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Sample records for aerosol delivery system

  1. Aerosolization of lipoplexes using AERx Pulmonary Delivery System.

    PubMed

    Deshpande, Deepa; Blanchard, James; Srinivasan, Sudarshan; Fairbanks, Dallas; Fujimoto, Jun; Sawa, Teiji; Wiener-Kronish, Jeanine; Schreier, Hans; Gonda, Igor

    2002-01-01

    The lung represents an attractive target for delivering gene therapy to achieve local and potentially systemic delivery of gene products. The objective of this study was to evaluate the feasibility of the AERx Pulmonary Delivery System for delivering nonviral gene therapy formulations to the lung. We found that "naked" DNA undergoes degradation following aerosolization through the AERx nozzle system. However, DNA formulated with a molar excess of cationic lipids (lipoplexes) showed no loss of integrity. In addition, the lipoplexes showed no significant change in particle size, zeta (zeta) potential, or degree of complexation following extrusion. The data suggest that complexation with cationic lipids had a protective effect on the formulation following extrusion. In addition, there was no significant change in the potency of the formulation as determined by a transfection study in A-549 cells in culture. We also found that DNA formulations prepared in lactose were aerosolized poorly. Significant improvements in aerosolization efficiency were seen when electrolytes such as NaCl were added to the formulation. In conclusion, the data suggest that delivery of lipoplexes using the AERx Pulmonary Delivery System may be a viable approach for pulmonary gene therapy. PMID:12423062

  2. The expanding role of aerosols in systemic drug delivery, gene therapy, and vaccination.

    PubMed

    Laube, Beth L

    2005-09-01

    Aerosolized medications have been used for centuries to treat respiratory diseases. Until recently, inhalation therapy focused primarily on the treatment of asthma and chronic obstructive pulmonary disease, and the pressurized metered-dose inhaler was the delivery device of choice. However, the role of aerosol therapy is clearly expanding beyond that initial focus. This expansion has been driven by the Montreal protocol and the need to eliminate chlorofluorocarbons (CFCs) from traditional metered-dose inhalers, by the need for delivery devices and formulations that can efficiently and reproducibly target the systemic circulation for the delivery of proteins and peptides, and by developments in medicine that have made it possible to consider curing lung diseases with aerosolized gene therapy and preventing epidemics of influenza and measles with aerosolized vaccines. Each of these drivers has contributed to a decade or more of unprecedented research and innovation that has altered how we think about aerosol delivery and has expanded the role of aerosol therapy into the fields of systemic drug delivery, gene therapy, and vaccination. During this decade of innovation, we have witnessed the coming of age of dry powder inhalers, the development of new soft mist inhalers, and improved pressurized metered-dose inhaler delivery as a result of the replacement of CFC propellants with hydrofluoroalkane. The continued expansion of the role of aerosol therapy will probably depend on demonstration of the safety of this route of administration for drugs that have their targets outside the lung and are administered long term (eg, insulin aerosol), on the development of new drugs and drug carriers that can efficiently target hard-to-reach cell populations within the lungs of patients with disease (eg, patients with cystic fibrosis or lung cancer), and on the development of devices that improve aerosol delivery to infants, so that early intervention in disease processes with aerosol

  3. Alveolar targeting of aerosol pentamidine. Toward a rational delivery system

    SciTech Connect

    Simonds, A.K.; Newman, S.P.; Johnson, M.A.; Talaee, N.; Lee, C.A.; Clarke, S.W. )

    1990-04-01

    Nebulizer systems that deposit a high proportion of aerosolized pentamidine on large airways are likely to be associated with marked adverse side effects, which may lead to premature cessation of treatment. We have measured alveolar deposition and large airway-related side effects (e.g., cough, breathlessness, and effect on pulmonary function) after aerosolization of 150 mg pentamidine isethionate labeled with {sup 99m}Tc-Sn-colloid. Nine patients with AIDS were studied using three nebulizer systems producing different droplet size profiles: the Acorn System 22, Respirgard II, and Respirgard II with the inspiratory baffle removed. Alveolar deposition was greatest and side effects least with the nebulizer producing the smallest droplet size profile (Respirgard II), whereas large airway-related side effects were prominent and alveolar deposition lowest with the nebulizer producing the largest droplet size (Acorn System 22). Values for alveolar deposition and adverse airway effects were intermediate using the Respirgard with inspiratory baffle removed, thus indicating the importance of the baffle valve in determining droplet size. Addition of a similar baffle valve to the Acorn System 22 produced a marked improvement in droplet size profile. Selection of a nebulizer that produces an optimal droplet size range offers the advantage of enhancing alveolar targeting of aerosolized pentamidine while reducing large airway-related side effects.

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

    PubMed

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

    2014-11-01

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

  5. Clinical assessment of a commercial aerosol delivery system for ventilation scanning by comparison with KR-81m

    SciTech Connect

    Wollmer, P.; Eriksson, L.; Andersson, A.C.

    1984-01-01

    Radioactive aerosols offer a means for steady state ventilation scanning in multiple views. The clinical use of radioaerosol techniques has been hampered by the lack of delivery systems producing sufficiently small particles. If the aerosol contains large particles, heavy deposition occurs in major airways, especially in patients with airways disease. The authors have assessed a new, commercial aerosol delivery system (Syntevent) by comparison with Kr-81m ventilation scanning in 23 patients with airways obstruction. An indirect comparison was also made with a settling bad technique. Ventilation scans in four projections were obtained during continuous inhalation of Kr-81m. Subsequently, the patient inhaled an aerosol labelled with In-113m from the Syntevent system, and aerosol ventilation scans were obtained in the same projections. Spirometry was performed to establish the degree of airways obstruction. The aerosol delineated the ventilated regions of the lungs adequately in all the patients. Deposition of aerosol in larger airways was seen in a few patients only, and this did not impede the interpretation of the scintigram. A quantitative analysis of the penetration of the aerosol to the periphery of the lung failed to demonstrate any significant correlation between particle penetration and airways obstruction. Aerosol penetration was significantly greater (p<0.001) with the Syntevent system than with a settling bag technique.

  6. Rationale for the selection of an aerosol delivery system for gene delivery.

    PubMed

    Lentz, Yvonne K; Anchordoquy, Thomas J; Lengsfeld, Corinne S

    2006-01-01

    Genetic therapeutics show great promise toward the treatment of illnesses associated with the lungs; however, current methods of delivery such as jet and ultrasonic nebulization decrease the activity and effectiveness of these treatments. Extremely low transfection rates exhibited by non-complexed plasmid DNA in these nebulizers have been primarily attributed to poor translocation and loss of molecular integrity as a consequence of shear-induced degradation. Current research focusing on methods to increase transfection rates via the pulmonary delivery route has largely concentrated on the incorporation of carbon dioxide in the air stream to increase breath depth as well as the addition of cationic agents that condense DNA into compact, ordered complexes. The purpose of this study was to examine the impact of several classic as well as the latest atomization devices on the structure of non-complexed DNA. Various sizes of plasmid and cosmid DNA were processed through an electrostatic spray, ultrasonic nebulizer, vibrating mesh nebulizer, and jet nebulizer. Results varied dramatically based upon atomization device as well as DNA size. This may explain the inefficiency experienced by genetic therapeutics during pulmonary delivery. More importantly, this suggests that the selection of an atomization device should consider DNA size in order to achieve optimal gene delivery to the lungs. PMID:17034312

  7. Other medications for aerosol delivery.

    PubMed

    Rubin, Bruce K

    2006-01-01

    Although aerosol therapy is most commonly used to treat asthma and COPD, there are a large number of aerosol medications now used or in development for other diseases. Mucoactive agents have long been available by aerosol, but now we have truly effective drugs to improve effective airway clearance including dornase alfa, hyperosmolar saline, and aerosol surfactant. Inhaled antibiotics are available for the treatment of cystic fibrosis, bronchiectasis and other chronic airway infections. With the development of devices that can target aerosol to the deep lung, the opportunity to deliver medications systemically by the aerosol route has become a reality. Insulin, recently approved in the US as aerosol therapy, and other peptides are systemically absorbed from the distal airway and alveolus. Aerosol gene transfer therapy to correct abnormalities associated with cystic fibrosis, primary ciliary dyskinesia and other airway diseases also holds great potential. PMID:16798603

  8. Year in Review 2014: Aerosol Delivery Devices.

    PubMed

    Myers, Timothy R

    2015-08-01

    After centuries of discoveries and technological growth, aerosol therapy remains a cornerstone of care in the management of both acute and chronic respiratory conditions. Aerosol therapy embraces the concept that medicine is both an art and a science, where an explicit understanding of the science of aerosol therapy, the nuances of the different delivery devices, and the ability to provide accurate and reliable education to patients become increasingly important. The purpose of this article is to review recent literature regarding aerosol delivery devices in a style that readers of Respiratory Care may use as a key topic resource. PMID:26038596

  9. Multifunctional SMA-based smart inhaler system for improved aerosol drug delivery: design and fabrication

    NASA Astrophysics Data System (ADS)

    Pausley, Matthew E.; Seelecke, Stefan

    2008-03-01

    This paper documents the development of a prototype smart aerosol drug inhaler system using shape memory alloy (SMA) actuators. Unlike conventional dispersed-release inhalers, the smart inhaler system releases the aerosol drug in a very small area within the mouth inlet. Kleinstreuer and Zhang [1] have found that controlled release in the mouth inlet increases drug efficiency and allows targeting of specific sites within the lung. The methodology has been validated numerically and experimentally using fixed-exit position inhalers. The design presented in this work, however, allows for variation of nozzle exit position using SMA wire actuators in a combined actuator/sensor role. In contrast to other possible mechanisms, SMA wires are lightweight, require low power, and are the least obstructive to the flow of air through the inhaler. The dual actuator/sensor nature of the SMA wires (via resistance measurement) further simplifies the design. Solutions and insights into several SMA actuator design challenges are presented. SMA wire actuator characteristics such as achievable stroke and their effect on the design are highlighted. Consideration of actuator force requirements and the capabilities of SMA wires and studied. The problems posed by the thermal characteristics of SMA wires and innovative solutions are reported.

  10. 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

  11. Pulmonary drug delivery by powder aerosols.

    PubMed

    Yang, Michael Yifei; Chan, John Gar Yan; Chan, Hak-Kim

    2014-11-10

    The efficacy of pharmaceutical aerosols relates to its deposition in the clinically relevant regions of the lungs, which can be assessed by in vivo lung deposition studies. Dry powder formulations are popular as devices are portable and aerosolisation does not require a propellant. Over the years, key advancements in dry powder formulation, device design and our understanding on the mechanics of inhaled pharmaceutical aerosol have opened up new opportunities in treatment of diseases through pulmonary drug delivery. This review covers these advancements and future directions for inhaled dry powder aerosols. PMID:24818765

  12. Targeted Lung Delivery of Nasally Administered Aerosols

    PubMed Central

    Tian, Geng; Hindle, Michael; Longest, P. Worth

    2014-01-01

    Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages including co-administration during non-invasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1–2.6x, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35x. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions. PMID:24932058

  13. Aerosol delivery of synthetic lung surfactant

    PubMed Central

    Hernández-Juviel, José M.; Waring, Alan J.

    2014-01-01

    Background. Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in premature infants with respiratory distress syndrome due to lack of lung surfactant. If this approach fails, the next step is often intubation, mechanical ventilation (MV) and intratracheal instillation of clinical lung surfactant. Objective. To investigate whether aerosol delivery of advanced synthetic lung surfactant, consisting of peptide mimics of surfactant proteins B and C (SP-B and SP-C) and synthetic lipids, during nCPAP improves lung function in surfactant-deficient rabbits. Methods. Experimental synthetic lung surfactants were produced by formulating 3% Super Mini-B peptide (SMB surfactant), a highly surface active SP-B mimic, and a combination of 1.5% SMB and 1.5% of the SP-C mimic SP-Css ion-lock 1 (BC surfactant), with a synthetic lipid mixture. After testing aerosol generation using a vibrating membrane nebulizer and aerosol conditioning (particle size, surfactant composition and surface activity), we investigated the effects of aerosol delivery of synthetic SMB and BC surfactant preparations on oxygenation and lung compliance in saline-lavaged, surfactant-deficient rabbits, supported with either nCPAP or MV. Results. Particle size distribution of the surfactant aerosols was within the 1–3 µm distribution range and surfactant activity was not affected by aerosolization. At a dose equivalent to clinical surfactant therapy in premature infants (100 mg/kg), aerosol delivery of both synthetic surfactant preparations led to a quick and clinically relevant improvement in oxygenation and lung compliance in the rabbits. Lung function recovered to a greater extent in rabbits supported with MV than with nCPAP. BC surfactant outperformed SMB surfactant in improving lung function and was associated with higher phospholipid values in bronchoalveolar lavage fluid; these findings were irrespective of the type of ventilatory support

  14. Acute hemodynamic effects of nebulized iloprost via the I-neb Adaptive Aerosol Delivery system in pulmonary hypertension

    PubMed Central

    Richter, Manuel J.; Ghofrani, Hossein A.; Voswinckel, Robert; Seeger, Werner; Schulz, Richard; Reichenberger, Frank

    2015-01-01

    Abstract Inhaled iloprost has proven to be an effective therapy in patients with pulmonary hypertension (PH). However, the acute hemodynamic effect of nebulized iloprost delivered via the I-neb Adaptive Aerosol Delivery (AAD) system remains unclear and needs to be assessed. In this study, 126 patients with PH were classified according to current guidelines (59, 34, 29, and 4 patients in groups 1/1′, 3, 4, and 5, respectively; 20 patients had idiopathic pulmonary arterial hypertension [iPAH]), were randomly assigned to inhale iloprost 2.5 g (n = 67) or 5.0 g (n = 59) via the I-neb AAD system, and were assessed by right heart catheterization. In seven patients with iPAH, iloprost plasma levels were measured. The two iloprost doses caused decreases from baseline in pulmonary vascular resistance (PVR; 2.5 g: –14.7%; 5.0 g: –15.6%) and mean pulmonary arterial pressure (mPAP; 2.5 g: –11.0%; 5.0 g: –10.1%) while cardiac index (CI) increased (2.5 g: +6.5%; 5.0 g: +6.4%). The subset with iPAH also showed decreases from baseline in PVR and mPAP and an increase in CI. Peak iloprost plasma levels showed no significant difference after inhalation of 2.5 g or 5.0 g iloprost (95.5 pg/mL vs. 73.0 pg/mL; P = 0.06). In summary, nebulized iloprost delivered via the I-neb AAD system reduced mPAP and PVR and increased CI from baseline in a heterogeneous group of patients with PH and in the subset with iPAH. In patients with iPAH, inhalation of 2.5 g or 5.0 g iloprost resulted in broadly similar peak iloprost plasma levels. PMID:25992279

  15. Multistage pH-responsive mucoadhesive nanocarriers prepared by aerosol flow reactor technology: A controlled dual protein-drug delivery system.

    PubMed

    Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca; Mäkilä, Ermei; Raula, Janne; Kauppinen, Esko I; Salonen, Jarno; Sarmento, Bruno; Hirvonen, Jouni; Santos, Hélder A

    2015-11-01

    Nanotechnology based drug delivery systems are anticipated to overcome the persistent challenges in oral protein and peptide administration, and lead to the development of long awaited non-invasive therapies. Herein, an advanced single-step aerosol flow reactor based technology was used to develop a multifunctional site specific dual protein-drug delivery nanosystem. For this purpose, mucoadhesive porous silicon (PSi) nanoparticles encapsulated into a pH-responsive polymeric nanomatrix was developed for advanced oral type 2 diabetes mellitus therapy with an antidiabetic peptide, glucagon like peptide-1 (GLP-1), and the enzyme inhibitor, dipeptidyl peptidase-4 (DPP4). Chitosan surface modification inherited the mucoadhesiveness to the nanosystem which led to enhanced cellular interactions and increased cellular compatibility. An advanced aerosol flow reactor technology was used to encapsulate the chitosan modified nanoparticles into an enteric polymeric nanomatrix. The pH-sensitive polymeric matrix simultaneously prevented the gastric degradation of the encapsulated peptide and also preserved the mucoadhesive functionality of the chitosan-modified PSi nanoparticles in the harsh stomach environment. The multidrug loaded nanosystem showed augmented intestinal permeability of GLP-1, evaluated in an in vitro cell-based intestinal epithelium model, attributed to the permeation enhancer effect of chitosan and inhibition of GLP-1 degradation by the DPP4 inhibitor. The applied technology resulted in the development of a dual-drug delivery nanosystem that synergizes the antidiabetic effect of the loaded peptide and the enzyme inhibitor, thereby indicating high clinical potential of the system and preparation technique. PMID:26253804

  16. Aerosol Droplet Delivery of Mesoporous Silica Nanoparticles: A Strategy for Respiratory-Based Therapeutics

    PubMed Central

    Li, Xueting; Xue, Min; Raabe, Otto G.; Aaron, Holly L.; Eisen, Ellen A.; Evans, James E.; Hayes, Fred A.; Inaga, Sumire; Tagmout, Abderrahmane; Takeuchi, Minoru; Vulpe, Chris; Zink, Jeffrey I.; Risbud, Subhash H.; Pinkerton, Kent E.

    2015-01-01

    A highly versatile nanoplatform that couples mesoporous silica nanoparticles (MSN) with an aerosol technology to achieve direct nanoscale delivery to the respiratory tract is described. This novel method can deposit MSN nanoparticles throughout the entire respiratory tract, including nasal, tracheobronchial and pulmonary regions using a water-based aerosol. This delivery method was successfully tested in mice by inhalation. The MSN nanoparticles used have the potential for carrying and delivering therapeutic agents to highly specific target sites of the respiratory tract. The approach provides a critical foundation for developing therapeutic treatment protocols for a wide range of diseases where aerosol delivery to the respiratory system would be desirable. PMID:25819886

  17. Pathophysiological and disease constraints on aerosol delivery

    SciTech Connect

    Gerrity, T.R.

    1989-01-01

    The dose of inhaled particles to the respiratory tract depends upon many factors. These factors include the size of the particles, the pattern of breathing (flow and tidal volume), the physical properties of the articles (hygroscopic or non-hygroscopic), anatomy of the respiratory tract, and the pathophysiologic status of the respiratory tract. In addition to these factors, which are primarily related to the deposition of particles, the rate of particle clearance from the respiratory tract also influences the dose of particles. The paper is a review of the various factors influencing dose of inhaled particles to the respiratory tract. The emphasis of the paper is on therapeutic aerosol particles, though the principals discussed also apply to toxic particles as well. An important area of consideration is the influence of disease on the delivery of particle dose. From the point of view of toxic particles this is important when considering potential susceptible populations.

