zirconium propoxide [Zr(OC2H7)4], yttrium chloride (YCl3), PCL, water and chloroform (CHCl3). The structure of the hybrids was obtained by means of hydrogen bonds between the Zr-OH group (H-donor) in the sol-gel intermediate species and the carboxylic group (H-acceptor) in the repeating units of the polymer. The presence of hydrogen bonds between organic-inorganic components of the hybrid materials was suggested by Fourier transform infrared (FTIR) analysis, and strongly supported by solid-state NMR. A single-step, sol-gel process was then used to precipitate microspheres containing ketoprofen or indomethacin for controlled drug delivery applications. Release kinetics in a simulated body fluid (SBF) were subsequently investigated. The amount of drug released was detected by UV-VIS spectroscopy. Pure anti-inflammatory agents exhibited linear release with time, in contrast drugs entrapped in the organic-inorganic hybrids were released with a logarithmic time dependence, starting with an initial burst effect followed by a gradual decrease. The synthesis of amorphous materials containing drugs, obtained by sol-gel methods, helps to devise new strategies for controlled drug delivery system design.

Assessing Modeled CO2 Retention and Rebreathing of a Facemask Designed for Efficient Delivery of Aerosols to Infants

PubMed Central

Mundt, Christian; Sventitskiy, Alexander; Cehelsky, Jeffrey E.; Patters, Andrea B.; Tservistas, Markus; Hahn, Michael C.; Juhl, Gerd; DeVincenzo, John P.

2012-01-01

Background. New aerosol drugs for infants may require more efficient delivery systems, including face masks. Maximizing delivery efficiency requires tight-fitting masks with minimal internal mask volumes, which could cause carbon dioxide (CO2) retention. An RNA-interference-based antiviral for treatment of respiratory syncytial virus in populations that may include young children is designed for aerosol administration. CO2 accumulation within inhalation face masks has not been evaluated. Methods. We simulated airflow and CO2 concentrations accumulating over time within a new facemask designed for infants and young children (PARI SMARTMASK® Baby). A one-dimensional model was first examined, followed by 3-dimensional unsteady computational fluid dynamics analyses. Normal infant breathing patterns and respiratory distress were simulated. Results. The maximum average modeled CO2 concentration within the mask reached steady state (3.2% and 3% for normal and distressed breathing patterns resp.) after approximately the 5th respiratory cycle. After steady state, the mean CO2 concentration inspired into the nostril was 2.24% and 2.26% for normal and distressed breathing patterns, respectively. Conclusion. The mask is predicted to cause minimal CO2 retention and rebreathing. Infants with normal and distressed breathing should tolerate the mask intermittently delivering aerosols over brief time frames. PMID:22792479

Design and evaluation of novel fast forming pilocarpine-loaded ocular hydrogels for sustained pharmacological response

PubMed Central

Anumolu, SivaNaga S.; Singh, Yashveer; Gao, Dayuan; Stein, Stanley; Sinko, Patrick J.

2009-01-01

Fast forming hydrogels prepared by crosslinking a poly(ethylene glycol) (PEG)-based copolymer containing multiple thiol (SH) groups were evaluated for the controlled ocular delivery of pilocarpine and subsequent pupillary constriction. Physical properties of the hydrogels were characterized using UV-Vis spectrophotometry, transmission electron microscopy (TEM), rheometry, and swelling kinetics. Pilocarpine loading efficiency and release properties were measured in simulated tear fluid. The hydrogel formulations exhibited high drug loading efficiency (~74%). Pilocarpine release was found to be biphasic with release half times of ~2 and 94 h, respectively, and 85–100% of the drug was released over 8-days. Pilocarpine-loaded (2% w/v) hydrogels were evaluated in a rabbit model and compared to a similar dose of drug in aqueous solution. The hydrogels were retained in the eye for the entire period of the study with no observed irritation. Pilocarpine-loaded hydrogels sustained pupillary constriction for 24 h after administration as compared to 3 h for the solution, an 8-fold increase in duration of action. A strong correlation between pilocarpine release and pupillary response was observed. In conclusion, the current studies demonstrate that in situ forming PEG hydrogels possess the viscoelastic, retention, and sustained delivery properties required for an efficient ocular drug delivery system. PMID:19341773

Inner layer-embedded contact lenses for pH-triggered controlled ocular drug delivery.

PubMed

Zhu, Qiang; Liu, Chang; Sun, Zheng; Zhang, Xiaofei; Liang, Ning; Mao, Shirui

2018-07-01

Contact lenses (CLs) are ideally suited for controlled ocular drug delivery, but are limited by short release duration, poor storage stability and low drug loading. In this study, we present a novel inner layer-embedded contact lens capable of pH-triggered extended ocular drug delivery with good storage stability. Blend film of ethyl cellulose and Eudragit S100 was used as the inner layer, while pHEMA hydrogel was used as outer layer to fabricate inner layer-embedded contact lens. Using diclofenac sodium(DS) as a drug model, influence of polymer ratio in the blend film, EC viscosity, drug/polymer ratio, inner layer thickness and outlayer thickness of pHEMA hydrogel on drug release behavior was studied and optimized for daily use. The pH-triggered drug eluting pattern enables the inner layer-embedded contact lens being stored in phosphate buffer solution pH 6.8 with ignorable drug loss and negligible changes in drug release pattern. In vivo pharmacokinetic study in rabbits showed sustained drug release for over 24 h in tear fluid, indicating significant improvement in drug corneal residence time. A level A IVIVC was established between in vitro drug release and in vivo drug concentration in tear fluid. In conclusion, this inner layer embedded contact lens design could be used as a platform for extended ocular drug delivery with translational potential for both anterior and posterior ocular diseases therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical applications of magnetic nanoparticles for hyperthermia.