  18. 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

  19. 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. PMID:25267660

  20. Improving Pharmaceutical Aerosol Delivery During Noninvasive Ventilation: Effects of Streamlined Components

    PubMed Central

    Longest, P. Worth; Golshahi, Laleh; Hindle, Michael

    2013-01-01

    Aerosol delivery efficiency during noninvasive ventilation (NIV) is known to be low (~10%) and is associated with poor outcomes of aerosol therapy. The objective of this study was to demonstrate the benefit of redesigning ventilation circuit components using a streamlining approach to improve aerosol delivery during nasal high flow therapy in adults with a conventional-sized aerosol from a mesh nebulizer. The ventilation circuit consisted of a humidifier, mesh nebulizer, mixing T-connector (with 90° angle), 10 mm tubing, and nasal cannula interface. In vitro experiments and computational fluid dynamics analyses were used to evaluate depositional losses in a system of existing components and a newly proposed streamlined T-connector and cannula at flow rates of 30 and 45 LPM. Streamlined designs reduced deposition in the T-connector by a factor of 4. In the nasal cannula, the streamlined designs reduced depositional losses by factors of 1.25–2.0. With the streamlined designs, the highest emitted dose achieved was >40% for a conventional-sized aerosol at 30 LPM. Streamlined geometries offer an effective method to significantly improve the delivery of aerosols through components of NIV systems. This increase in delivery efficiency is important for new inhaled medications with narrow therapeutic windows, increased costs, or long delivery times. PMID:23423706

  1. Drug delivery systems: An updated review

    PubMed Central

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

    2012-01-01

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

  2. Optimal Delivery of Aerosols to Infants During Mechanical Ventilation

    PubMed Central

    Azimi, Mandana; Hindle, Michael

    2014-01-01

    Abstract Purpose: The objective of this study was to determine optimal aerosol delivery conditions for a full-term (3.6 kg) infant receiving invasive mechanical ventilation by evaluating the effects of aerosol particle size, a new wye connector, and timing of aerosol delivery. Methods: In vitro experiments used a vibrating mesh nebulizer and evaluated drug deposition fraction and emitted dose through ventilation circuits containing either a commercial (CM) or new streamlined (SL) wye connector and 3-mm endotracheal tube (ETT) for aerosols with mass median aerodynamic diameters of 880 nm, 1.78 μm, and 4.9 μm. The aerosol was released into the circuit either over the full inhalation cycle (T1 delivery) or over the first half of inhalation (T2 delivery). Validated computational fluid dynamics (CFD) simulations and whole-lung model predictions were used to assess lung deposition and exhaled dose during cyclic ventilation. Results: In vitro experiments at a steady-state tracheal flow rate of 5 L/min resulted in 80–90% transmission of the 880-nm and 1.78-μm aerosols from the ETT. Based on CFD simulations with cyclic ventilation, the SL wye design reduced depositional losses in the wye by a factor of approximately 2–4 and improved lung delivery efficiencies by a factor of approximately 2 compared with the CM device. Delivery of the aerosol over the first half of the inspiratory cycle (T2) reduced exhaled dose from the ventilation circuit by a factor of 4 compared with T1 delivery. Optimal lung deposition was achieved with the SL wye connector and T2 delivery, resulting in 45% and 60% lung deposition for optimal polydisperse (∼1.78 μm) and monodisperse (∼2.5 μm) particle sizes, respectively. Conclusions: Optimization of selected factors and use of a new SL wye connector can substantially increase the lung delivery efficiency of medical aerosols to infants from current values of <1–10% to a range of 45–60%. PMID:24299500

  3. 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

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

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

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

  5. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

    Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

  6. Delivery of aerosolized drugs encapsulated in liposomes

    SciTech Connect

    Cheng, Yung-Sung; Lyons, C.R.; Schmid, M.H.

    1995-12-01

    Mycobacterium tuberculosis (Mtb) is an infectious disease that resides in the human lung. Due to the difficulty in completely killing off the disease in infected individuals, Mtb has developed drug-resistant forms and is on the rise in the human population. Therefore, ITRI and the University of New Mexico are collaborating to explore the treatment of Mtb by an aerosolized drug delivered directly to the lungs. In conclusion, it is feasible to obtain an appropriate size and concentration of the liposomes before and after aerosolization.

  7. Drug delivery systems.

    PubMed

    Robinson, D H; Mauger, J W

    1991-10-01

    New and emerging drug delivery systems for traditional drugs and the products of biotechnology are discussed, and the role of the pharmacist in ensuring the appropriate use of these systems is outlined. Advantages of advanced drug delivery systems over traditional systems are the ability to deliver a drug more selectively to a specific site; easier, more accurate, less frequent dosing; decreased variability in systemic drug concentrations; absorption that is more consistent with the site and mechanism of action; and reductions in toxic metabolites. Four basic strategies govern the mechanisms of advanced drug delivery: physical, chemical, biological, and mechanical. Oral drug delivery systems use natural and synthetic polymers to deliver the product to a specific region in the gastrointestinal tract in a timely manner that minimizes adverse effects and increases drug efficacy. Innovations in injectable and implantable delivery systems include emulsions, particulate delivery systems, micromolecular products and macromolecular drug adducts, and enzymatic-controlled delivery. Options for noninvasive drug delivery include the transdermal, respiratory, intranasal, ophthalmic, lymphatic, rectal, intravaginal, and intrauterine routes as well as topical application. Rapid growth is projected in the drug delivery systems market worldwide in the next five years. Genetic engineering has mandated the development of new strategies to deliver biotechnologically derived protein and peptide drugs and chemoimmunoconjugates. The role of the pharmacist in the era of advanced drug delivery systems will be broad based, including administering drugs, compounding, calculating dosages based on pharmacokinetic and pharmacodynamic monitoring, counseling, and research. The advent of advanced drug delivery systems offers pharmacists a new opportunity to assume an active role in patient care. PMID:1772110

  8. Inhalable PEGylated Phospholipid Nanocarriers and PEGylated Therapeutics for Respiratory Delivery as Aerosolized Colloidal Dispersions and Dry Powder Inhalers

    PubMed Central

    Muralidharan, Priya; Mallory, Evan; Malapit, Monica; Hayes Jr., Don; Mansour, Heidi M.

    2014-01-01

    Nanomedicine is making groundbreaking achievements in drug delivery. The versatility of nanoparticles has given rise to its use in respiratory delivery that includes inhalation aerosol delivery by the nasal route and the pulmonary route. Due to the unique features of the respiratory route, research in exploring the respiratory route for delivery of poorly absorbed and systemically unstable drugs has been increasing. The respiratory route has been successfully used for the delivery of macromolecules like proteins, peptides, and vaccines, and continues to be examined for use with small molecules, DNA, siRNA, and gene therapy. Phospholipid nanocarriers are an attractive drug delivery system for inhalation aerosol delivery in particular. Protecting these phospholipid nanocarriers from pulmonary immune system attack by surface modification by polyethylene glycol (PEG)ylation, enhancing mucopenetration by PEGylation, and sustaining drug release for controlled drug delivery are some of the advantages of PEGylated liposomal and proliposomal inhalation aerosol delivery. This review discusses the advantages of using PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery through the nasal and pulmonary routes as inhalation aerosols. PMID:24955820

  9. Aerosol delivery in ventilated newborn pigs: an MRI evaluation.

    PubMed

    Sood, Beena G; Shen, Yimin; Latif, Zahid; Chen, Xinguang; Sharp, Jody; Neelavalli, Jaladhar; Joshi, Aparna; Slovis, Thomas L; Haacke, E M

    2008-08-01

    Pulmonary deposition of inhaled drugs in ventilated neonates has not been studied in vivo. The objective of this study was to evaluate pulmonary delivery of gadopentetate dimeglumine (Gd-DTPA) following nebulization in ventilated piglets using magnetic resonance imaging. Seven ventilated piglets (5 +/- 2 d old, weight 1.8 +/- 0.5 kg) were scanned in the Bruker/Siemens 4T magnetic resonance scanner using T1 weighted spin-echo sequence. Aerosols of Gd-DTPA were generated continuously using the MiniHeart jet nebulizer. Breath-hold coronal images were obtained before and every 10 min during aerosolized Gd-DTPA for 90 min. Signal intensity (SI) changes over the lungs, kidneys, liver, skeletal muscle, and heart were evaluated. A significant increase in SI was observed in the lungs, kidney, and liver at 10, 20, and 40 min respectively after start of aerosol. At the end of 90 min, the SI increased by 95%, 101%, and 426% over the right lung, left lung, and kidney, respectively. A much smaller increase in SI was observed over the liver. In conclusion, we have demonstrated effective pulmonary aerosol delivery within 10 min of contrast nebulization in ventilated piglets. Contrast visualization in the kidneys within 20 min of aerosol initiation reflects alveolar absorption, glomerular filtration and renal concentration. PMID:18391839

  10. Drug delivery to paranasal sinuses using pulsating aerosols.

    PubMed

    Möller, Winfried; Schuschnig, Uwe; Bartenstein, Peter; Meyer, Gabriele; Häussinger, Karl; Schmid, Otmar; Becker, Sven

    2014-08-01

    Chronic rhinosinusitis (CRS) is the major disorder of the upper airways, affecting about 10-15% of the total population. Topical treatment regimens show only modest efficacy, because drug delivery to the posterior nose and paranasal sinuses is still a challenge. Therefore, there is a high rate of functional endoscopic sinus surgery in CRS patients. Most nasally administered aerosolized drugs, like nasal pump sprays, are efficiently filtered by the nasal valve and do not reach the posterior nasal cavity and the sinuses, which are poorly ventilated. However, as highlighted in this review, sinus ventilation and paranasal aerosol delivery can be achieved by using pulsating airflow, offering new topical treatment options for nasal disorders. Radioaerosol inhalation and imaging studies in nasal casts and in healthy volunteers have shown 4-6% of the nasally administered dose within the sinuses. In CRS patients, significant aerosol deposition in the sinus cavities was reported before sinus surgery. After surgery, deposition increased to the amount observed in healthy volunteers. In addition, compared with nasal pump sprays, retention kinetics of the radiolabel deposited in the nasal cavity was prolonged, both in healthy volunteers and in CRS patients. These efficiencies may be sufficient for topical aerosol therapies of sinus disorders and, due to the prolonged retention kinetics, may reduce application modes, but have to be proven in future clinical trials. Pulsating aerosols may offer additional new topical treatment options of nasal and sinus disorders before as well as after surgery. PMID:25084017

  11. Evaluation of Aerosol Delivery of Nanosuspension for Pre-clinical Pulmonary Drug Delivery

    NASA Astrophysics Data System (ADS)

    Chiang, Po-Chang; Alsup, Jason W.; Lai, Yurong; Hu, Yiding; Heyde, Bruce R.; Tung, David

    2009-03-01

    Asthma and chronic obstructive pulmonary disease (COPD) are pulmonary diseases that are characterized by inflammatory cell infiltration, cytokine production, and airway hyper-reactivity. Most of the effector cells responsible for these pathologies reside in the lungs. One of the most direct ways to deliver drugs to the target cells is via the trachea. In a pre-clinical setting, this can be achieved via intratracheal (IT), intranasal (IN), or aerosol delivery in the desired animal model. In this study, we pioneered the aerosol delivery of a nanosuspension formulation in a rodent model. The efficiency of different dosing techniques and formulations to target the lungs were compared, and fluticasone was used as the model compound. For the aerosol particle size determination, a ten-stage cascade impactor was used. The mass median aerodynamic diameter (MMAD) was calculated based on the percent cumulative accumulation at each stage. Formulations with different particle size of fluticasone were made for evaluation. The compatibility of regular fluticasone suspension and nanosuspension for aerosol delivery was also investigated. The in vivo studies were conducted on mice with optimized setting. It was found that the aerosol delivery of fluticasone with nanosuspension was as efficient as intranasal (IN) dosing, and was able to achieve dose dependent lung deposition.

  12. Introduction: Aerosol delivery of orally inhaled agents.

    PubMed

    Corcoran, Timothy E; Devadason, Sunalene G; Kuehl, Philip J

    2012-12-01

    Deposition scintigraphy methods have been used extensively to provide qualitative and quantitative data on aerosol drug deposition in the lungs. However, differences in methodology among the different centers performing these studies have limited the application of these techniques, especially in regulatory roles. As an introduction to the standardized techniques developed by the International Society for Aerosols in Medicine (ISAM) Regulatory Affairs Networking Group, we present potential advantages of the use of standard techniques for deposition scintigraphy. Specifically, we propose that standardized techniques would allow for better comparisons between labs and would facilitate multicenter studies. They would allow for improved methods of establishing equivalence and could be better utilized to establish dosing for new medications. They would allow for the performance of more accurate dose ranging or multidose studies and complement pharmacokinetic studies of new inhaled medications. Standardized techniques could help to establish the relationship between the deposition of drug in the lungs and clinical effect, and may also facilitate clinical measurements of deposited dose for medications with narrow therapeutic indices. In the sections that follow, we discuss the best techniques used to perform deposition scintigraphy through planar, single-photon emission computed tomography, and positron emission tomography modalities and propose a detailed set of standardized methods for each. These include methods for radiolabel validation, radiolabel accountability and mass balance, and imaging acquisition and analysis. PMID:23215846

  13. Pulmonary delivery of vancomycin dry powder aerosol to intubated rabbits

    PubMed Central

    Sullivan, Bradley P.; El-Gendy, Nashwa; Kuehl, Christopher; Berkland, Cory

    2016-01-01

    Antibiotic multi-resistant pneumonia is a risk associated with long term mechanical ventilation. Vancomycin is commonly prescribed for methicillin-resistant staphylococcus aureus infections; however, current formulations of vancomycin are only given intravenously. High doses of vancomycin have been associated with severe renal toxicity. In this study we characterized dry powder vancomyin as a potential inhaled therapeutic aerosol and compared pharmacokinetic profiles of i.v. and pulmonary administered vancomycin in intubated rabbits using a novel endotracheal tube catheter system. Cascade Impaction studies indicated that using an endotracheal tube, which bypasses deposition the mouth and throat, increased the amount of drug entering the lung. Drug deposition in the lung was further enhanced by using an endotracheal tube catheter, which did not alter the aerosol fine particle fraction. Interestingly, intubated rabbits administered 1 mg/kg vancomycin via inhalation had similar AUC to rabbits that were administered 1 mg/kg vancomycin via a single bolus i.v. infusion; however, inhalation of vancomycin reduced Cmax and increased Tmax, suggesting that inhaled vancomycin resulted in more sustained pulmonary levels of vancomycin. Collectively, these results suggested that dry powder vancomycin can successfully be delivered by pulmonary inhalation in intubated patients. Furthermore, as inhaled vancomycin is delivered locally to the site of pulmonary infection, this delivery route could reduce the total dose required for therapeutic efficacy and simultaneously reduce the risk of renal toxicity by eliminating the high levels of systemic drug exposure required to push the pulmonary dose to therapeutic thresholds during i.v. administration. PMID:25915095

  14. Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications

    PubMed Central

    Labiris, N R; Dolovich, M B

    2003-01-01

    Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally. PMID:14616419

  15. Induction of mucosal and systemic antibody responses against the HIV coreceptor CCR5 upon intramuscular immunization and aerosol delivery of a Virus-like Particle based vaccine

    PubMed Central

    Hunter, Z; Smyth, HD; Durfee, P; Chackerian, B

    2009-01-01

    Virus-like particles (VLPs) can be exploited as platforms to increase the immunogenicity of poorly immunogenic antigens, including self-proteins. We have developed VLP-based vaccines that target two domains of the HIV coreceptor CCR5 that are involved in HIV binding. These vaccines induce anti-CCR5 antibodies that bind to native CCR5 and inhibit SIV infection in vitro. Given the role of mucosal surfaces in HIV transmission and replication, we also asked whether an aerosolized, VLP-based pulmonary vaccine targeting CCR5 could induce a robust mucosal response in addition to a systemic response. In rats, both intramuscular and pulmonary immunization induced high titer IgG and IgA against the vaccine in the serum, but only aerosol vaccination induced IgA antibodies at local mucosal sites. An intramuscular prime followed by an aerosol boost resulted in strong serum and mucosal antibody responses. These results show that VLP-based vaccines targeting CCR5 induce high-titer systemic antibodies, and can elicit both local and systemic mucosal response when administered via an aerosol. Vaccination against a self-molecule that is critically involved during HIV transmission and pathogenesis is an alternative to targeting the virus itself. More generally, our results provide a general method for inducing broad systemic and mucosal antibody responses using VLP-based immunogens. PMID:19849995

  16. Pulmonary Delivery of Vancomycin Dry Powder Aerosol to Intubated Rabbits.

    PubMed

    Sullivan, Bradley P; El-Gendy, Nashwa; Kuehl, Christopher; Berkland, Cory

    2015-08-01

    Antibiotic multiresistant pneumonia is a risk associated with long-term mechanical ventilation. Vancomycin is commonly prescribed for methicillin-resistant Staphylococcus aureus infections; however, current formulations of vancomycin are only given intravenously. High doses of vancomycin have been associated with severe renal toxicity. In this study, we characterized dry powder vancomyin as a potential inhaled therapeutic aerosol and compared pharmacokinetic profiles of iv and pulmonary administered vancomycin in intubated rabbits through an endotracheal tube system. Cascade impaction studies indicated that using an endotracheal tube, which bypasses deposition in the mouth and throat, increased the amount of drug entering the lung. Bypassing the endotracheal tube with a catheter further enhanced drug deposition in the lung. Interestingly, intubated rabbits administered 1 mg/kg vancomycin via inhalation had similar AUC to rabbits that were administered 1 mg/kg vancomycin via a single bolus iv infusion; however, inhalation of vancomycin reduced Cmax and increased Tmax, indicating that inhaled vancomycin resulted in more sustained pulmonary levels of vancomycin. Collectively, these results suggested that dry powder vancomycin can successfully be delivered by pulmonary inhalation in intubated patients. Furthermore, as inhaled vancomycin is delivered locally to the site of pulmonary infection, this delivery route could reduce the total dose required for therapeutic efficacy and simultaneously reduce the risk of renal toxicity by eliminating the high levels of systemic drug exposure required to push the pulmonary dose to therapeutic thresholds during iv administration. PMID:25915095

  17. Aerosol Observing System (AOS) Handbook

    SciTech Connect

    Jefferson, A

    2011-01-17

    The Aerosol Observing System (AOS) is a suite of in situ surface measurements of aerosol optical and cloud-forming properties. The instruments measure aerosol properties that influence the earth’s radiative balance. The primary optical measurements are those of the aerosol scattering and absorption coefficients as a function of particle size and radiation wavelength and cloud condensation nuclei (CCN) measurements as a function of percent supersaturation. Additional measurements include those of the particle number concentration and scattering hygroscopic growth. Aerosol optical measurements are useful for calculating parameters used in radiative forcing calculations such as the aerosol single-scattering albedo, asymmetry parameter, mass scattering efficiency, and hygroscopic growth. CCN measurements are important in cloud microphysical models to predict droplet formation.

  18. INDUCED SPUTUM DERIVES FROM THE CENTRAL AIRWAYS: CONFIRMATION USING A RADIOLABELED AEROSOL BOLUS DELIVERY TECHNIQUE

    EPA Science Inventory

    Indirect evidence suggests that induced sputum derives from the surfaces of the bronchial airways. To confirm this experimentally, we employed a radiolabeled aerosol bolus delivery technique that preferentially deposits aerosol in the central airways in humans. We hypothesized th...

  19. Convective flow dominates aerosol delivery to the lung segments

    PubMed Central

    van Ertbruggen, C.; Prisk, G. K.

    2011-01-01

    Most previous computational studies on aerosol transport in models of the central airways of the human lung have focused on deposition, rather than transport of particles through these airways to the subtended lung regions. Using a model of the bronchial tree extending from the trachea to the segmental bronchi (J Appl Physiol 98: 970–980, 2005), we predicted aerosol delivery to the lung segments. Transport of 0.5- to 10-μm-diameter particles was computed at various gravity levels (0–1.6 G) during steady inspiration (100–500 ml/s). For each condition, the normalized aerosol distribution among the lung segments was compared with the normalized flow distribution by calculating the ratio (Ri) of the number of particles exiting each segmental bronchus i to the flow. When Ri = 1, particle transport was directly proportional to segmental flow. Flow and particle characteristics were represented by the Stokes number (Stk) in the trachea. For Stk < 0.01, Ri values were close to 1 and were unaffected by gravity. For Stk > 0.01, Ri varied greatly among the different outlets (Ri = 0.30–1.93 in normal gravity for 10-μm particles at 500 ml/s) and was affected by gravity and inertia. These data suggest that, for Stk < 0.01, ventilation defines the delivery of aerosol to lung segments and that the use of aerosol tracers is a valid technique to visualize ventilation in different parts of the lung. At higher Stokes numbers, inertia, but not gravitational sedimentation, is the second major factor affecting the transport of large particles in the lung. PMID:21474695

  20. Technological Delivery Systems.

    ERIC Educational Resources Information Center

    Kennedy, Don; And Others

    A section on technological delivery systems, presented as part of the second Australian National Workshop on Distance Education (Perth, 1983), contains four papers on using technological resources to provide educational services to persons in isolated locations. The first paper, by Don Kennedy, covers the use of satellite broadcasting of course…

  1. Terplex Gene Delivery System.

    PubMed

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16243067

  2. Terplex gene delivery system.

    PubMed

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16240997

  3. Novel antigen delivery systems.

    PubMed

    Trovato, Maria; De Berardinis, Piergiuseppe

    2015-08-12

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

  4. Aerosol Climate Interactions in Climate System Models

    NASA Astrophysics Data System (ADS)

    Kiehl, J. T.

    2002-12-01

    Aerosols are widely recognized as an important process in Earth's climate system. Observations over the past decade have improved our understanding of the physical and chemical properties of aerosols. Recently, field observations have highlighted the pervasiveness of absorbing aerosols in the atmosphere. These aerosols are of particular interest, since they alter the vertical distribution of shortwave radiative heating between the surface and atmosphere. Given this increased knowledge of aerosols from various field programs, interest is focusing on how to integrate this understanding into global climate models. These types of models provide the best tool available to comprehensively study the potential effects of aerosols on Earth's climate system. Results from climate system model simulations that include aerosol effects will be presented to illustrate key aerosol climate interactions. These simulations employ idealized and realistic distributions of absorbing aerosols. The idealized aerosol simulations provide insight into the role of aerosol shortwave absorption on the global hydrologic cycle. The realistic aerosol distributions provide insight into the local response of aerosol forcing in the Indian subcontinent region. Emphasis from these simulations will be on the hydrologic cycle, since water availability is of emerging global environmental concern. This presentation will also consider what more is needed to significantly improve our ability to model aerosol processes in climate system models. Uncertainty in aerosol climate interactions remains a major source of uncertainty in our ability to project future climate change. Focus will be on interactions between aerosols and various physical, chemical and biogeochemical aspects of the Earth system.

  5. Continuing Professional Education Delivery Systems.

    ERIC Educational Resources Information Center

    Weeks, James P.

    This investigation of delivery systems for continuing professional education provides an overview of current operational delivery systems in continuing professional education, drawing on experience as found in the literature. Learning theories and conclusions are woven into the descriptive text. Delivery systems profiled in the paper include the…

  6. Synthesis of Poly(N-isopropylacrylamide) Microcapsules for Drug Delivery Applications via UV Aerosol Photopolymerization

    NASA Astrophysics Data System (ADS)

    Roberson, Nicole; Denmark, Daniel; Witanachchi, Sarath

    Hybrid drug delivery systems composed of thermoresponsive polymers and magnetic nanoparticles have been developed using chemical methods to deliver controlled amounts of a biotherapeutic to target tissue. These methods can be expensive, time intensive, and produce impure composites due to the use of surfactants during polymer synthesis. In this study, UV aerosol photopolymerization is used to synthesize N-isoplopylacrylamide (NIPAM) monomers, N,N-methylenebisacrylamide (MBA) crosslinker, and irgacure 2959 photoinitiator into the transporting microcapsule for drug delivery. The method of UV aerosol photopolymerization allows for the continuous, cost effective, and time efficient synthesis of a high concentration of pure polymers in a short amount of time; toxic surfactants are not necessary. Optimal NIPAM monomer, MBA crosslinker, and irgacure 2959 photoinitiator concentrations were tested and analyzed to synthesize a microcapsule with optimal conditions for controlled drug delivery. Scanning Electron Microscope (SEM) imaging reveals that synthesis of polymer microcapsules of about 30 micrometers in size is effective through UV aerosol photopolymerization. Findings will contribute greatly to the field of emergency medicine. This work was supported by the United States Army (Grant No. W81XWH1020101/3349).

  7. Mucoadhesive drug delivery systems

    PubMed Central

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

    2011-01-01

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

  8. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. PMID:25703045

  9. Nanovehicular intracellular delivery systems.

    PubMed

    Prokop, Ales; Davidson, Jeffrey M

    2008-09-01

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

  10. Nanovehicular Intracellular Delivery Systems

    PubMed Central

    PROKOP, ALES; DAVIDSON, JEFFREY M.

    2013-01-01

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

  11. Transmembrane heme delivery systems

    PubMed Central

    Goldman, Barry S.; Beck, David L.; Monika, Elizabeth M.; Kranz, Robert G.

    1998-01-01

    Heme proteins play pivotal roles in a wealth of biological processes. Despite this, the molecular mechanisms by which heme traverses bilayer membranes for use in biosynthetic reactions are unknown. The biosynthesis of c-type cytochromes requires that heme is transported to the bacterial periplasm or mitochondrial intermembrane space where it is covalently ligated to two reduced cysteinyl residues of the apocytochrome. Results herein suggest that a family of integral membrane proteins in prokaryotes, protozoans, and plants act as transmembrane heme delivery systems for the biogenesis of c-type cytochromes. The complete topology of a representative from each of the three subfamilies was experimentally determined. Key histidinyl residues and a conserved tryptophan-rich region (designated the WWD domain) are positioned at the site of cytochrome c assembly for all three subfamilies. These histidinyl residues were shown to be essential for function in one of the subfamilies, an ABC transporter encoded by helABCD. We believe that a directed heme delivery pathway is vital for the synthesis of cytochromes c, whereby heme iron is protected from oxidation via ligation to histidinyl residues within the delivery proteins. PMID:9560218

  12. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

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

  13. Airborne Atmospheric Aerosol Measurement System

    NASA Astrophysics Data System (ADS)

    Ahn, K.; Park, Y.; Eun, H.; Lee, H.

    2015-12-01

    It is important to understand the atmospheric aerosols compositions and size distributions since they greatly affect the environment and human health. Particles in the convection layer have been a great concern in global climate changes. To understand these characteristics satellite, aircraft, and radio sonde measurement methods have usually been used. An aircraft aerosol sampling using a filter and/or impactor was the method commonly used (Jay, 2003). However, the flight speed particle sampling had some technical limitations (Hermann, 2001). Moreover, the flight legal limit, altitude, prohibited airspace, flight time, and cost was another demerit. To overcome some of these restrictions, Tethered Balloon Package System (T.B.P.S.) and Recoverable Sonde System(R.S.S.) were developed with a very light optical particle counter (OPC), impactor, and condensation particle counter (CPC). Not only does it collect and measure atmospheric aerosols depending on altitudes, but it also monitors the atmospheric conditions, temperature, humidity, wind velocity, pressure, GPS data, during the measurement (Eun, 2013). In this research, atmospheric aerosol measurement using T.B.P.S. in Ansan area is performed and the measurement results will be presented. The system can also be mounted to an unmanned aerial vehicle (UAV) and create an aerial particle concentration map. Finally, we will present measurement data using Tethered Balloon Package System (T.B.P.S.) and R.S.S (Recoverable Sonde System).

  14. Secondary fuel delivery system

    DOEpatents

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

    2010-02-23

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

  15. Aerosol delivery of liposome-encapsulated ciprofloxacin: aerosol characterization and efficacy against Francisella tularensis infection in mice.

    PubMed

    Conley, J; Yang, H; Wilson, T; Blasetti, K; Di Ninno, V; Schnell, G; Wong, J P

    1997-06-01

    The aerosol delivery of liposome-encapsulated ciprofloxacin by using 12 commercially available jet nebulizers was evaluated in this study. Aerosol particles containing liposome-encapsulated ciprofloxacin generated by the nebulizers were analyzed with a laser aerodynamic particle sizer. Mean mass aerodynamic diameters (MMADs) and geometric standard deviations (GSDs) were determined, and the drug contents of the sampling filters from each run onto which aerosolized liposome-encapsulated ciprofloxacin had been deposited were analyzed spectrophotometrically. The aerosol particles of liposome-encapsulated ciprofloxacin generated by these nebulizers ranged from 1.94 to 3.5 microm, with GSDs ranging from 1.51 to 1.84 microm. The drug contents of the sampling filters exposed for 1 min to aerosolized liposome-encapsulated ciprofloxacin range from 12.7 to 40.5 microg/ml (0.06 to 0.2 mg/filter). By using the nebulizer selected on the basis of most desirable MMADs, particle counts, and drug deposition, aerosolized liposome-encapsulated ciprofloxacin was used for the treatment of mice infected with 10 times the 50% lethal dose of Francisella tularensis. All mice treated with aerosolized liposome-encapsulated ciprofloxacin survived the infection, while all ciprofloxacin-treated or untreated control mice succumbed to the infection (P < 0.001). These results suggest that aerosol delivery of liposome-encapsulated ciprofloxacin to the lower respiratory tract is feasible and that it may provide an effective therapy for the treatment of respiratory tract infections. PMID:9174185

  16. High-Efficiency Generation and Delivery of Aerosols Through Nasal Cannula During Noninvasive Ventilation

    PubMed Central

    Walenga, Ross L.; Son, Yoen-Ju; Hindle, Michael

    2013-01-01

    Abstract Background Previous studies have demonstrated the delivery of pharmaceutical aerosols through nasal cannula and the feasibility of enhanced condensational growth (ECG) with a nasal interface. The objectives of this study were to develop a device for generating submicrometer aerosols with minimal depositional loss in the formation process and to improve aerosol delivery efficiencies through nasal cannulas. Methods A combination of in vitro experiments and computational fluid dynamics (CFD) simulations that used the strengths of each method was applied. Aerosols were formed using a conventional mesh nebulizer, mixed with ventilation gas, and heated to produce submicrometer sizes. An improved version of the mixer and heater unit was developed based on CFD simulations, and performance was verified with experiments. Aerosol delivery was considered through a commercial large-bore adult cannula, a divided (D) design for use with ECG, and a divided and streamlined (DS) design. Results The improved mixer design reduced the total deposition fraction (DF) of drug within the mixer by a factor of 3 compared with an initial version, had a total DF of approximately 10%, and produced submicrometer aerosols at flow rates of 10 and 15 L/min. Compared with the commercial and D designs for submicrometer aerosols, the DS cannula reduced depositional losses by a factor of 2–3 and retained only approximately 5% or less of the nebulized dose at all flow rates considered. For conventional-sized aerosols (3.9 and 4.7 μm), the DS device provided delivery efficiencies of approximately 80% and above at flow rates of 2–15 L/min. Conclusions Submicrometer aerosols can be formed using a conventional mesh nebulizer and delivered through a nasal cannula with total delivery efficiencies of 80–90%. Streamlining the nasal cannula significantly improved the delivery efficiency of both submicrometer and micrometer aerosols; however, use of submicrometer particles with ECG delivery

  17. Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization

    PubMed Central

    2014-01-01

    Background Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization. Methods In vitro structural analysis followed by in vivo protein expression studies served in assessing the integrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunization trials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutinin H1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinations using pDNA for influenza was nebulized and delivered via a respirator to sheep. Results The SAW nebulizer was effective at generating pDNA aerosols with sizes optimal for deep lung delivery. Successful gene expression was observed in mouse lung epithelial cells, when SAW-nebulized pDNA was delivered to male Swiss mice via intratracheal instillation. Effective systemic and mucosal antibody responses were found in rats via post-nebulized, condensed fluid instillation. Significantly, we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNA encoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation. Conclusion Given the difficulty of inducing functional antibody responses for DNA vaccination in large animals, we report here the first instance of successful aerosolized inhalation delivery of a pDNA vaccine in a large animal model relevant to human lung development, structure, physiology, and disease, using a novel, low-power (<1 W) surface acoustic wave (SAW) hand-held nebulizer to produce droplets of p

  18. Aerosol Measurement and Processing System (AMAPS)

    Atmospheric Science Data Center

    2016-03-22

    Description:  Access aerosol data from MISR and MODIS Subset Level-2 MISR granules by parameter and by space/time region Extract MISR aerosol data for overflights of specific geographic regions or ground site ... or concerns. Details:  Aerosol Measurement and Processing System (AMAPS) Screenshot:  ...

  19. In Vitro Evaluation of a Device for Intra-Pulmonary Aerosol Generation and Delivery

    PubMed Central

    Syedain, Zeeshan H.; Naqwi, Amir A.; Dolovich, Myrna; Somani, Arif

    2015-01-01

    For infants born with respiratory distress syndrome (RDS), liquid bolus delivery of surfactant administered through an endotracheal tube is common practice. While this method is generally effective, complications such as transient hypoxia, hypercapnia, and altered cerebral blood flow may occur. Aerosolized surfactant therapy has been explored as an alternative. Unfortunately, past efforts have led to disappointing results as aerosols were generated outside the lungs with significant pharyngeal deposition and minimal intrapulmonary instillation. A novel aerosol generator (Microjet™) is evaluated herein for intrapulmonary aerosol generation within an endotracheal tube and tested with Curosurf and Infasurf surfactants. Compared with other aerosol delivery devices, this process utilizes low air flow (range 0.01-0.2 L/min) that is ideal for limiting potential barotrauma to the premature newborn lung. The mass mean diameter (MMD) of the particles for both tested surfactants was less than 4 μm, which is ideal for both uniform and distal lung delivery. As an indicator of phospholipid function, surfactant surface tension was measured before and after aerosol formation; with no significant difference. Moreover, this device has an outside diameter of <1mm, which permits insertion into an endotracheal tube (of even 2.0 mm). In the premature infant where intravenous access is either technically challenging or difficult, aerosol drug delivery may provide an alternative route in patient resuscitation, stabilization and care. Other potential applications of this type of device include the delivery of nutrients, antibiotics, and analgesics via the pulmonary route. PMID:26884641

  20. METHODS OF CALCULATINAG LUNG DELIVERY AND DEPOSITION OF AEROSOL PARTICLES

    EPA Science Inventory


    Lung deposition of aerosol is measured by a variety of methods. Total lung deposition can be measured by monitoring inhaled and exhaled aerosols in situ by laser photometry or by collecting the aerosols on filters. The measurements can be performed accurately for stable monod...

  1. Polymers for Drug Delivery Systems

    PubMed Central

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

    2012-01-01

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

  2. Delivery methods for LVSD systems

    NASA Astrophysics Data System (ADS)

    Kasner, James H.; Brower, Bernard V.

    2011-06-01

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

  3. Production of Inhalable Submicrometer Aerosols from Conventional Mesh Nebulizers for Improved Respiratory Drug Delivery

    PubMed Central

    Longest, P. Worth; Spence, Benjamin M.; Holbrook, Landon T.; Mossi, Karla M.; Son, Yoen-Ju; Hindle, Michael

    2012-01-01

    Submicrometer and nanoparticle aerosols may significantly improve the delivery efficiency, dissolution characteristics, and bioavailability of inhaled pharmaceuticals. The objective of this study was to explore the formation of submicrometer and nanometer aerosols from mesh nebulizers suitable for respiratory drug delivery using experiments and computational fluid dynamics (CFD) modeling. Mesh nebulizers were coupled with add-on devices to promote aerosol drying and the formation of submicrometer particles, as well as to control the inhaled aerosol temperature and relative humidity. Cascade impaction experiments were used to determine the initial mass median aerodynamic diameters of 0.1% albuterol aerosols produced by the AeroNeb commercial (4.69 μm) and lab (3.90 μm) nebulizers and to validate the CFD model in terms of droplet evaporation. Through an appropriate selection of flow rates, nebulizers, and model drug concentrations, submicrometer and nanometer aerosols could be formed with the three devices considered. Based on CFD simulations, a wire heated design was shown to overheat the airstream producing unsafe conditions for inhalation if the aerosol was not uniformly distributed in the tube cross-section or if the nebulizer stopped producing droplets. In comparison, a counter-flow heated design provided sufficient thermal energy to produce submicrometer particles, but also automatically limited the maximum aerosol outlet temperature based on the physics of heat transfer. With the counter-flow design, submicrometer aerosols were produced at flow rates of 5, 15, and 30 LPM, which may be suitable for various forms of oral and nasal aerosol delivery. Thermodynamic conditions of the aerosol stream exiting the counter-flow design were found be in a range of 21-45 °C with relative humidity greater than 40% in some cases, which was considered safe for direct inhalation and advantageous for condensational growth delivery. PMID:22707794

  4. Aerosol sampling system

    DOEpatents

    Masquelier, Donald A.

    2004-02-10

    A system for sampling air and collecting particulate of a predetermined particle size range. A low pass section has an opening of a preselected size for gathering the air but excluding particles larger than the sample particles. An impactor section is connected to the low pass section and separates the air flow into a bypass air flow that does not contain the sample particles and a product air flow that does contain the sample particles. A wetted-wall cyclone collector, connected to the impactor section, receives the product air flow and traps the sample particles in a liquid.

  5. Electronic Nicotine Delivery Systems

    PubMed Central

    Adkison, Sarah E.; O’Connor, Richard J.; Bansal-Travers, Maansi; Hyland, Andrew; Borland, Ron; Yong, Hua-Hie; Cummings, K. Michael; McNeill, Ann; Thrasher, James F.; Hammond, David; Fong, Geoffrey T.

    2013-01-01

    Background Electronic nicotine delivery systems (ENDS) initially emerged in 2003 and have since become widely available globally, particularly over the Internet. Purpose Data on ENDS usage patterns are limited. The current paper examines patterns of ENDS awareness, use, and product-associated beliefs among current and former smokers in four countries. Methods Data come from Wave 8 of the International Tobacco Control Four-Country Survey, collected July 2010 to June 2011 and analyzed through June 2012. Respondents included 5939 current and former smokers in Canada (n=1581); the U.S. (n=1520); the United Kingdom (UK; n=1325); and Australia (n=1513). Results Overall, 46.6% were aware of ENDS (U.S.: 73%, UK: 54%, Canada: 40%, Australia: 20%); 7.6% had tried ENDS (16% of those aware of ENDS); and 2.9% were current users (39% of triers). Awareness of ENDS was higher among younger, non-minority smokers with higher incomes who were heavier smokers. Prevalence of trying ENDS was higher among younger, nondaily smokers with a high income and among those who perceived ENDS as less harmful than traditional cigarettes. Current use was higher among both nondaily and heavy (≥20 cigarettes per day) smokers. In all, 79.8% reported using ENDS because they were considered less harmful than traditional cigarettes; 75.4% stated that they used ENDS to help them reduce their smoking; and 85.1% reported using ENDS to help them quit smoking. Conclusions Awareness of ENDS is high, especially in countries where they are legal (i.e., the U.S. and UK). Because trial was associated with nondaily smoking and a desire to quit smoking, ENDS may have potential to serve as a cessation aid. PMID:23415116

  6. Size effect on transfection and cytotoxicity of nanoscale plasmid DNA/polyethyleneimine complexes for aerosol gene delivery

    NASA Astrophysics Data System (ADS)

    Hoon Byeon, Jeong; Kim, Jang-Woo

    2014-02-01

    Nanoscale plasmid DNA (pDNA)/polyethyleneimine (PEI) complexes were fabricated in the aerosol state using a nebulization system consisting of a collison atomizer and a cool-walled diffusion dryer. The aerosol fabricated nanoscale complexes were collected and employed to determine fundamental properties of the complexes, such as size, structure, surface charge, and in vitro gene transfection efficiency and cytotoxicity. The results showed that mass ratio between pDNA and PEI should be optimized to enhance gene transfection efficiency without a significant loss of cell viability. These findings may support practical advancements in the field of nonviral gene delivery.

  7. Size effect on transfection and cytotoxicity of nanoscale plasmid DNA/polyethyleneimine complexes for aerosol gene delivery

    SciTech Connect

    Hoon Byeon, Jeong; Kim, Jang-Woo

    2014-02-03

    Nanoscale plasmid DNA (pDNA)/polyethyleneimine (PEI) complexes were fabricated in the aerosol state using a nebulization system consisting of a collison atomizer and a cool-walled diffusion dryer. The aerosol fabricated nanoscale complexes were collected and employed to determine fundamental properties of the complexes, such as size, structure, surface charge, and in vitro gene transfection efficiency and cytotoxicity. The results showed that mass ratio between pDNA and PEI should be optimized to enhance gene transfection efficiency without a significant loss of cell viability. These findings may support practical advancements in the field of nonviral gene delivery.