PubMed

Thiesen, Burghard; Jordan, Andreas

2008-09-01

Magnetic fluids are increasingly used for clinical applications such as drug delivery, magnetic resonance imaging and magnetic fluid hyperthermia. The latter technique that has been developed as a cancer treatment for several decades comprises the injection of magnetic nanoparticles into tumors and their subsequent heating in an alternating magnetic field. Depending on the applied temperature and the duration of heating this treatment either results in direct tumor cell killing or makes the cells more susceptible to concomitant radio- or chemotherapy. Numerous groups are working in this field worldwide, but only one approach has been tested in clinical trials so far. Here, we summarize the clinical data gained in these studies on magnetic fluid induced hyperthermia.

Micellar emulsions composed of mPEG-PCL/MCT as novel nanocarriers for systemic delivery of genistein: a comparative study with micelles

PubMed Central

Zhang, Tianpeng; Wang, Huan; Ye, Yanghuan; Zhang, Xingwang; Wu, Baojian

2015-01-01

Polymeric micelles receive considerable attention as drug delivery vehicles, depending on the versatility in drug solubilization and targeting therapy. However, their use invariably suffers with poor stability both in in vitro and in vivo conditions. Here, we aimed to develop a novel nanocarrier (micellar emulsions, MEs) for a systemic delivery of genistein (Gen), a poorly soluble anticancer agent. Gen-loaded MEs (Gen-MEs) were prepared from methoxy poly(ethylene glycol)-block-(ε-caprolactone) and medium-chain triglycerides (MCT) by solvent-diffusion technique. Nanocarriers were characterized by dynamic light scattering, transmission electron microscopy, and in vitro release. The resulting Gen-MEs were approximately 46 nm in particle size with a narrow distribution. Gen-MEs produced a different in vitro release profile from the counterpart of Gen-ME. The incorporation of MCT significantly enhanced the stability of nanoparticles against dilution with simulated body fluid. Pharmacokinetic study revealed that MEs could notably extend the mean retention time of Gen, 1.57- and 7.38-fold as long as that of micelles and solution formulation, respectively, following intravenous injection. Furthermore, MEs markedly increased the elimination half-life (t1/2β) of Gen, which was 2.63-fold larger than that of Gen solution. Interestingly, Gen distribution in the liver and kidney for MEs group was significantly low relative to the micelle group in the first 2 hours, indicating less perfusion in such two tissues, which well accorded with the elongated mean retention time. Our findings suggested that MEs may be promising carriers as an alternative of micelles to systemically deliver poorly soluble drugs. PMID:26491290

Self-emulsifying drug delivery systems: Design of a novel vaginal delivery system for curcumin.

PubMed

Köllner, S; Nardin, I; Markt, R; Griesser, J; Prüfert, F; Bernkop-Schnürch, A

2017-06-01

The aim of this study was to develop a vaginal self-emulsifying delivery system for curcumin being capable of spreading, of permeating the mucus gel layer and of protecting the drug being incorporated in oily nanodroplets towards mucus interactions and immobilization. The emulsifying properties of curcumin loaded SEDDS containing 30% Cremophor RH40, 20% Capmul PG-8, 30% Captex 300, 10% DMSO and 10% tetraglycol (SEDD formulation A) as well as 25% PEG 200, 35% Cremophor RH40, 20% Captex 355, 10% Caprylic acid and 10% Tween 80 (SEDD formulation B) after diluting 1+2 with artificial vaginal fluid were characterized regarding droplet size and zeta potential. Collagen swelling test was used to examine the irritation potential of SEDDS. Additionally to mucus binding studies, permeation studies in the mucus were performed. Furthermore, spreading potential of the novel developed formulations was compared with a commercial available o/w cream (non-ionic hydrophilic cream) on vaginal mucosa. SEDDS displayed a mean droplet size between 38 and 141nm and a zeta potential of -0.3 to -1.6mV. The collagen swelling test indicated no significant irritation potential of both formulations over 24h. An immediate interaction of unformulated curcumin with the mucus was determined, whereas both SEDDS facilitated drug permeation through the mucus layer. Formulation B showed a 2.2-fold improved transport ratio of curcumin compared to SEDD formulation A. In comparison to the vaginal cream, SEDD formulation A and B were able to spread over the vaginal mucosa and cover the tissue to a 17.8- and 14.8-fold higher extent, respectively. According to these results, SEDDS seems to be a promising tool for vaginal application. Copyright © 2017 Elsevier B.V. All rights reserved.