  8. Transcutaneous antigen delivery system

    PubMed Central

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

    2013-01-01

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

  9. Radiation delivery system and method

    DOEpatents

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

    2002-01-01

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

  10. The science guiding selection of an aerosol delivery device.

    PubMed

    Myers, Timothy R

    2013-11-01

    Aerosol therapy continues to be considered as one of the cornerstones of the profession of respiratory care, even after 60 years. Aerosol therapy serves as a critical intervention for both exacerbations and chronic maintenance for a variety of respiratory care conditions. Aerosol therapy uniquely blends both the art and science of medicine together to produce the practical and necessary clinical outcomes for patients with respiratory diseases. This review was presented as part of the New Horizons Symposium on how to guide the scientific selection of an appropriate aerosol device. PMID:24155355

  11. Fluid delivery control system

    SciTech Connect

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

    2006-06-06

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

  12. Pulmonary delivery of an aerosolized recombinant human butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques.

    PubMed

    Rosenberg, Yvonne J; Laube, Beth; Mao, Lingjun; Jiang, Xiaoming; Hernandez-Abanto, Segundo; Lee, Keunmyoung D; Adams, Robert

    2013-03-25

    Butyrylcholinesterase (BChE) is the leading pretreatment candidate against exposure to organophosphates (OPs), which pose an ever increasing public and military health. Since respiratory failure is the primary cause of death following acute OP poisoning, an inhaled BChE therapeutic could prove highly efficacious in preventing acute toxicity as well as the associated delayed neuropathy. To address this, studies have been performed in mice and macaques using Chinese Hamster Ovary cells (CHO)-derived recombinant (r) BChE delivered by the pulmonary route, to examine whether the deposition of both macaque (Ma) and human (Hu) rBChE administered as aerosols (aer) favored the creation and retention of an efficient protective "pulmonary bioshield" that could scavenge incoming (inhaled) OPs in situ thereby preventing entry into the circulation and inhibition of plasma BChE and AChE on red blood cells (RBC-AChE) and in cholinergic synapses. In contrast to parenteral delivery of rBChE, which currently requires posttranslational modification for good plasma stability, an unmodified aer-rBChE pretreatment given 1-40 h prior to >1 LD50 of aer-paraoxon (Px) was able to prevent inhibition of circulating cholinesterase in a dose-dependent manner. These studies are the first to show protection by rBChE against a pesticide such as paraoxon when delivered directly into the lung and bode well for the use of a non-invasive and consumer friendly method of rHuBChE delivery as a human treatment to counteract OP toxicity. PMID:23178380

  13. Adenosine-Associated Delivery Systems

    PubMed Central

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

    2016-01-01

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

  14. Aerosolized adenovirus-vectored vaccine as an alternative vaccine delivery method

    PubMed Central

    2011-01-01

    Conventional parenteral injection of vaccines is limited in its ability to induce locally-produced immune responses in the respiratory tract, and has logistical disadvantages in widespread vaccine administration. Recent studies suggest that intranasal delivery or vaccination in the respiratory tract with recombinant viral vectors can enhance immunogenicity and protection against respiratory diseases such as influenza and tuberculosis, and can offer more broad-based generalized protection by eliciting durable mucosal immune responses. Controlled aerosolization is a method to minimize vaccine particle size and ensure delivery to the lower respiratory tract. Here, we characterize the dynamics of aerosolization and show the effects of vaccine concentration on particle size, vector viability, and the actual delivered dose of an aerosolized adenoviral vector. In addition, we demonstrate that aerosol delivery of a recombinant adenoviral vaccine encoding H1N1 hemagglutinin is immunogenic and protects ferrets against homologous viral challenge. Overall, aerosol delivery offers comparable protection to intramuscular injection, and represents an attractive vaccine delivery method for broad-based immunization campaigns. PMID:22103776

  15. Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice.

    PubMed

    Minai-Tehrani, Arash; Park, Young-Chan; Hwang, Soon-Kyung; Kwon, Jung-Taek; Chang, Seung-Hee; Park, Sung-Jin; Yu, Kyeong-Nam; Kim, Ji-Eun; Shin, Ji-Young; Kim, Ji-Hye; Kang, Bitna; Hong, Seong-Ho; Cho, Myung-Haing

    2011-12-01

    Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery. PMID:22122896

  16. Development of insulin delivery systems.

    PubMed

    Siddiqui, N I; Siddiqui, Ni; Rahman, S; Nessa, A

    2008-01-01

    Delivery system of insulin is vital for its acceptance and adherence to therapy for achieving the glycemic targets. Enormous developments have occurred in the delivery system of insulin during the last twenty years and each improvement was aimed at two common goals: patients convenience and better glycemic control. Till to date, the various insulin delivery systems are: syringes/vials, injection aids, jet injectors, transmucosal delivery, transdermal delivery, external insulin infusion pump, implantable insulin pumps, insulin pens and insulin inhalers. Syringe/vial is the oldest and conventional method, still widely used and relatively cheaper. Modern plastic syringes are disposable, light weight with microfine needle for patients convenience and comfort. Oral route could be the most acceptable and viable, if the barriers can be overcome and under extensive trial. Insulin pen device is an important milestone in the delivery system of insulin as it is convenient, discrete, painless, attractive, portable with flexible life style and improved quality of life. More than 80% of European diabetic patients are using insulin pen. Future digital pen will have better memory option, blood glucose monitoring system, insulin dose calculator etc. Insulin infusion pump is a good option for the children, busy patients with flexible lifestyle and those who want to avoid multiple daily injections. Pulmonary route of insulin delivery is a promising, effective, non-invasive and acceptable alternative method. Exubera, the world first insulin inhaler was approved by FDA in 28 January 2006. But due to certain limitations, it has been withdrawn from the market in October 2007. The main concern of inhaled insulin are: long term pulmonary safety issues, cost effectiveness and user friendly device. In future, more acceptable and cost effective insulin inhaler will be introduced. Newer avenues are under extensive trial for better future insulin delivery systems. PMID:18285745

  17. Nanoparticulate systems for polynucleotide delivery

    PubMed Central

    Basarkar, Ashwin; Singh, Jagdish

    2007-01-01

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

  18. Photochemistry of Model Organic Aerosol Systems

    NASA Astrophysics Data System (ADS)

    Mang, S. A.; Bateman, A. P.; Dailo, M.; Do, T.; Nizkorodov, S. A.; Pan, X.; Underwood, J. S.; Walser, M. L.

    2007-05-01

    Up to 90 percent of urban aerosol particles have been shown to contain organic molecules. Reactions of these particles with atmospheric oxidants and/or sunlight result in large changes in their composition, toxicity, and ability to act as cloud condensation nuclei. For this reason, chemistry of model organic aerosol particles initiated by oxidation and direct photolysis is of great interest to atmospheric, climate, and health scientists. Most studies in this area have focused on identifying the products of oxidation of the organic aerosols, while the products of direct photolysis of the resulting molecules remaining in the aerosol particle have been left mostly unexplored. We have explored direct photolytic processes occurring in selected organic aerosol systems using infrared cavity ringdown spectroscopy to identify small gas phase products of photolysis, and mass-spectrometric and photometric techniques to study the condensed phase products. The first model system was secondary organic aerosol formed from the oxidation of several monoterpenes by ozone in the presence and absence of NOx, under different humidities. The second system modeled after oxidatively aged primary organic aerosol particles was a thin film of either alkanes or saturated fatty acids oxidized in several different ways, with the oxidation initiated by ozone, chlorine atom, or OH. In every case, the general conclusion was that the photochemical processing of model organic aerosols is significant. Such direct photolysis processes are believed to age organic aerosol particles on time scales that are short compared to the particles' atmospheric lifetimes.

  19. Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler

    PubMed Central

    Golshahi, Laleh; Behara, Srinivas R.B.; Tian, Geng; Farkas, Dale R.; Hindle, Michael

    2015-01-01

    Abstract Purpose: Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy. Methods: The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region. Results: The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5–2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%. Conclusions: The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy. PMID:25192072

  20. Novel central nervous system drug delivery systems.

    PubMed

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

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases. PMID:24325540

  1. Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol

    PubMed Central

    Zarogoulidis, Paul; Kioumis, Ioannis; Lampaki, Sofia; Organtzis, John; Porpodis, Konstantinos; Spyratos, Dionysios; Pitsiou, Georgia; Petridis, Dimitris; Pataka, Athanasia; Huang, Haidong; Li, Qiang; Yarmus, Lonny; Hohenforst-Schmidt, Wolfgang; Pezirkianidis, Nikolaos; Zarogoulidis, Konstantinos

    2014-01-01

    Background At this time, several antibiotics have been investigated as possibilities for aerosol administration, but local therapy has been found to be more efficient in several diseases. Materials and methods The drugs linezolid (Zyvox), vancomycin (Voncon), and daptomycin (Cubicin) were tested with three jet nebulizers with seven different residual cups and different loadings. Moreover, three ultrasound nebulizers were again tested with these drugs, with different loadings and mouthpiece attachments. Results When drugs are combined with particular cup designs, they significantly lower the droplet size to 1.60 and 1.80 μm, which represents the best combination of Zyvox and cup G and Cubicin and cup D, respectively. Cup design D is suggested as the most effective cup for lowering the droplet size (2.30 μm) when considering a higher loading level (8 mL). Conclusion Modification of current drugs from dry powder to solution is possible, and the residual cup design plays the most important role in droplet size production when the nebulization systems have the same properties. PMID:25143711

  2. Multi-Sensor Aerosol Products Sampling System

    NASA Technical Reports Server (NTRS)

    Petrenko, M.; Ichoku, C.; Leptoukh, G.

    2011-01-01

    Global and local properties of atmospheric aerosols have been extensively observed and measured using both spaceborne and ground-based instruments, especially during the last decade. Unique properties retrieved by the different instruments contribute to an unprecedented availability of the most complete set of complimentary aerosol measurements ever acquired. However, some of these measurements remain underutilized, largely due to the complexities involved in analyzing them synergistically. To characterize the inconsistencies and bridge the gap that exists between the sensors, we have established a Multi-sensor Aerosol Products Sampling System (MAPSS), which consistently samples and generates the spatial statistics (mean, standard deviation, direction and rate of spatial variation, and spatial correlation coefficient) of aerosol products from multiple spacebome sensors, including MODIS (on Terra and Aqua), MISR, OMI, POLDER, CALIOP, and SeaWiFS. Samples of satellite aerosol products are extracted over Aerosol Robotic Network (AERONET) locations as well as over other locations of interest such as those with available ground-based aerosol observations. In this way, MAPSS enables a direct cross-characterization and data integration between Level-2 aerosol observations from multiple sensors. In addition, the available well-characterized co-located ground-based data provides the basis for the integrated validation of these products. This paper explains the sampling methodology and concepts used in MAPSS, and demonstrates specific examples of using MAPSS for an integrated analysis of multiple aerosol products.

  3. Aerosol delivery of antimicrobial agents during mechanical ventilation: current practice and perspectives.

    PubMed

    Michalopoulos, Argyris; Metaxas, Eugenios I; Falagas, Matthew E

    2011-03-01

    Critically ill patients, who develop ventilator-associated pneumonia during prolonged mechanical ventilation, often require antimicrobial agents administered through the endotracheal or the tracheotomy tube. The delivery of antibiotics via the respiratory tract has been established over the past years as an alternative route in order to deliver high concentrations of antimicrobial agents directly to the lungs and avoid systemic toxicity. Since the only formal indications for inhaled/aerosolized antimicrobial agents is for patients suffering from cystic fibrosis, consequently the majority of research and published studies concerns this group of patients. Newer devices and new antibiotic formulations are currently off-label used in ambulatory cystic fibrosis patients whereas similar data for the mechanically ventilated patients do not yet exist. PMID:21235473

  4. Delivery System, 2003-2004.

    ERIC Educational Resources Information Center

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

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

  5. Advances in Gene Delivery Systems

    PubMed Central

    Kamimura, Kenya; Suda, Takeshi; Zhang, Guisheng; Liu, Dexi

    2011-01-01

    The transfer of genes into cells, both in vitro and in vivo, is critical for studying gene function and conducting gene therapy. Methods that utilize viral and nonviral vectors, as well as physical approaches, have been explored. Viral vector-mediated gene transfer employs replication-deficient viruses such as retro-virus, adenovirus, adeno-associated virus and herpes simplex virus. A major advantage of viral vectors is their high gene delivery efficiency. The nonviral vectors developed so far include cationic liposomes, cationic polymers, synthetic peptides and naturally occurring compounds. These nonviral vectors appear to be highly effective in gene delivery to cultured cells in vitro but are significantly less effective in vivo. Physical methods utilize mechanical pressure, electric shock or hydrodynamic force to transiently permeate the cell membrane to transfer DNA into target cells. They are simpler than viral- and nonviral-based systems and highly effective for localized gene delivery. The past decade has seen significant efforts to establish the most desirable method for safe, effective and target-specific gene delivery, and good progress has been made. The objectives of this review are to (i) explain the rationale for the design of viral, nonviral and physical methods for gene delivery; (ii) provide a summary on recent advances in gene transfer technology; (iii) discuss advantages and disadvantages of each of the most commonly used gene delivery methods; and (iv) provide future perspectives. PMID:22200988

  6. Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy.

    PubMed

    Davies, Lee A; Nunez-Alonso, Graciela A; McLachlan, Gerry; Hyde, Stephen C; Gill, Deborah R

    2014-06-01

    Abstract Lung gene therapy is being evaluated for a range of acute and chronic diseases, including cystic fibrosis (CF). As these therapies approach clinical realization, it is becoming increasingly clear that the ability to efficiently deliver gene transfer agents (GTAs) to target cell populations within the lung may prove just as critical as the gene therapy formulation itself in terms of generating positive clinical outcomes. Key to the success of any aerosol gene therapy is the interaction between the GTA and nebulization device. We evaluated the effects of aerosolization on our preferred formulation, plasmid DNA (pDNA) complexed with the cationic liposome GL67A (pDNA/GL67A) using commercially available nebulizer devices. The relatively high viscosity (6.3±0.1 cP) and particulate nature of pDNA/GL67A formulations hindered stable aerosol generation in ultrasonic and vibrating mesh nebulizers but was not problematic in the jet nebulizers tested. Aerosol size characteristics varied significantly between devices, but the AeroEclipse II nebulizer operating at 50 psi generated stable pDNA/GL67A aerosols suitable for delivery to the CF lung (mass median aerodynamic diameter 3.4±0.1 μm). Importantly, biological function of pDNA/GL67A formulations was retained after nebulization, and although aerosol delivery rate was lower than that of other devices (0.17±0.01 ml/min), the breath-actuated AeroEclipse II nebulizer generated aerosol only during the inspiratory phase and as such was more efficient than other devices with 83±3% of generated aerosol available for patient inhalation. On the basis of these results, we have selected the AeroEclipse II nebulizer for the delivery of pDNA/GL67A formulations to the lungs of CF patients as part of phase IIa/b clinical studies. PMID:24865497

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

    PubMed

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

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery. PMID:23662604

  8. Special Delivery Systems. Final Report.

    ERIC Educational Resources Information Center

    Molek, Carol

    The Special Delivery Systems project developed a curriculum for students with learning disabilities (LD) in an adult basic education program. The curriculum was designed to assist and motivate the students in the educational process. Fourteen students with LD were recruited and screened. The curriculum addressed varied learning styles combined…

  9. Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy.

    PubMed

    Davies, Lee Adrian; Nunez-Alonso, Graciela A; McLachlan, Gerry; Hyde, Stephen C; Gill, Deborah Rebecca

    2014-04-29

    Lung gene therapy is being evaluated for a range of acute and chronic diseases including cystic fibrosis (CF). As these therapies approach clinical realisation it is becoming increasingly clear that the ability to efficiently deliver gene transfer agents (GTAs) to target cell populations within the lung may prove just as critical as the gene therapy formulation itself in terms of generating positive clinical outcomes. Key to the success of any aerosol gene therapy is the interaction between the GTA and nebulisation device. We evaluated the effects of aerosolisation on our preferred formulation, plasmid DNA (pDNA) complexed with the cationic liposome GL67A (pDNA/GL67A) using commercially available nebuliser devices. The relatively high viscosity (6.3 ± 0.1 cP) and particulate nature of pDNA/GL67A formulations hindered stable aerosol generation in ultrasonic and vibrating mesh nebulisers, but was not problematic in the jet nebulisers tested. Aerosol size characteristics varied significantly between devices but the AeroEclipse II nebuliser operating at 50 psi generated stable pDNA/GL67A aerosols suitable for delivery to the CF lung (MMAD 3.4 ± 0.1 µm). Importantly, biological function of pDNA/GL67A formulations was retained following nebulisation and although aerosol delivery rate was lower than other devices (0.17 ± 0.01 ml/min) the breath-actuated AeroEclipse II nebuliser generated aerosol only during the inspiratory phase and as such was more efficient than other devices with 83 ± 3% of generated aerosol available for patient inhalation. Based on these results we have selected the AeroEclipse II nebuliser for the delivery of pDNA/GL67A formulations to the lungs of CF patients as part of Phase IIa/b clinical studies. PMID:24773062

  10. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

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

  11. Insulin Delivery System

    NASA Technical Reports Server (NTRS)

    1988-01-01

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

  12. Nicotine Delivery to Rats via Lung Alveolar Region-Targeted Aerosol Technology Produces Blood Pharmacokinetics Resembling Human Smoking

    PubMed Central

    2013-01-01

    Introduction: Nicotine is a heavily used addictive drug acquired through smoking tobacco. Nicotine in cigarette smoke is deposited and absorbed in the lungs, which results in a rapidly peaked slowly declining arterial concentration. This pattern plays an important role in initiation of nicotine addiction. Methods: A method and device were developed for delivering nicotine to rodents with lung alveolar region-targeted aerosol technology. The dose of delivery can be controlled by the nicotine aerosol concentration and duration of exposure. Results: Our data showed that, in the breathing zone of the nose-only exposure chamber, the aerosol droplet size distribution was within the respirable diameter range. Rats were exposed to nicotine aerosol for 2min. The arterial blood nicotine concentration reached 43.2±15.7ng/ml (mean ± SD) within 1–4min and declined over the next 20min, closely resembling the magnitude and early pharmacokinetics of a human smoking a cigarette. The acute inhalation toxicity of nicotine: LC50 = 2.3mg/L was determined; it was affected by pH, suggesting that acidification decreases nicotine absorption and/or bioavailability. Conclusions: A noninvasive method and toolkit were developed for delivering nicotine to rodents that enable rapid delivery of a controllable amount of nicotine into the systemic circulation and brain-inducing dose-dependent pharmacological effects, even a lethal dose. Aerosol inhalation can produce nicotine kinetics in both arterial and venous blood resembling human smoking. This method can be applied to studies of the effects of chronic intermittent nicotine exposure, nicotine addiction, toxicology, tobacco-related diseases, teratogenicity, and for discovery of pharmacological therapeutics. PMID:23239844

  13. Planning health care delivery systems.

    PubMed Central

    Baum, M A; Bergwall, D F; Reeves, P N

    1975-01-01

    The increasing concern and interest in the health delivery system in the United States has placed the health system planners in a difficult position. They are inadequately prepared, in many cases, to deal with the management techniques that have been designed for use with system problems. This situation has been compounded by the failure, until recently, of educational programs to train new health professionals in these techniques. Computer simulation is a technique that allows the planners dynamic feedback on his proposed plans. This same technique provides the planning student with a better understanding of the systems planning process. PMID:1115292

  14. Inhibition of experimental lung metastasis by aerosol delivery of PEI-p53 complexes.

    PubMed

    Gautam, A; Densmore, C L; Waldrep, J C

    2000-10-01

    Mutations in the p53 tumor suppressor gene and the pathways mediated by the p53 protein are common in many human cancers. Replacement of functional p53 by gene therapy is a potential way of combating these cancers and the associated drug resistance and tumor growth. Aerosol delivery of genes is a noninvasive way of targeting genes to the lung for gene therapy. Here we demonstrate, using a murine melanoma lung metastasis model, that aerosol delivery of polyethyleneimine-p53 (PEI-p53) complexes inhibits the growth of lung metastasis. A significantly reduced number of visible foci were observed in C57BL/6 mice injected with B16-F10 melanoma and treated with PEI-p53 complexes by aerosol for 3 weeks at twice a week. Fifty percent of the mice in the PEI-p53-treated group exhibited no visible tumor foci. There was a significant reduction in the lung weights of p53-treated mice (P < 0.01) compared to control groups. The tumor burden was also significantly lower (P < 0.001) in mice treated with PEI-p53 complexes. No extrapulmonary metastasis was observed in the groups treated with PEI-p53 complexes compared to 50% of the mice in control groups, which showed metastasis to lymph nodes in the neck or abdomen. Treatment with PEI-p53 aerosol also led to about a 50% increase in the mean length of survival of the mice injected with B16-F10 cells. These data suggest that delivery of the p53 gene by aerosol using PEI as the gene delivery vector can inhibit the growth of lung metastasis. PMID:11020346

  15. Mucoadhesive vaginal drug delivery systems.

    PubMed

    Acartürk, Füsun

    2009-11-01

    Vaginal delivery is an important route of drug administration for both local and systemic diseases. The vaginal route has some advantages due to its large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to many drugs and self-insertion. The traditional commercial preparations, such as creams, foams, gels, irrigations and tablets, are known to reside in the vaginal cavity for a relatively short period of time owing to the self-cleaning action of the vaginal tract, and often require multiple daily doses to ensure the desired therapeutic effect. The vaginal route appears to be highly appropriate for bioadhesive drug delivery systems in order to retain drugs for treating largely local conditions, or for use in contraception. In particular, protection against sexually-transmitted diseases is critical. To prolong the residence time in the vaginal cavity, bioadhesive therapeutic systems have been developed in the form of semi-solid and solid dosage forms. The most commonly used mucoadhesive polymers that are capable of forming hydrogels are synthetic polyacrylates, polycarbophil, chitosan, cellulose derivatives (hydroxyethycellulose, hydroxy-propylcellulose and hydroxypropylmethylcellulose), hyaluronic acid derivatives, pectin, tragacanth, carrageenan and sodium alginate. The present article is a comprehensive review of the patents related to mucoadhesive vaginal drug delivery systems. PMID:19925443

  16. Topical Drug Delivery in Chronic Rhinosinusitis Patients before and after Sinus Surgery Using Pulsating Aerosols

    PubMed Central

    Möller, Winfried; Schuschnig, Uwe; Celik, Gülnaz; Münzing, Wolfgang; Bartenstein, Peter; Häussinger, Karl; Kreyling, Wolfgang G.; Knoch, Martin

    2013-01-01

    Objectives Chronic rhinosinusitis (CRS) is a common chronic disease of the upper airways and has considerable impact on quality of life. Topical delivery of drugs to the paranasal sinuses is challenging, therefore the rate of surgery is high. This study investigates the delivery efficiency of a pulsating aerosol in comparison to a nasal pump spray to the sinuses and the nose in healthy volunteers and in CRS patients before and after sinus surgery. Methods 99mTc-DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal polyps before and after sinus surgery. In addition, pulsating aerosols were studied in comparison to nasal pump sprays in eleven healthy volunteers. Total nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung penetration were assessed by anterior and lateral planar gamma camera imaging. Results In healthy volunteers nasal pump sprays resulted in 100% nasal, non-significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/-8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in healthy volunteers nor in CRS patients there was significant dose in the frontal sinuses. Conclusion In contrast to nasal pump sprays, pulsating aerosols can deliver significant doses into posterior nasal spaces and paranasal sinuses, providing alternative therapy options before and after sinus surgery. Patients with chronic lung diseases based on clearance dysfunction may also benefit from pulsating aerosols, since these diseases also manifest in the upper airways. PMID:24040372

  17. 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

  18. Numerical investigation of aerosolized drug delivery in the human lungs under mechanical ventilator conditions

    NASA Astrophysics Data System (ADS)

    Vanrhein, Timothy; Banerjee, Arindam

    2010-11-01

    Particle deposition for aerosolized drug delivery in the human airways is heavily dependent upon flow conditions. Numerical modeling techniques have proven valuable for determining particle deposition characteristics under steady flow conditions. For the case of patients under mechanical ventilation, however, flow conditions change drastically and there is an increased importance to understand particle deposition characteristics. This study focuses on mechanically ventilated conditions in the upper trachea-bronchial (TB) region of the human airways. Solution of the continuous phase flow is done under ventilator waveform conditions with a suitable turbulence model in conjunction with a realistic model of upper TB airways. A discrete phase Euler-Lagrange approach is applied to solve for particle deposition characteristics with a focus on the effect of the ventilator inlet waveform. The purpose of this study is to accurately model flow conditions in the upper TB airways under mechanically ventilated conditions with a focus on real-time patient specific targeted aerosolized drug delivery.

  19. The Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) in vitro system: design and experimental protocol.

    PubMed

    Hein, Stephanie; Bur, Michael; Kolb, Tobias; Muellinger, Bernhard; Schaefer, Ulrich F; Lehr, Claus-Michael

    2010-08-01

    The development of aerosol medicines typically involves numerous tests on animals, due to the lack of adequate in vitro models. A new in vitro method for testing pharmaceutical aerosol formulations on cell cultures was developed, consisting of an aerosolisation unit fitting a commercial dry powder inhaler (HandiHaler(c), Boehringer Ingelheim, Germany), an air-flow control unit (Akita(c), Activaero, Germany) and a custom-made sedimentation chamber. This chamber holds three Snapwell(c) inserts with monolayers of pulmonary epithelial cells. The whole set-up, referred to as the Pharmaceutical Aerosol Deposition Device On Cell Cultures (PADDOCC) system, aims to mimic the complete process of aerosol drug delivery, encompassing aerosol generation, aerosol deposition onto pulmonary epithelial cells and subsequent drug transport across this biological barrier, to facilitate the investigation of new aerosol formulations in the early stages of development. We describe here, the development of the design and the protocol for this device. By testing aerosol formulations of budesonide and salbutamol sulphate, respectively, reproducible deposition of aerosol particles on, and the integrity of, the pulmonary cell monolayer could be demonstrated. PMID:20822321

  20. Effect of ethanol on droplet size, efficiency of delivery, and clearance characteristics of technetium-99m DTPA aerosol.

    PubMed

    Sirr, S A; Juenemann, P J; Tom, H; Boudreau, R J; Chandler, R P; Loken, M K

    1985-06-01

    With recent technical advances in aerosol technology, the study of regional ventilation using [99mTc]DTPA aerosol has become increasingly popular. Using a cascade impactor, we have assessed droplet size distribution from a newly designed nebulizer. Delivery efficiency of [99mTc]DTPA aerosol to normal subjects was improved 70% with a 10% concentration of ethanol in the nebulizer. Using filter paper fixed to the delivery end of the aerosol device, and varying ethanol concentrations from 0-10%, an 87% increase of deposited radioactivity is measured. Use of higher concentration of ethanol to the nebulizer solution did not further improve delivery efficiency. The addition of ethanol did not alter clearance characteristics of [99mTc]DTPA from the lung nor did it affect droplet size distribution. PMID:3889235

  1. Radiological/biological/aerosol removal system

    DOEpatents

    Haslam, Jeffery J

    2015-03-17

    An air filter replacement system for existing buildings, vehicles, arenas, and other enclosed airspaces includes a replacement air filter for replacing a standard air filter. The replacement air filter has dimensions and air flow specifications that allow it to replace the standard air filter. The replacement air filter includes a filter material that removes radiological or biological or aerosol particles.

  2. Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery

    PubMed Central

    Duan, Jinghua; Vogt, Frederick G; Li, Xiaojian; Hayes, Don; Mansour, Heidi M

    2013-01-01

    The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders. PMID:24092972

  3. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-04-01

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

  4. A satellite view of aerosols in the climate system

    NASA Technical Reports Server (NTRS)

    Kaufman, Yoram J.; Tanre, Didier; Boucher, Olivier

    2002-01-01

    Anthropogenic aerosols are intricately linked to the climate system and to the hydrologic cycle. The net effect of aerosols is to cool the climate system by reflecting sunlight. Depending on their composition, aerosols can also absorb sunlight in the atmosphere, further cooling the surface but warming the atmosphere in the process. These effects of aerosols on the temperature profile, along with the role of aerosols as cloud condensation nuclei, impact the hydrologic cycle, through changes in cloud cover, cloud properties and precipitation. Unravelling these feedbacks is particularly difficult because aerosols take a multitude of shapes and forms, ranging from desert dust to urban pollution, and because aerosol concentrations vary strongly over time and space. To accurately study aerosol distribution and composition therefore requires continuous observations from satellites, networks of ground-based instruments and dedicated field experiments. Increases in aerosol concentration and changes in their composition, driven by industrialization and an expanding population, may adversely affect the Earth's climate and water supply.

  5. Integrated delivery systems. Evolving oligopolies.

    PubMed

    Malone, T A

    1998-01-01

    The proliferation of Integrated Delivery Systems (IDSs) in regional health care markets has resulted in the movement of these markets from a monopolistic competitive model of behavior to an oligopoly. An oligopoly is synonymous with competition among the few, as a small number of firms supply a dominant share of an industry's total output. The basic characteristics of a market with competition among the few are: (1) A mutual interdependence among the actions and behaviors of competing firms; (2) competition tends to rely on the differentiation of products; (3) significant barriers to entering the market exist; (4) the demand curve for services may be kinked; and (5) firms can benefit from economies of scale. An understanding of these characteristics is essential to the survival of IDSs as regional managed care markets mature. PMID:10180497

  6. Microfabricated injectable drug delivery system

    DOEpatents

    Krulevitch, Peter A.; Wang, Amy W.

    2002-01-01

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

  7. Enhanced transdermal delivery of sex hormones in swine with a novel topical aerosol.

    PubMed

    Morgan, T M; Parr, R A; Reed, B L; Finnin, B C

    1998-10-01

    This study investigated the enhanced transdermal delivery of testosterone (Tes) and estradiol (E2) in swine in vivo with novel metered-dose topical aerosols containing the penetration enhancer padimate O (PadO) and predicted the dose deliverable in humans from the calculated drug flux across the skin. Weanling swine were catheterized and castrated under general anaesthesia and used as a conscious hypogonadal model. Tes and E2 (with and without PadO) were applied once, and venous blood samples were taken over 24 h. Tes and E2 plasma levels were determined by radioimmunoassay. After daily topical dosing of Tes for 6 days, the plasma Tes levels were determined and the transdermal flux was calculated by correcting the pseudo steady-state plasma concentration versus time profile with the clearance of an iv dose within the same swine. After a single application of the E2 aerosol over 30 cm2, or the Tes aerosol over 180 cm2, the mean AUC0-24 h when PadO was included in the spray was 14.1- and 2.0-fold greater than control, respectively (p < 0.03). After the sixth application of the Tes spray with PadO, the mean flux (+/-SE, n = 4) across swine skin in vivo was 2.12 +/- 0.35 microg/cm2.h, which gave a predicted flux in humans of 0.95 microg/cm2.h. From these data the expected plasma levels of Tes in hypogonadal men would compare well with the normal diurnal Tes profile in healthy men. These novel topical aerosols are capable of enhanced transdermal delivery of sex hormones in vivo, and they have the potential to deliver clinically relevant doses to humans. PMID:9758680

  8. Physically facilitating drug-delivery systems

    PubMed Central

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

    2012-01-01

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

  9. Fiber coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan

    2008-08-12

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

  10. Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

    PubMed Central

    Wu, Xiao; Zhang, Weifen; Hayes, Don; Mansour, Heidi M

    2013-01-01

    In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug – cyclosporine A – for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero- 3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters. PMID:23569375

  11. Development of the Choctaw Health Delivery System.

    ERIC Educational Resources Information Center

    Nguyen, Binh N.

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

  12. Gastroretentive delivery systems: hollow beads.

    PubMed

    Talukder, R; Fassihi, R

    2004-04-01

    The objective of this study was to develop a floatable multiparticulate system with potential for intragastric sustained drug delivery. Cross-linked beads were made by using calcium and low methoxylated pectin (LMP), which is an anionic polysaccharide, and calcium, LMP, and sodium alginate. Beads were dried separately in an air convection type oven at 40 degrees C for 6 hours and in a freeze dryer to evaluate the changes in bead characteristics due to process variability. Riboflavin (B-2), tetracycline (TCN), and Methotrexate (MTX) were used as model drugs for encapsulation. Ionic and nonionic excipients were added to study their effects on the release profiles of the beads. The presence of noncross linking agents in low amounts (less than 2%) did not significantly interfere with release kinetics. For an amphoteric drug like TCN, which has pH dependent solubility, three different pHs (1.5, 5.0, and 8.0) of cross-linking media were used to evaluate the effects of pH on the drug entrapment capacity of the beads. As anticipated, highest entrapment was possible when cross-linking media pH coincided with least drug solubility. Evaluation of the drying process demonstrated that the freeze-dried beads remained buoyant over 12 hours in United States Pharmacopeia (USP) hydrochloride buffer at pH 1.5, whereas the air-dried beads remained submerged throughout the release study. Confocal laser microscopy revealed the presence of air-filled hollow spaces inside the freeze dried beads, which was responsible for the flotation property of the beads. However, the release kinetics from freeze dried beads was independent of hydrodynamic conditions. Calcium-pectinate-alginate beads released their contents at much faster rates than did calcium-pectinate beads (100% in 10 hours vs. 50% in 10 hours). It appears that the nature of cross-linking, drying method, drug solubility, and production approach are all important and provide the opportunity and potential for development of a

  13. Effect of ethanol on droplet size, efficiency of delivery, and clearance characteristics of technetium-99m DTPA aerosol

    SciTech Connect

    Sirr, S.A.; Juenemann, P.J.; Tom, H.; Boudreau, R.J.; Chandler, R.P.; Loken, M.K.

    1985-06-01

    With recent technical advances in aerosol technology, the study of regional ventilation using (/sup 99m/Tc)DTPA aerosol has become increasingly popular. Using a cascade impactor, the authors have assessed droplet size distribution from a newly designed nebulizer. Delivery efficiency of (/sup 99m/Tc)DTPA aerosol to normal subjects was improved 70% with a 10% concentration of ethanol in the nebulizer. Using filter paper fixed to the delivery end of the aerosol device, and varying ethanol concentrations from 0-10%, an 87% increase of deposited radioactivity is measured. The addition of ethanol did not alter clearance characteristics of (/sup 99m/Tc)DTPA from the lung nor did it affect droplet size distribution.

  14. Viral and nonviral delivery systems for gene delivery.

    PubMed

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

    2012-01-01

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

  15. A System to Create Stable Nanoparticle Aerosols from Nanopowders.

    PubMed

    Ding, Yaobo; Riediker, Michael

    2016-01-01

    Nanoparticle aerosols released from nanopowders in workplaces are associated with human exposure and health risks. We developed a novel system, requiring minimal amounts of test materials (min. 200 mg), for studying powder aerosolization behavior and aerosol properties. The aerosolization procedure follows the concept of the fluidized-bed process, but occurs in the modified volume of a V-shaped aerosol generator. The airborne particle number concentration is adjustable by controlling the air flow rate. The system supplied stable aerosol generation rates and particle size distributions over long periods (0.5-2 hr and possibly longer), which are important, for example, to study aerosol behavior, but also for toxicological studies. Strict adherence to the operating procedures during the aerosolization experiments ensures the generation of reproducible test results. The critical steps in the standard protocol are the preparation of the material and setup, and the aerosolization operations themselves. The system can be used for experiments requiring stable aerosol concentrations and may also be an alternative method for testing dustiness. The controlled aerosolization made possible with this setup occurs using energy inputs (may be characterized by aerosolization air velocity) that are within the ranges commonly found in occupational environments where nanomaterial powders are handled. This setup and its operating protocol are thus helpful for human exposure and risk assessment. PMID:27501179

  16. Starch Applications for Delivery Systems

    NASA Astrophysics Data System (ADS)

    Li, Jason

    2013-03-01

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

  17. Pulmonary Drug Delivery System for inhalation therapy in mechanically ventilated patients.

    PubMed

    Dhand, Rajiv; Sohal, Harjyot

    2008-01-01

    The Pulmonary Drug Delivery System (PDDS) Clinical represents a newer generation of electronic nebulizers that employ a vibrating mesh or aperture plate to generate an aerosol. The PDDS Clinical is designed for aerosol therapy in patients receiving mechanical ventilation. The components of the device include a control module that is connected to the nebulizer/reservoir unit by a cable. The nebulizer contains Aerogen's OnQ aerosol generator. A pressure sensor monitors the pressure in the inspiratory limb of the ventilator circuit and provides feedback to the control module. Based on the feedback from the pressure sensor, aerosol generation occurs only during a specific part of the respiratory cycle. In bench models, the PDDS Clinical has high efficiency for aerosol delivery both on and off the ventilator, with a lower respiratory tract delivery of 50-70% of the nominal dose. Currently, the PDDS Clinical is being evaluated for the treatment of ventilator-associated pneumonia with aerosolized amikacin, an aminoglycoside antibiotic. Preliminary studies in patients with ventilator-associated pneumonia found that the administration of amikacin via PDDS reduced the need for concomitant intravenous antibiotics; however, more definitive clinical studies are needed. The PDDS Clinical delivers a high percentage of the nominal dose to the lower respiratory tract, and is well suited for inhalation therapy in mechanically ventilated patients. PMID:18095891

  18. Fibrin Glue as a Drug Delivery System

    PubMed Central

    Spicer, Patrick P.; Mikos, Antonios G.

    2010-01-01

    Fibrin glue has been used surgically for decades for hemostasis as well as a sealant. It has also been researched as both a gel for cell delivery and a vehicle for drug delivery. The drug delivery applications for fibrin glue span tissue engineering to chemotherapy and involve several mechanisms for drug matrix interactions and control of release kinetics. Additionally, drugs or factors can be loaded in the gel via impregnation and tethering to the gel through covalent linkages or affinity based systems. This review highlights recent research of fibrin glue as a drug delivery vehicle. PMID:20637815

  19. Ionization detection system for aerosols

    DOEpatents

    Jacobs, Martin E.

    1977-01-01

    This invention relates to an improved smoke-detection system of the ionization-chamber type. In the preferred embodiment, the system utilizes a conventional detector head comprising a measuring ionization chamber, a reference ionization chamber, and a normally non-conductive gas triode for discharging when a threshold concentration of airborne particulates is present in the measuring chamber. The improved system utilizes a measuring ionization chamber which is modified to minimize false alarms and reductions in sensitivity resulting from changes in ambient temperature. In the preferred form of the modification, an annular radiation shield is mounted about the usual radiation source provided to effect ionization in the measuring chamber. The shield is supported by a bimetallic strip which flexes in response to changes in ambient temperature, moving the shield relative to the source so as to vary the radiative area of the source in a manner offsetting temperature-induced variations in the sensitivity of the chamber.

  20. Distribution of polyphenols and a surfactant component in skin during Aerosol OT microemulsion-enhanced intradermal delivery.

    PubMed

    Yutani, Reiko; Morita, Shin-ya; Teraoka, Reiko; Kitagawa, Shuji

    2012-01-01

    As for most other polyphenols, intradermal delivery of curcumin and resveratrol is limited; however, it was significantly improved by a microemulsion using Aerosol OT (Aerosol OT microemulsion) and Tween 80 (Tween 80 microemulsion) as surfactants. Aerosol OT microemulsion was more effective and the incorporation ratio of these polyphenols into skin by Aerosol OT microemulsion was five-fold or ten-fold that by Tween 80 microemulsion. To clarify the mechanism of the enhancement we examined the distribution of these polyphenols and the surfactant component, Aerosol OT, using excised guinea pig skin and Yucatan micropig (YMP) skin. During permeation, polyphenols distributed deep in the skin. In particular, a small molecule, resveratrol, was mainly present in the dermis in YMP skin. Aerosol OT also distributed deep in the skin. These findings suggest the possible involvement of the interaction of surfactant molecules with skin components in the enhanced delivery process of polyphenols. The distribution ratio between the dermis and epidermis of the polyphenols, including quercetin, in the presence of Aerosol OT microemulsion decreased with the increase of molecular weight in YMP skin, suggesting the possibility that distribution to the dermis is regulated by the molecular size. PMID:22863702

  1. Fiber laser coupled optical spark delivery system

    DOEpatents

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

    2008-03-04

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

  2. Delivery system for laser medical instrument

    NASA Astrophysics Data System (ADS)

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

    2003-10-01

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

  3. A nonhuman primate toxicology and immunogenicity study evaluating aerosol delivery of AERAS-402/Ad35 vaccine

    PubMed Central

    Hokey, David A; Wachholder, Robert; Darrah, Patricia A; Bolton, Diane L; Barouch, Dan H; Hill, Krystal; Dheenadhayalan, Veerabadran; Schwander, Stephan; Godin, C Steven; Douoguih, Macaya; Pau, Maria Grazia; Seder, Robert A; Roederer, Mario; Sadoff, Jerald C; Sizemore, Donata

    2014-01-01

    Bacille Calmette-Guérin (BCG), the only licensed vaccine for the prevention of tuberculosis (TB), provides only limited protection against certain forms of Mycobacterium tuberculosis (Mtb) infection. While infection with Mtb can be treated with antibiotics, the therapy is expensive, toxic, and requires several months for treatment. In addition, the emergence of drug resistant strains limits the impact of antibiotics and underlines the importance of developing a more effective vaccine to control this disease. Given that pulmonary TB is the most common form of the disease, a vaccine capable of inducing lung-resident immunity may be advantageous for combating this infection. New advances in pulmonary delivery make this route of vaccination feasible and affordable. Here, we evaluate the safety and immunogenicity of an aerosolized Ad35-based vaccine, AERAS-402, delivered to the lungs in nonhuman primates as part of a GLP acute and chronic toxicology and safety study. In this study, animals received three high doses (1 x 1011 vp) of AERAS-402 by inhalation via a nebulizer at 1-week intervals. Aerosol delivery of AERAS-402 resulted in an increase in relative lung weights as well as microscopic findings in the lungs, mediastinal lymph nodes, bronchus-associated lymphatic tissue, and the naso-oropharynx that were consistent with the induction of an immune response during the acute phase. These findings resolved by the chronic phase and were considered to be non-adverse. Furthermore, we observed transient vaccine-specific immune responses in the peripheral blood as well as sustained high-level polyfunctional CD4+ and CD8+ T cell responses in the bronchoalveolar lavage fluid of vaccinated nonhuman primates. The data suggest that pulmonary delivery of Ad35-based vaccines can be safe and can induce potent lung-resident immunity. PMID:25424923

  4. Aerosol Delivery of Interleukin-2 in Combination with Adoptive Transfer of Natural Killer Cells for the Treatment of Lung Metastasis: Methodology and Effect.

    PubMed

    Kiany, Simin; Gordon, Nancy

    2016-01-01

    Natural killer (NK) cells are a subtype of lymphocytes with a major role as a host defense mechanism against tumor cells. Allogeneic NK cell therapy is being used as an alternative promising therapy for many different cancers. Interleukin-2 (IL-2) is a critical cytokine for NK cell proliferation, survival, and effector functions. Cytokine support is essential to activate, expand, and increase the life span of NK cells. Aerosol delivery of IL-2 in combination with adoptive transfer of NK cells offers a reasonable approach for the treatment of lung metastases as it avoids the deleterious side effects of systemic IL-2. Using a human OS mouse model, we demonstrated the efficacy of this approach. Combination therapy of aerosol IL-2 with NK cells resulted in a better therapeutic effect against OS lung metastases as compared with each therapy alone. Aerosol IL-2 selectively increased infiltration, retention, and proliferation of infused NK cells in the lung, and there was no local inflammation or toxicity in the lungs or any other organ. Our results demonstrate that delivery of IL-2 via the aerosol route offers a feasible and innovative approach to enhance the immunotherapeutic effect of NK cells against pulmonary metastases. In the following chapter, we describe the methodology and effect of this innovative therapeutic approach. PMID:27177675

  5. Hydrogen storage and delivery system development

    SciTech Connect

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

    1995-09-01

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

  6. Alternative delivery systems in rural areas.

    PubMed Central

    Christianson, J B

    1989-01-01

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

  7. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

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

  8. Delivery systems for intradermal vaccination.

    PubMed

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

    2012-01-01

    Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development. PMID:21472533

  9. WEDDS: The WITS Encrypted Data Delivery System

    NASA Technical Reports Server (NTRS)

    Norris, J.; Backes, P.

    1999-01-01

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

  10. Novel drug delivery systems for glaucoma

    PubMed Central

    Lavik, E; Kuehn, M H; Kwon, Y H

    2011-01-01

    Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

  11. Cyclodextrins in delivery systems: Applications

    PubMed Central

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

    2010-01-01

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

  12. Transmucosal delivery systems for calcitonin: a review.

    PubMed

    Torres-Lugo, M; Peppas, N A

    2000-06-01

    The commercial availability of peptides and proteins and their advantages as therapeutic agents have been the basis for tremendous efforts in designing delivery systems for such agents. The protection of these agents from biological fluids and physiological interactions is crucial for the treatment efficacy. One such agent is salmon calcitonin, a 32 amino-acid polypeptide hormone used in the treatment of bone diseases such as Paget's disease, hypercalcemia and osteoporosis. Researchers have studied different routes to deliver salmon calcitonin more effectively, including nasal, oral, vaginal and rectal delivery. These systems are designed to protect the polypeptide from the biological barriers that each delivery route imposes. Oil-based and polymer-based delivery systems are discussed. PMID:10811300

  13. Planetary Regolith Delivery Systems for ISRU

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  14. Development of a Scheimpflug Lidar System for Atmospheric Aerosol Monitoring

    NASA Astrophysics Data System (ADS)

    Mei, Liang; Brydegaard, Mikkel

    2016-06-01

    This work presents a Scheimpflug lidar system which was employed for atmospheric aerosol monitoring in southern Sweden. Atmospheric aerosol fluctuation was observed around rush-hour. The extinction coefficient over 6 km was retrieved, i.e., 0.15 km-1, by employing the slop-method during the time when the atmosphere was relatively homogenous. The measurements successfully demonstrate the potential of using a Scheimpflug lidar technique for atmospheric aerosol monitoring applications.

  15. Aerosol mass spectrometry systems and methods

    SciTech Connect

    Fergenson, David P.; Gard, Eric E.

    2013-08-20

    A system according to one embodiment includes a particle accelerator that directs a succession of polydisperse aerosol particles along a predetermined particle path; multiple tracking lasers for generating beams of light across the particle path; an optical detector positioned adjacent the particle path for detecting impingement of the beams of light on individual particles; a desorption laser for generating a beam of desorbing light across the particle path about coaxial with a beam of light produced by one of the tracking lasers; and a controller, responsive to detection of a signal produced by the optical detector, that controls the desorption laser to generate the beam of desorbing light. Additional systems and methods are also disclosed.

  16. Dry powder aerosols of polyethylenimine (PEI)-based gene vectors mediate efficient gene delivery to the lung.

    PubMed

    Pfeifer, Corinna; Hasenpusch, Guenther; Uezguen, Senta; Aneja, Manish Kumar; Reinhardt, Dietrich; Kirch, Julian; Schneider, Marc; Claus, Sarah; Friess, Wolfgang; Rudolph, Carsten

    2011-08-25

    Aerosol gene delivery holds great therapeutical potential for many inherited and acquired pulmonary diseases. The physical instability of aqueous suspensions of non-viral vector complexes is a major limitation for their successful application. In this study, we investigated dry powder aerosols as novel gene vector formulations for gene transfer in vitro and murine lungs in vivo. Lyophilization was used to produce dry powder cakes followed by powderization to produce dry powder aerosols. Different sugars, namely lactose, sucrose and trehalose, were tested as lyoprotectants for gene delivery complexes consisting of branched polyethylenimine 25 kDa and plasmid DNA. Biophysical particle characterization demonstrated that lyophilization and powderization in the presence of lyoprotectants were well tolerated. In vitro transfection efficiency remained unaffected by the choice of lyoprotectant and subsequent lyophilization and/or powderization. In vivo screening of powderized samples, by applying the powder with an insufflator, resulted in highest gene expression with lactose as lyoprotectant. Delivering a plasmid coding for murine erythropoietin together with lactose as lyoprotectant resulted in increased blood hematocrit values post application thereby demonstrating the potential of dry powder aerosol as a promising method for pulmonary gene delivery. PMID:21600251

  17. Renewable energy delivery systems and methods

    DOEpatents

    Walker, Howard Andrew

    2013-12-10

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

  18. Deep Space Systems Technology Program Future Deliveries

    NASA Technical Reports Server (NTRS)

    Salvo, Christopher G.; Keuneke, Matthew S.

    2000-01-01

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

  19. Brain drug delivery systems for neurodegenerative disorders.

    PubMed

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

    2012-09-01

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

  20. Neutral and charged binary sulfate aerosol nucleation in the aerosol-climate modeling system ECHAM5-HAM

    NASA Astrophysics Data System (ADS)

    Kazil, J.; Kokkola, H.

    2007-12-01

    Aerosol particles play an important role in the Earth's atmosphere and in the climate system: Aerosols scatter and absorb solar radiation, facilitate heterogeneous and multiphase chemistry, and change cloud characteristics in many ways. Aerosol particles can be directly emitted from surface sources (primary aerosol) or form from the gas phase (secondary aerosol). Secondary aerosol formation can significantly increase concentrations of cloud condensation nuclei. Two important pathways of aerosol formation from the gas phase are neutral and charged binary nucleation of sulfuric acid and water. We have introduced laboratory data based representations of these pathways into the aerosol-climate modeling system ECHAM5-HAM, and investigate their relative importance and spatial distribution in the troposphere, and discuss ramifications for processes in the Earth's atmosphere.

  1. [Progression of drug delivery system for glaucoma].

    PubMed

    Xu, Yan; Lyu, Liu

    2014-12-01

    Reduction of intraocular pressure (IOP) by drugs is a major treatment for glaucoma. Clinically, diverse antiglaucoma drugs take effect to decrease the IOP through different mechanisms.However, due to limitations of traditional form of eye drops, the bioavailability of the drug and the patient compliance is lowered, the clinical efficacy is not good and also some toxic and side-effects come out.Otherwise, traditional medication is not suitable for neuroprotective drugs to work on both retina and optic nerve. Drug delivery system has the potential to improve the bioavailability of the drug, prolong the time of drug action, decrease the dosage and frequency of drugs, reduce the side-effects, and improve the patient compliance and efficacy.It is one of the most important studies in glaucoma medication development because it is valuable for patients' neuroprotection.Nowadays, several novel delivery systems have been designed. This review will focus on the progressions of some of the sustained-release antiglaucoma eye drops, polymeric gels, colloidal systems, membrane-controlled drug delivery system, ocular implants, and transscleral drug delivery systems. PMID:25619186

  2. Use of a hand-held, metered-dose aerosol delivery device to administer pirbuterol acetate to horses with 'heaves'.

    PubMed

    Derksen, F J; Olszewski, M; Robinson, N E; Berney, C; Lloyd, J W; Hakala, J; Matson, C; Ruth, D

    1996-07-01

    Aerosol administration of bronchodilators to horses is recommended for treatment of certain airway diseases such as 'heaves'. We have developed a novel, hand-held, metered-dose inhaler and we sought to determine the bronchodilator efficacy of the beta 2 adrenoceptor agonist pirbuterol delivered by this device to horses affected with 'heaves'. To induce airway obstruction, 6 heaves-susceptible horses were stabled, bedded on straw and fed hay. When the maximum change in pleural pressure during tidal breathing (delta Pplmax) was greater than 20 cmH2O on 2 consecutive days, pulmonary function was measured before and 5, 10 and 30 min, as well as 1, 2, 3, 4, 5, 6 and 7 h after administration of aerosol pirbuterol. Pirbuterol was administered using a metered canister and the hand-held delivery device that was inserted into the left nostril. Either vehicle or pirbuterol acetate (400, 600, 800, 1200 or 1600 micrograms) was administered to each horse. Relief of airway obstruction indicated by changes in pulmonary function was observed within 5 min after administration of both vehicle and pirbuterol. Significant decreases in delta Pplmax and pulmonary resistance (RL) and an increase in dynamic compliance (Cdyn) persisted for the 7 h duration of the experiment. Comparison of the effect of vehicle and pirbuterol at each time period showed that pirbuterol decreased RL and delta Pplmax significantly for up to 1 h. The optimal dose was determined to be 600 micrograms. Immediate response to treatment, magnitude of drug effect and lack of side effects indicated that aerosol pirbuterol is an effective and safe bronchodilator in horses with 'heaves'. The hand-held, metered-dose aerosol delivery device was very convenient and extremely effective and is, therefore, recommended for delivery of therapeutic aerosols to horses. PMID:8818596

  3. Waste Feed Delivery Transfer System Analysis

    SciTech Connect

    JULYK, L.J.

    2000-05-05

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

  4. Drug Delivery Systems: Entering the Mainstream

    NASA Astrophysics Data System (ADS)

    Allen, Theresa M.; Cullis, Pieter R.

    2004-03-01

    Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.

  5. Preparation and physicochemical characterization of dioctyl sodium sulfosuccinate (aerosol OT) microemulsion for oral drug delivery.

    PubMed

    El-Laithy, Hanan M

    2003-01-01

    The performance of dioctyl sodium sulfosuccinate (aerosol OT) in the development of a pharmaceutically acceptable, stable, self-emulsifying water continuous microemulsion with high dilution efficiency was assessed. A pseudoternary microemulsion system was constructed using aerosol OT/medium-chain triglycerides with oleic acid/glycerol monooleate and water. The model microemulsion was characterized with regard to its electroconductive behavior, eosin sodium absorption, interfacial tension, and droplet size measurements after dilution with water. The percolation transition law, which makes it possible to determine the percolation threshold and to identify bicontinuous structures, was applied to the system. The interfacial tension changes associated with the microemulsion formation revealed ultralow values up to 30% oil at a surfactant/cosurfactant ratio of 3:1. Moreover, the investigated particle size and polydispersity using photon correlation spectroscopy after dilution with excess of the continuous phase proved the efficiency of the microemulsion system as a drug carrier that ensures an infinitely dilutable, homogeneous, and thermodynamically stable system. PMID:12916920

  6. The Cloud-Aerosol Transport System (CATS): Demonstrating New Techniques for Cloud and Aerosol Measurements

    NASA Astrophysics Data System (ADS)

    Yorks, J. E.; McGill, M. J.; Palm, S. P.; Hlavka, D. L.; Nowottnick, E. P.; Selmer, P. A.

    2015-12-01

    The Cloud-Aerosol Transport System (CATS) is an elastic backscatter lidar that provides vertical profiles of cloud and aerosol properties. The CATS payload has been operating since early February 2015 from the International Space Station (ISS). CATS was designed to operate for six months, and up to three years, providing a combination of operational science, in-space technology demonstration, and technology risk reduction for future Earth Science missions. One of the primary project goals of CATS is to demonstrate technology in support of future space-based lidar mission development. The CATS instrument has been demonstrating the high repetition rate laser and photon counting detection approach to lidar observations, in contrast to the low repetition rate, high energy technique employed by CALIPSO. Due to this technique, cloud and aerosol profile data exhibit high spatial and temporal resolution, which was never before possible from a space-based platform. Another important science goal of the CATS-FO project is accurate determination of aerosol type on a global scale. CATS provided the first space-based depolarization measurements at multiple wavelengths (532 and 1064 nm), and first measurements at 1064 nm from space. The ratio of the depolarization measurements at these two wavelengths enables significant improvement in aerosol typing. The CATS retrievals at 1064 nm also provide improvements to detecting aerosols above clouds. The CATS layer identification algorithm is a threshold-based layer detection method that uses the 1064 nm attenuated scattering ratio and also includes a routine to identify clouds embedded within aerosol layers. This technique allows CATS to detect the full extent of the aerosol layers above the cloud, and differentiate these two layers so that the optical properties can be more accurately determined.

  7. Human Services Course Delivery Systems.

    ERIC Educational Resources Information Center

    Soong, Robert K.; And Others

    This paper deals with various teaching methods and techniques currently is use in junior colleges in the Chicago area including traditional as well as innovative methods. The basic assumption is that teaching and learning are both essential aspects of the same system. The human services field is defined as encompassing the basic area of social…

  8. Systemic delivery of artemether by dissolving microneedles.

    PubMed

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

    2016-07-11

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

  9. Lipid-Based Drug Delivery Systems

    PubMed Central

    Shrestha, Hina; Bala, Rajni; Arora, Sandeep

    2014-01-01

    The principle objective of formulation of lipid-based drugs is to enhance their bioavailability. The use of lipids in drug delivery is no more a new trend now but is still the promising concept. Lipid-based drug delivery systems (LBDDS) are one of the emerging technologies designed to address challenges like the solubility and bioavailability of poorly water-soluble drugs. Lipid-based formulations can be tailored to meet a wide range of product requirements dictated by disease indication, route of administration, cost consideration, product stability, toxicity, and efficacy. These formulations are also a commercially viable strategy to formulate pharmaceuticals, for topical, oral, pulmonary, or parenteral delivery. In addition, lipid-based formulations have been shown to reduce the toxicity of various drugs by changing the biodistribution of the drug away from sensitive organs. However, the number of applications for lipid-based formulations has expanded as the nature and type of active drugs under investigation have become more varied. This paper mainly focuses on novel lipid-based formulations, namely, emulsions, vesicular systems, and lipid particulate systems and their subcategories as well as on their prominent applications in pharmaceutical drug delivery. PMID:26556202

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

    PubMed

    2005-03-01

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

  11. Insulin-like growth factor-I aerosol formulations for pulmonary delivery.

    PubMed

    Germershaus, Oliver; Schultz, Isabel; Lühmann, Tessa; Beck-Broichsitter, Moritz; Högger, Petra; Meinel, Lorenz

    2013-09-01

    Injectable insulin-like growth factor-1 (IGF-I) is therapeutically deployed for severe IGF-I deficiency and clinically explored for various other indications such as muscle wasting disease. In the present study, liquid IGF-I formulations for pulmonal application were screened with regard to buffer type (acetate, citrate, histidine, and succinate), sodium chloride concentration (50-150 mM), and pH value (4.5-6.5). Methionine 59 oxidation (Met(o)) was observed in acetate buffer along with reducible dimer and trimer formation at low pH. Oxidation correlated with formation of covalent, reducible aggregates, and complete loss of potency was observed for severely aggregated samples. Bioactivity was partly retained in cases where complete oxidation but limited aggregation was found. In contrast, IGF-I integrity was preserved in histidine buffer during accelerated stability. After delivery from air-jet or vibrating-mesh nebulizers, limited Met(o) formation and no aggregation was observed. Nebulization performance regarding aerosol output rate, mass median aerodynamic diameter, and fine particle fraction for liquid IGF-I formulation was comparable to 0.9% sodium chloride reference, confirming the suitability for pulmonal application. In conclusion, different IGF-I liquid formulations were studied and compositions were identified maintaining bioactivity and chemical stability throughout storage at accelerated conditions for up to 4 months as well as compatibility with air-jet and vibrating-mesh nebulizers. PMID:23958318

  12. In vitro study and semiempirical model for aerosol delivery control during mechanical ventilation.

    PubMed

    Vecellio, Laurent; Guérin, Claude; Grimbert, Daniel; De Monte, Michele; Diot, Patrice

    2005-06-01

    The object of this study was to evaluate in vitro the influence of various ventilatory parameters on the delivery of synchronized nebulization of terbutaline during mechanical ventilation and to determine a semiempirical model to control the quantity of aerosol delivered into the patient's lung. An ATOMISOR NL9 M jet nebulizer (La Diffusion Technique Francaise, France) was filled with terbutaline (Bricanyl, Astra-Zeneca, Sweden) and connected to the inspiratory line of a Horus ventilator (Taema, France). Nebulization was synchronized with the inspiratory phase. We assessed at the end of the endotracheal tube the quantity of terbutaline (terbutaline mass output) and the volume median diameter (VMD) by diffraction-laser method. There was a negative correlation between terbutaline mass output and inspiratory air flow ( r =-0.95, p <0.0001) and between VMD and inspiratory air flow ( r =-0.96, p <0.0001). Moreover, positive end-expiratory pressure levels between 0 cm and 8 cm of water did not significantly change the terbutaline output mass ( p =0.22). Total nebulization time and terbutaline mass output calculated by the mathematical model showed good agreement with experimental data. In conclusion, our semiempirical model allows calculation of the duration of the nebulization required to deliver a given mass of terbutaline into patient lungs. PMID:15803302

  13. Meteorological and Aerosol Sensing with small Unmanned Aerial Systems

    NASA Astrophysics Data System (ADS)

    Born, J.; Möhler, O.; Haunold, W.; Schrod, J.; Brooks, I.; Norris, S.; Brooks, B.; Hill, M.; Leisner, T.

    2012-04-01

    Unmanned Aerial Systems (UAS) facilitate the monitoring of several meteorological and aerosol parameters with high resolution in space and time. They are small, easy to operate, cost efficient and allow for flexible application during field campaigns. We present two experimental payloads for measurement of relative humidity, temperature, aerosol size distribution and the collection of aerosol samples on board the small UAS SIRIUS II. The payload modules are light weight (<1kg) and can be easily switched between two flights. All sensors can be controlled from the ground and the measured data is recorded by the autopilot together with the position data. The first module contains a sensor package for measurement of relative humidity and temperature and the Compact Lightweight Aerosol Spectrometer Prope (CLASP) for acquisition of aerosol size distributions. CLASP measures aerosol particles with diameters from 0.12μm to 9.25μm in up to 32 channels at a frequency of 10 Hz. The second module also contains a humidity and temperature sensor package and the aerosol sample collection device. The aerosol sampler collects air samples at 2 l/min onto a sample holder. After the flight the ice nuclei on the sample holder are activated in the lab and counted. In August 2012 the complete setup will be used during a measurement campaign at mount "Kleiner Feldberg" close to Frankfurt. Until then we will perform test flights and additional laboratory tests.

  14. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

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

  15. Challenges in media delivery systems and servers

    NASA Astrophysics Data System (ADS)

    Swaminathan, Viswanathan

    2005-03-01

    Although multimedia compression formats and protocols to stream such content have been around for a long time, there has been limited success in the adoption of open standards for streaming over IP (Internet Protocol) networks. The elements of such an end-to-end system will be introduced outlining the responsibilities of each element. The technical and financial challenges in building a viable multimedia streaming end-to-end system will be analyzed in detail in this paper outlining some solutions and areas for further research. Also, recent migration to IP in the backend video delivery network infrastructures have made it possible to use IP based media streaming solutions in non-IP last mile access networks like cable and wireless networks in addition to the DSL networks. The advantages of using IP streaming solutions in such networks will be outlined. However, there is a different set of challenges posed by such applications. The real time constraints are acute in each element of the media delivery end-to-end system. Meeting these real time constraints in general purpose non real time server systems is quite demanding. Quality of service, resource management, session management, fail-over, reliability, and cost are some important but challenging requirements in such systems. These will also be analyzed with suggested solutions. Content protection and rights management requirements are also very challenging for open standards based multimedia delivery systems. Interoperability unfortunately interferes with security in most of the current day systems. Some approaches to solve the interoperability problems will also be presented. The requirements, challenges, and possible solutions for delivering broadcast, on demand, and interactive video delivery applications for IP based media streaming systems will be analyzed in detail.

  16. Biomaterials for Nanoparticle Vaccine Delivery Systems

    PubMed Central

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

    2014-01-01

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

  17. Hydrogen storage and delivery system development: Fabrication

    SciTech Connect

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

    1996-10-01

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

  18. Smart Magnetically Responsive Hydrogel Nanoparticles Prepared by a Novel Aerosol-Assisted Method for Biomedical and Drug Delivery Applications

    PubMed Central

    El-Sherbiny, Ibrahim M.; Smyth, Hugh D. C.

    2011-01-01

    We have developed a novel spray gelation-based method to synthesize a new series of magnetically responsive hydrogel nanoparticles for biomedical and drug delivery applications. The method is based on the production of hydrogel nanoparticles from sprayed polymeric microdroplets obtained by an air-jet nebulization process that is immediately followed by gelation in a crosslinking fluid. Oligoguluronate (G-blocks) was prepared through the partial acid hydrolysis of sodium alginate. PEG-grafted chitosan was also synthesized and characterized (FTIR, EA, and DSC). Then, magnetically responsive hydrogel nanoparticles based on alginate and alginate/G-blocks were synthesized via aerosolization followed by either ionotropic gelation or both ionotropic and polyelectrolyte complexation using CaCl2 or PEG-g-chitosan/CaCl2 as crosslinking agents, respectively. Particle size and dynamic swelling were determined using dynamic light scattering (DLS) and microscopy. Surface morphology of the nanoparticles was examined using SEM. The distribution of magnetic cores within the hydrogels nanoparticles was also examined using TEM. In addition, the iron and calcium contents of the particles were estimated using EDS. Spherical magnetic hydrogel nanoparticles with average particle size of 811 ± 162 to 941 ± 2 nm were obtained. This study showed that the developed method is promising for the manufacture of hydrogel nanoparticles, and it represents a relatively simple and potential low-cost system. PMID:21808638

  19. Aerosol generation by blower motors as a bias in assessing aerosol penetration into cabin filtration systems.

    PubMed

    Heitbrink, William A; Collingwood, Scott

    2005-01-01

    In cabin filtration systems, blower motors pressurize a vehicle cabin with clean filtered air and recirculate air through an air-conditioning evaporator coil and a heater core. The exposure reduction offered by these cabins is evaluated by optical particle counters that measure size-dependent aerosol concentration inside and outside the cabin. The ratio of the inside-to-outside concentration is termed penetration. Blower motors use stationary carbon brushes to transmit an electrical current through a rotating armature that abrades the carbon brushes. This creates airborne dust that may affect experimental evaluations of aerosol penetration. To evaluate the magnitude of these dust emissions, blower motors were placed in a test chamber and operated at 12 and 13.5 volts DC. A vacuum cleaner drew 76 m3/hour (45 cfm) of air through HEPA filters, the test chamber, and through a 5 cm diameter pipe. An optical particle counter drew air through an isokinetic sampling probe and measured the size-dependent particle concentrations from 0.3 to 15 microm. The concentration of blower motor aerosol was between 2 x 10(5) and 1.8 x 10(6) particles/m3. Aerosol penetration into three stationary vehicles, two pesticide application vehicles and one tractor were measured at two conditions: low concentration (outside in the winter) and high concentration (inside repair shops and burning incense sticks used as a supplemental aerosol source). For particles smaller than 1 microm, the in-cabin concentrations can be explained by the blower motor emissions. For particles larger than 1 microm, other aerosol sources, such as resuspended dirt, are present. Aerosol generated by the operation of the blower motor and by other sources can bias the exposure reduction measured by optical particle counters. PMID:15764523

  20. Hydrogen storage and delivery system development: Analysis

    SciTech Connect

    Handrock, J.L.

    1996-10-01

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

  1. Recent technologies in pulsatile drug delivery systems

    PubMed Central

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

    2011-01-01

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

  2. Resistive-wall wake effect in the beam delivery system

    SciTech Connect

    J.R. Delayen; Juhao Wu; T.O. Raubenheimer; Jiunn-Ming Wang

    2004-08-16

    General formulae for resistive-wall induced beam dilution are presented and then applied to the final beam delivery system of linear colliders. Criteria for the design of final beam delivery systems are discussed.

  3. Drug delivery system and breast cancer cells

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  4. Drug delivery system and breast cancer cells

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications.

  5. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    PubMed Central

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

    2014-01-01

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

  6. Nanotechnology and pharmaceutical inhalation aerosols.

    PubMed

    Patel, A R; Vavia, P R

    2007-02-01

    Pharmaceutical inhalation aerosols have been playing a crucial role in the health and well being of millions of people throughout the world for many years. The technology's continual advancement, the ease of use and the more desirable pulmonary-rather-than-needle delivery for systemic drugs has increased the attraction for the pharmaceutical aerosol in recent years. But administration of drugs by the pulmonary route is technically challenging because oral deposition can be high, and variations in inhalation technique can affect the quantity of drug delivered to the lungs. Recent advances in nanotechnology, particularly drug delivery field have encouraged formulation scientists to expand their reach in solving tricky problems related to drug delivery. Moreover, application of nanotechnology to aerosol science has opened up a new category of pharmaceutical aerosols (collectively known as nanoenabled-aerosols) with added advantages and effectiveness. In this review, some of the latest approaches of nano-enabled aerosol drug delivery system (including nano-suspension, trojan particles, bioadhesive nanoparticles and smart particle aerosols) that can be employed successfully to overcome problems of conventional aerosol systems have been introduced. PMID:17375556

  7. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

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

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems. PMID:26898739

  8. Towards more effective advanced drug delivery systems.

    PubMed

    Crommelin, Daan J A; Florence, Alexander T

    2013-09-15

    This position paper discusses progress made and to be made with so-called advanced drug delivery systems, particularly but not exclusively those in the nanometre domain. The paper has resulted from discussions with a number of international experts in the field who shared their views on aspects of the subject, from the nomenclature used for such systems, the sometimes overwrought claims made in the era of nanotechnology, the complex nature of targeting delivery systems to specific destinations in vivo, the need for setting standards for the choice and characterisation of cell lines used in in vitro studies, to attention to the manufacturability, stability and analytical profiling of systems and more relevant studies on toxicology. The historical background to the development of many systems is emphasised. So too is the stochastic nature of many of the steps to successful access to and action in targets. A lacuna in the field is the lack of availability of data on a variety of carrier systems using the same models in vitro and in vivo using standard controls. The paper asserts that greater emphasis must also be paid to the effective levels of active attained in target organs, for without such crucial data it will be difficult for many experimental systems to enter the clinic. This means the use of diagnostic/imaging technologies to monitor targeted drug delivery and stratify patient groups, identifying patients with optimum chances for successful therapy. Last, but not least, the critical importance of the development of science bases for regulatory policies, scientific platforms overseeing the field and new paradigms of financing are discussed. PMID:23415662

  9. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

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

  10. Hand calculations for transport of radioactive aerosols through sampling systems.

    PubMed

    Hogue, Mark; Thompson, Martha; Farfan, Eduardo; Hadlock, Dennis

    2014-05-01

    Workplace air monitoring programs for sampling radioactive aerosols in nuclear facilities sometimes must rely on sampling systems to move the air to a sample filter in a safe and convenient location. These systems may consist of probes, straight tubing, bends, contractions and other components. Evaluation of these systems for potential loss of radioactive aerosols is important because significant losses can occur. However, it can be very difficult to find fully described equations to model a system manually for a single particle size and even more difficult to evaluate total system efficiency for a polydispersed particle distribution. Some software methods are available, but they may not be directly applicable to the components being evaluated and they may not be completely documented or validated per current software quality assurance requirements. This paper offers a method to model radioactive aerosol transport in sampling systems that is transparent and easily updated with the most applicable models. Calculations are shown with the R Programming Language, but the method is adaptable to other scripting languages. The method has the advantage of transparency and easy verifiability. This paper shows how a set of equations from published aerosol science models may be applied to aspiration and transport efficiency of aerosols in common air sampling system components. An example application using R calculation scripts is demonstrated. The R scripts are provided as electronic attachments. PMID:24667389

  11. The design and performance of the exubera pulmonary insulin delivery system.

    PubMed

    Harper, Nancy J; Gray, Steven; De Groot, Jennifer; Parker, Joann M; Sadrzadeh, Negar; Schuler, Carlos; Schumacher, Jacqueline D; Seshadri, Sangita; Smith, Adrian E; Steeno, Gregory S; Stevenson, Cynthia L; Taniere, Romain; Wang, May; Bennett, David B

    2007-06-01

    The Exubera system (Pfizer, New York, NY/Nektar Therapeutics, San Carlos, CA) is an integration of five major new technologies: protein formulation, powder processing, powder filling, drug packaging, and delivery device. The product provides a simple interface, where the patient interacts only with the delivery device and powder packaging. These components were designed together to assure repeatable dosing when used by a wide range of patients under real-world life-style and handling conditions. The device design is purely mechanical, using patient-generated compressed air as the energy source. Upon actuation, a sonic discharge of air through the novel release unit reproducibly extracts, de-agglomerates, and disperses the inhalation powder into a respirable aerosol. A clear holding chamber allows for patient feedback via dose visualization and separates aerosol cloud generation from the inspiratory effort. The Exubera product was tested under a wide range of typical use conditions and potential misuse scenarios and following long-term usage in clinical trials. These comprehensive characterization programs demonstrated robust aerosol and mechanical performance, confirming the design intent of the inhaler. These studies provide assurance of consistent and reliable dose delivery in a real-world use of the product. PMID:17563300

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

    PubMed

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

    2016-01-01

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

  13. Modeling and Simulations of Olfactory Drug Delivery with Passive and Active Controls of Nasally Inhaled Pharmaceutical Aerosols.

    PubMed

    Si, Xiuhua A; Xi, Jinxiang

    2016-01-01

    There are many advantages of direct nose-to-brain drug delivery in the treatment of neurological disorders. However, its application is limited by the extremely low delivery efficiency (< 1%) to the olfactory mucosa that directly connects the brain. It is crucial to develop novel techniques to deliver neurological medications more effectively to the olfactory region. The objective of this study is to develop a numerical platform to simulate and improve intranasal olfactory drug delivery. A coupled image-CFD method was presented that synthetized the image-based model development, quality meshing, fluid simulation, and magnetic particle tracking. With this method, performances of three intranasal delivery protocols were numerically assessed and compared. Influences of breathing maneuvers, magnet layout, magnetic field strength, drug release position, and particle size on the olfactory dosage were also numerically studied. From the simulations, we found that clinically significant olfactory dosage (up to 45%) were feasible using the combination of magnet layout and selective drug release. A 64 -fold higher delivery of dosage was predicted in the case with magnetophoretic guidance compared to the case without it. However, precise guidance of nasally inhaled aerosols to the olfactory region remains challenging due to the unstable nature of magnetophoresis, as well as the high sensitivity of olfactory dosage to patient-, device-, and particle-related factors. PMID:27285852

  14. Design, assembly, and validation of a nose-only inhalation exposure system for studies of aerosolized viable influenza H5N1 virus in ferrets

    PubMed Central

    2010-01-01

    Background The routes by which humans acquire influenza H5N1 infections have not been fully elucidated. Based on the known biology of influenza viruses, four modes of transmission are most likely in humans: aerosol transmission, ingestion of undercooked contaminated infected poultry, transmission by large droplets and self-inoculation of the nasal mucosa by contaminated hands. In preparation of a study to resolve whether H5N1 viruses are transmissible by aerosol in an animal model that is a surrogate for humans, an inhalation exposure system for studies of aerosolized H5N1 viruses in ferrets was designed, assembled, and validated. Particular attention was paid towards system safety, efficacy of dissemination, the viability of aerosolized virus, and sampling methodology. Results An aerosol generation and delivery system, referred to as a Nose-Only Bioaerosol Exposure System (NBIES), was assembled and function tested. The NBIES passed all safety tests, met expected engineering parameters, required relatively small quantities of material to obtain the desired aerosol concentrations of influenza virus, and delivered doses with high-efficacy. Ferrets withstood a mock exposure trial without signs of stress. Conclusions The NBIES delivers doses of aerosolized influenza viruses with high efficacy, and uses less starting material than other similar designs. Influenza H5N1 and H3N2 viruses remain stable under the conditions used for aerosol generation and sample collection. The NBIES is qualified for studies of aerosolized H5N1 virus. PMID:20573226

  15. Modeling the Delivery Physiology of Distributed Learning Systems.

    ERIC Educational Resources Information Center

    Paquette, Gilbert; Rosca, Ioan

    2003-01-01

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

  16. Advances in Systemic siRNA Delivery

    PubMed Central

    Leng, Qixin; Woodle, Martin C; Lu, Patrick Y; Mixson, A James

    2009-01-01

    Sequence-specific gene silencing with small interfering RNA (siRNA) has transformed basic science research, and the efficacy of siRNA therapeutics toward a variety of diseases is now being evaluated in pre-clinical and clinical trials. Despite its potential value, the highly negatively charged siRNA has the classic delivery problem of requiring transport across cell membranes to the cytosol. Consequently, carrier development for siRNA delivery is one of the most important problems to solve before siRNA can achieve widespread clinical use. An assortment of non-viral carriers including liposomes, peptides, polymers, and aptamers are being evaluated for their ability to shepherd siRNA to the target tissue and cross the plasma membrane barrier into the cell. Several promising carriers with low toxicity and increased specificity for disease targets have emerged for siRNA-based therapeutics. This review will discuss non-viral approaches for siRNA therapeutics, with particular focus on synthetic carriers for in vivo systemic delivery of siRNA. PMID:20161621

  17. Microemulsions based transdermal drug delivery systems.

    PubMed

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

    2014-01-01

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

  18. Liposomes as delivery systems for antineoplastic drugs

    NASA Astrophysics Data System (ADS)

    Medina, Luis Alberto

    2014-11-01

    Liposome drug formulations are defined as pharmaceutical products containing active drug substances encapsulated within the lipid bilayer or in the interior aqueous space of the liposomes. The main importance of this drug delivery system is based on its drastic reduction in systemic dose and concomitant systemic toxicity that in comparison with the free drug, results in an improvement of patient compliance and in a more effective treatment. There are several therapeutic drugs that are potential candidates to be encapsulated into liposomes; particular interest has been focused in therapeutic and antineoplastic drugs, which are characterized for its low therapeutic index and high systemic toxicity. The use of liposomes as drug carriers has been extensively justified and the importance of the development of different formulations or techniques to encapsulate therapeutic drugs has an enormous value in benefit of patients affected by neoplastic diseases.

  19. Fuel delivery system including heat exchanger means

    NASA Technical Reports Server (NTRS)

    Coffinberry, G. A. (Inventor)

    1978-01-01

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

  20. A New Aerosol Flow System for Photochemical and Thermal Studies of Tropospheric Aerosols

    SciTech Connect

    Ezell, Michael J.; Johnson, Stanley N.; Yu, Yong; Perraud, Veronique; Bruns, Emily; Alexander, M. L.; Zelenyuk, Alla; Dabdub, Donald; Finlayson-Pitts, Barbara J.

    2010-05-01

    For studying the formation and photochemical/thermal reactions of aerosols relevant to the troposphere, a unique, high-volume, slow-flow, stainless steel aerosol flow system equipped with 5 UV lamps has been constructed and characterized experimentally. The total flow system length 6 is 8.5 m and includes a 1.2 m section used for mixing, a 6.1 m reaction section and a 1.2 m 7 transition cone at the end. The 45.7 cm diameter results in a smaller surface to volume ratio than is found in many other flow systems and thus reduces the potential contribution from wall reactions. The latter are also reduced by frequent cleaning of the flow tube walls which is made feasible by the ease of disassembly. The flow tube is equipped with ultraviolet lamps for photolysis. This flow system allows continuous sampling under stable conditions, thus increasing the amount of sample available for analysis and permitting a wide variety of analytical techniques to be applied simultaneously. The residence time is of the order of an hour, and sampling ports located along the length of the flow tube allow for time-resolved measurements of aerosol and gas-phase products. The system was characterized using both an inert gas (CO2) and particles (atomized NaNO3). Instruments interfaced directly to this flow system include a NOx analyzer, an ozone analyzer, relative humidity and temperature probes, a scanning mobility particle sizer spectrometer, an aerodynamic particle sizer spectrometer, a gas chromatograph-mass spectrometer, an integrating nephelometer, and a Fourier transform infrared spectrophotometer equipped with a long path (64 m) cell. Particles collected with impactors and filters at the various sampling ports can be analyzed subsequently by a variety of techniques. Formation of secondary organic aerosol from α-pinene reactions (NOx photooxidation and ozonolysis) are used to demonstrate the capabilities of this new system.

  1. Aerosol identification using a hybrid active/passive system

    NASA Astrophysics Data System (ADS)

    D'Amico, Francis M.; Moon, Raphael P.; Davidson, Charles E.

    2005-08-01

    Recent experimental work has shown that passive systems such as hyperspectral FTIR and frequency-tunable IR cameras have application in detection of biological aerosols. This provided the motivation for a new detection technique, which we call Aerosol Ranging Spectroscopy (ARS), whereby a scattering LIDAR is used to augment passive spectrometer data to determine the location and optical depth of the aerosol plume. When the two systems are co-aligned or boresighted, the hybrid data product provides valuable enhancements for signal exploitation of the passive spectral data. This paper presents the motivation and theoretical basis for the ARS technique. A prototype implementation of an ARS system will also be described, along with preliminary results from recent outdoor field experiments.

  2. Atmospheric aerosol profiling with a bistatic imaging lidar system.

    PubMed

    Barnes, John E; Sharma, N C Parikh; Kaplan, Trevor B

    2007-05-20

    Atmospheric aerosols have been profiled using a simple, imaging, bistatic lidar system. A vertical laser beam is imaged onto a charge-coupled-device camera from the ground to the zenith with a wide-angle lens (CLidar). The altitudes are derived geometrically from the position of the camera and laser with submeter resolution near the ground. The system requires no overlap correction needed in monostatic lidar systems and needs a much smaller dynamic range. Nighttime measurements of both molecular and aerosol scattering were made at Mauna Loa Observatory. The CLidar aerosol total scatter compares very well with a nephelometer measuring at 10 m above the ground. The results build on earlier work that compared purely molecular scattered light to theory, and detail instrument improvements. PMID:17514239

  3. Evaluations of tropospheric aerosol properties simulated by the community earth system model with a sectional aerosol microphysics scheme

    NASA Astrophysics Data System (ADS)

    Yu, Pengfei; Toon, Owen B.; Bardeen, Charles G.; Mills, Michael J.; Fan, Tianyi; English, Jason M.; Neely, Ryan R.

    2015-06-01

    A sectional aerosol model (CARMA) has been developed and coupled with the Community Earth System Model (CESM1). Aerosol microphysics, radiative properties, and interactions with clouds are simulated in the size-resolving model. The model described here uses 20 particle size bins for each aerosol component including freshly nucleated sulfate particles, as well as mixed particles containing sulfate, primary organics, black carbon, dust, and sea salt. The model also includes five types of bulk secondary organic aerosols with four volatility bins. The overall cost of CESM1-CARMA is approximately ˜2.6 times as much computer time as the standard three-mode aerosol model in CESM1 (CESM1-MAM3) and twice as much computer time as the seven-mode aerosol model in CESM1 (CESM1-MAM7) using similar gas phase chemistry codes. Aerosol spatial-temporal distributions are simulated and compared with a large set of observations from satellites, ground-based measurements, and airborne field campaigns. Simulated annual average aerosol optical depths are lower than MODIS/MISR satellite observations and AERONET observations by ˜32%. This difference is within the uncertainty of the satellite observations. CESM1/CARMA reproduces sulfate aerosol mass within 8%, organic aerosol mass within 20%, and black carbon aerosol mass within 50% compared with a multiyear average of the IMPROVE/EPA data over United States, but differences vary considerably at individual locations. Other data sets show similar levels of comparison with model simulations. The model suggests that in addition to sulfate, organic aerosols also significantly contribute to aerosol mass in the tropical UTLS, which is consistent with limited data.

  4. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications

    PubMed Central

    Labiris, N R; Dolovich, M B

    2003-01-01

    As the end organ for the treatment of local diseases or as the route of administration for systemic therapies, the lung is a very attractive target for drug delivery. It provides direct access to disease in the treatment of respiratory diseases, while providing an enormous surface area and a relatively low enzymatic, controlled environment for systemic absorption of medications. As a major port of entry, the lung has evolved to prevent the invasion of unwanted airborne particles from entering into the body. Airway geometry, humidity, mucociliary clearance and alveolar macrophages play a vital role in maintaining the sterility of the lung and consequently are barriers to the therapeutic effectiveness of inhaled medications. In addition, a drug's efficacy may be affected by where in the respiratory tract it is deposited, its delivered dose and the disease it may be trying to treat. PMID:14616418

  5. Online Mapping Systems for Climate Data Delivery

    NASA Astrophysics Data System (ADS)

    Gray, S. T.; Nicholson, C. M.; Bergantino, A. R.

    2009-12-01

    Online, map-based applications have experienced an explosion in popularity over the past decade. The success of these systems is largely due to their ability to provide a spatial framework data exploration, and for the visual context (e.g., satellite images) they offer. Here we detail the development of a new online mapping system for Wyoming that will serve as a portal for the delivery of weather, climate, and water-related data for users across the state. While capitalizing on the success of previous online mapping efforts, this new system also highlights the potential for additional applications and functionality. Known as the Wyoming Internet Map Server (WyoIMS), the system brings together real-time observations and summary products from multiple federal agencies (NOAA-NWS, NRCS, USGS) to provide “one-stop-shopping” for key climatic datasets. Likewise this system is providing a platform for data delivery, archiving, and QC/QA as part of a new statewide hydroclimatic monitoring network. Moving beyond the simple transfer of data, this system also allows users to access information from resources that include state libraries and various databases that contain information related to climate and water resources. Users can, for example, select individual counties, watersheds, irrigation districts, or municipalities and download a wide range of documents and reports specific to those locations. On the whole, WyoIMS has become a catalyst for the development of new climate-related products, and a foundation for decision support with applications in water resources, wildlife management, and agriculture.

  6. Silk Electrogel Based Gastroretentive Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Wang, Qianrui

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

  7. IN SILLICO LOBAR MODELS OF HUMAN LUNGS FOR TARGETED DELIVERY OF AEROSOLIZED PHARMACEUTICALS

    EPA Science Inventory

    The identification of factors affecting the deposition patterns of aerosolized pharmaceuticals has important implications to medicine (e.g., inhalation therapy regimens) and toxicology (e.g., drug testing protocols). Airway morphology is a critical element of the process, influen...

  8. Atmospheric aerosol monitoring by an elastic Scheimpflug lidar system.

    PubMed

    Mei, Liang; Brydegaard, Mikkel

    2015-11-30

    This work demonstrates a new approach - Scheimpflug lidar - for atmospheric aerosol monitoring. The atmospheric backscattering echo of a high-power continuous-wave laser diode is received by a Newtonian telescope and recorded by a tilted imaging sensor satisfying the Scheimpflug condition. The principles as well as the lidar equation are discussed in details. A Scheimpflug lidar system operating at around 808 nm is developed and employed for continuous atmospheric aerosol monitoring at daytime. Localized emission, atmospheric variation, as well as the changes of cloud height are observed from the recorded lidar signals. The extinction coefficient is retrieved according to the slope method for a homogeneous atmosphere. This work opens up new possibilities of using a compact and robust Scheimpflug lidar system for atmospheric aerosol remote sensing. PMID:26698808

  9. The use of CpG-free plasmids to mediate persistent gene expression following repeated aerosol delivery of pDNA/PEI complexes.

    PubMed

    Davies, Lee A; Hyde, Stephen C; Nunez-Alonso, Graciela; Bazzani, Reto P; Harding-Smith, Rebekka; Pringle, Ian A; Lawton, Anna E; Abdullah, Syahril; Roberts, Thomas C; McCormick, Dominique; Sumner-Jones, Stephanie G; Gill, Deborah R

    2012-08-01

    Aerosol gene therapy offers great potential for treating acquired and inherited lung diseases. For treatment of chronic lung diseases such as cystic fibrosis, asthma and emphysema, non-viral gene therapy will likely require repeated administration to maintain transgene expression in slowly dividing, or terminally differentiated, lung epithelial cells. When complexed with plasmid DNA (pDNA), the synthetic polymer, 25 kDa branched Polyethylenimine (PEI), can be formulated for aerosol delivery to the lungs. We show that pDNA/PEI aerosol formulations can be repeatedly administered to airways of mice on at least 10 occasions with no detectable toxicity. Interestingly, peak reporter gene activity upon repeated delivery was significantly reduced by up to 75% compared with a single administration, despite similar pDNA lung deposition at each subsequent aerosol exposure. Although the precise mechanism of inhibition is unknown, it is independent of mouse strain, does not involve an immune response, and is mediated by PEI. Importantly, using a dosing interval of 56 days, delivery of a fourth-generation, CpG-free plasmid generated high-level, sustained transgene expression, which was further boosted at subsequent administrations. Together these data indicate that pDNA/PEI aerosol formulations offer a versatile platform for gene delivery to the lung resulting in sustained transgene expression suitable for treatment of chronic lung diseases. PMID:22575838

  10. Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung.

    PubMed

    Dolovich, M A

    2000-06-01

    A number of studies in the literature support the use of fine aerosols of drug, inhaled at low IFRs to target peripheral airways, with the objective of improving clinical responses to inhaled therapy (Fig. 8). Attempts have been made to separate response due to changes in total administered dose or the surface concentration of the dose from response due to changes in site of deposition--both are affected by the particle size of the aerosol, with IFR additionally influencing the latter. The tools for measuring dose and distribution have improved over the last 10-15 years, and thus we should expect greater accuracy in these measurements for assessing drug delivery to the lung. There are still issues, though, in producing radiolabeled (99m)technetium aerosols that are precise markers for the pharmaceutical product being tested and in quantitating absolute doses deposited in the lung. PET isotopes may provide the means for directly labelling a drug and perhaps can offer an alternative for making these measurements in the future, but deposition measurements should not be used in isolation; protocols should incorporate clinical tests to provide parallel therapeutic data in response to inhalation of the drug by the various patient populations being studied. PMID:10894453

  11. Turbomachine injection nozzle including a coolant delivery system

    DOEpatents

    Zuo, Baifang

    2012-02-14

    An injection nozzle for a turbomachine includes a main body having a first end portion that extends to a second end portion defining an exterior wall having an outer surface. A plurality of fluid delivery tubes extend through the main body. Each of the plurality of fluid delivery tubes includes a first fluid inlet for receiving a first fluid, a second fluid inlet for receiving a second fluid and an outlet. The injection nozzle further includes a coolant delivery system arranged within the main body. The coolant delivery system guides a coolant along at least one of a portion of the exterior wall and around the plurality of fluid delivery tubes.

  12. A telemedicine health care delivery system

    NASA Technical Reports Server (NTRS)

    Sanders, Jay H.

    1991-01-01

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

  13. 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.

  14. Fate of inhaled monoclonal antibodies after the deposition of aerosolized particles in the respiratory system.

    PubMed

    Guilleminault, L; Azzopardi, N; Arnoult, C; Sobilo, J; Hervé, V; Montharu, J; Guillon, A; Andres, C; Herault, O; Le Pape, A; Diot, P; Lemarié, E; Paintaud, G; Gouilleux-Gruart, V; Heuzé-Vourc'h, N

    2014-12-28

    Monoclonal antibodies (mAbs) are usually delivered systemically, but only a small proportion of the drug reaches the lung after intravenous injection. The inhalation route is an attractive alternative for the local delivery of mAbs to treat lung diseases, potentially improving tissue concentration and exposure to the drug while limiting passage into the bloodstream and adverse effects. Several studies have shown that the delivery of mAbs or mAb-derived biopharmaceuticals via the airways is feasible and efficient, but little is known about the fate of inhaled mAbs after the deposition of aerosolized particles in the respiratory system. We used cetuximab, an anti-EGFR antibody, as our study model and showed that, after its delivery via the airways, this mAb accumulated rapidly in normal and cancerous tissues in the lung, at concentrations twice those achieved after intravenous delivery, for early time points. The spatial distribution of cetuximab within the tumor was heterogeneous, as reported after i.v. injection. Pharmacokinetic (PK) analyses were carried out in both mice and macaques and showed aerosolized cetuximab bioavailability to be lower and elimination times shorter in macaques than in mice. Using transgenic mice, we showed that FcRn, a key receptor involved in mAb distribution and PK, was likely to make a greater contribution to cetuximab recycling than to the transcytosis of this mAb in the airways. Our results indicate that the inhalation route is potentially useful for the treatment of both acute and chronic lung diseases, to boost and ensure the sustained accumulation of mAbs within the lungs, while limiting their passage into the bloodstream. PMID:25451545

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

    PubMed Central

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

    2016-01-01

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

  16. Leadership Dynamics Promoting Systemic Reform for Inclusive Service Delivery

    ERIC Educational Resources Information Center

    Scanlan, Martin

    2009-01-01

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

  17. Effects of ramp-up of inspired airflow on in vitro aerosol dose delivery performance for certain dry powder inhalers.

    PubMed

    Ung, Keith T; Chan, Hak-Kim

    2016-03-10

    This study investigated the effect of airflow ramp-up on the dose delivery performance of seven dry powder inhalers, covering a broad range of powder formulations and powder dispersion mechanisms. In vitro performance tests were performed at a target pressure drop of 4kPa, using two inspiratory flow ramp-up conditions, representing slow and fast ramp-up of airflow, respectively. The fluidization of bulk powder and aerosol clearance from the inhaler was assessed by laser photometer evaluation of aerosol emission kinetics and measurement of the delivered dose (DD). The quality of aerosol dispersion (i.e. de-agglomeration) and associated lung targeting performance was assessed by measuring the total lung dose (TLD) using the Alberta idealized mouth-throat model. The ratio of DD and TLD under slow/fast ramp conditions was used as a metric to rank-order flow ramp effects. Test results show that the delivered dose is relatively unaffected by flow ramp (DD ratio ~1 for all dry powder inhalers). In contrast, the total lung dose showed significantly more variation as a function of flow ramp and inhaler type. Engineered (spray dried) powder formulations were associated with relatively high TLD (>50% of nominal dose) compared to lactose blend and agglomerate based formulations, which had a lower TLD (7-40% of nominal dose), indicative of less efficient targeting of the lung. The TLD for the Tobi Podhaler was the least influenced by flow ramp (TLD ratio ~1), while the TLD for the Asmanex Twisthaler was the most sensitive to flow ramp (TLD ratio ≪1). The relatively high sensitivity of the Asmanex Twisthaler to flow ramp is attributed to rapid aerosol clearance (from the inhaler) combined with a strong effect of flow-rate on particle de-agglomeration and resulting size distribution. PMID:26780380

  18. The Aerosol-Monsoon Climate System of Asia

    NASA Technical Reports Server (NTRS)

    Lau, William K. M.; Kyu-Myong, Kim

    2012-01-01

    In Asian monsoon countries such as China and India, human health and safety problems caused by air-pollution are worsening due to the increased loading of atmospheric pollutants stemming from rising energy demand associated with the rapid pace of industrialization and modernization. Meanwhile, uneven distribution of monsoon rain associated with flash flood or prolonged drought, has caused major loss of human lives, and damages in crop and properties with devastating societal impacts on Asian countries. Historically, air-pollution and monsoon research are treated as separate problems. However a growing number of recent studies have suggested that the two problems may be intrinsically intertwined and need to be studied jointly. Because of complexity of the dynamics of the monsoon systems, aerosol impacts on monsoons and vice versa must be studied and understood in the context of aerosol forcing in relationship to changes in fundamental driving forces of the monsoon climate system (e.g. sea surface temperature, land-sea contrast etc.) on time scales from intraseasonal variability (weeks) to climate change ( multi-decades). Indeed, because of the large contributions of aerosols to the global and regional energy balance of the atmosphere and earth surface, and possible effects of the microphysics of clouds and precipitation, a better understanding of the response to climate change in Asian monsoon regions requires that aerosols be considered as an integral component of a fully coupled aerosol-monsoon system on all time scales. In this paper, using observations and results from climate modeling, we will discuss the coherent variability of the coupled aerosol-monsoon climate system in South Asia and East Asia, including aerosol distribution and types, with respect to rainfall, moisture, winds, land-sea thermal contrast, heat sources and sink distributions in the atmosphere in seasonal, interannual to climate change time scales. We will show examples of how elevated

  19. Biomedical Imaging in Implantable Drug Delivery Systems

    PubMed Central

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

    2015-01-01

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

  20. A motion maintaining antibiotic delivery system.

    PubMed

    Lombardi, Adolph V; Karnes, Jonathan M; Berend, Keith R

    2007-06-01

    Two-stage radical debridement with implant removal, antibiotic therapy, and delayed reimplantation remains the treatment of choice for deep infection in total joint arthroplasty. Studies have shown that articulating vs static spacers better improve functional results, increase patient satisfaction, prevent bone loss, and facilitate reimplantation without increasing risk of infection. Articulating spacers fabricated from cement provide a vehicle for prolonged local delivery of antibiotics. We currently use a mold system for creating antibiotic-laden articulating cement spacers. Disposable femoral and tibial molds are injection-filled with low-viscosity cement vacuum mixed with 3.6 to 4.8 g of tobramycin or gentamicin and 3.0 to 4.0 g of vancomycin per 40-g unit and massaged to fill any voids. After curing, the temporary spacers are removed from the molds, trimmed smooth, and cemented loosely into the joint space. PMID:17570278

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

    PubMed

    Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta

    2016-01-01

    There is no doubt that controlled and pulsatile drug delivery system is an important challenge in medicine over the conventional drug delivery system in case of therapeutic efficacy. However, the conventional drug delivery systems often offer a limited by their inability to drug delivery which consists of systemic toxicity, narrow therapeutic window, complex dosing schedule for long term treatment etc. Therefore, there has been a search for the drug delivery system that exhibit broad enhancing activity for more drugs with less complication. More recently, some elegant study has noted that, a new type of micro-electrochemical system or MEMS-based drug delivery systems called microchip has been improved to overcome the problems related to conventional drug delivery. Moreover, micro-fabrication technology has enabled to develop the implantable controlled released microchip devices with improved drug administration and patient compliance. In this article, we have presented an overview of the investigations on the feasibility and application of microchip as an advanced drug delivery system. Commercial manufacturing materials and methods, related other research works and current advancement of the microchips for controlled drug delivery have also been summarized. PMID:24758139

  2. Ocular drug delivery systems: An overview

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

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

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

  4. Development of a drug delivery system for efficient alveolar delivery of a neutralizing monoclonal antibody to treat pulmonary intoxication to ricin.

    PubMed

    Respaud, Renaud; Marchand, Denis; Pelat, Thibaut; Tchou-Wong, Kam-Meng; Roy, Chad J; Parent, Christelle; Cabrera, Maria; Guillemain, Joël; Mac Loughlin, Ronan; Levacher, Eric; Fontayne, Alexandre; Douziech-Eyrolles, Laurence; Junqua-Moullet, Alexandra; Guilleminault, Laurent; Thullier, Philippe; Guillot-Combe, Emmanuelle; Vecellio, Laurent; Heuzé-Vourc'h, Nathalie

    2016-07-28

    The high toxicity of ricin and its ease of production have made it a major bioterrorism threat worldwide. There is however no efficient and approved treatment for poisoning by ricin inhalation, although there have been major improvements in diagnosis and therapeutic strategies. We describe the development of an anti-ricin neutralizing monoclonal antibody (IgG 43RCA-G1) and a device for its rapid and effective delivery into the lungs for an application in humans. The antibody is a full-length IgG and binds to the ricin A-chain subunit with a high affinity (KD=53pM). Local administration of the antibody into the respiratory tract of mice 6h after pulmonary ricin intoxication allowed the rescue of 100% of intoxicated animals. Specific operational constraints and aerosolization stresses, resulting in protein aggregation and loss of activity, were overcome by formulating the drug as a dry-powder that is solubilized extemporaneously in a stabilizing solution to be nebulized. Inhalation studies in mice showed that this formulation of IgG 43RCA-G1 did not induce pulmonary inflammation. A mesh nebulizer was customized to improve IgG 43RCA-G1 deposition into the alveolar region of human lungs, where ricin aerosol particles mostly accumulate. The drug delivery system also comprises a semi-automatic reconstitution system to facilitate its use and a specific holding chamber to maximize aerosol delivery deep into the lung. In vivo studies in monkeys showed that drug delivery with the device resulted in a high concentration of IgG 43RCA-G1 in the airways for at least 6h after local deposition, which is consistent with the therapeutic window and limited passage into the bloodstream. PMID:27173943

  5. Importance of novel drug delivery systems in herbal medicines.

    PubMed

    Devi, V Kusum; Jain, Nimisha; Valli, Kusum S

    2010-01-01

    Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drug delivery system used for administering the herbal medicine to the patient is traditional and out-of-date, resulting in reduced efficacy of the drug. If the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems. However, modern phytopharmaceutical research can solve the scientific needs (such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required etc.) of herbal medicines to be incorporated in novel drug delivery system, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. This article summarizes various drug delivery technologies, which can be used for herbal actives together with some examples. PMID:22228938

  6. Lifting options for stratospheric aerosol geoengineering: advantages of tethered balloon systems.

    PubMed

    Davidson, Peter; Burgoyne, Chris; Hunt, Hugh; Causier, Matt

    2012-09-13

    The Royal Society report 'Geoengineering the Climate' identified solar radiation management using albedo-enhancing aerosols injected into the stratosphere as the most affordable and effective option for geoengineering, but did not consider in any detail the options for delivery. This paper provides outline engineering analyses of the options, both for batch-delivery processes, following up on previous work for artillery shells, missiles, aircraft and free-flying balloons, as well as a more lengthy analysis of continuous-delivery systems that require a pipe connected to the ground and supported at a height of 20 km, either by a tower or by a tethered balloon. Towers are shown not to be practical, but a tethered balloon delivery system, with high-pressure pumping, appears to have much lower operating and capital costs than all other delivery options. Instead of transporting sulphuric acid mist precursors, such a system could also be used to transport slurries of high refractive index particles such as coated titanium dioxide. The use of such particles would allow useful experiments on opacity, coagulation and atmospheric chemistry at modest rates so as not to perturb regional or global climatic conditions, thus reducing scale-up risks. Criteria for particle choice are discussed, including the need to minimize or prevent ozone destruction. The paper estimates the time scales and relatively modest costs required if a tethered balloon system were to be introduced in a measured way with testing and development work proceeding over three decades, rather than in an emergency. The manufacture of a tether capable of sustaining the high tensions and internal pressures needed, as well as strong winds, is a significant challenge, as is the development of the necessary pumping and dispersion technologies. The greatest challenge may be the manufacture and launch of very large balloons, but means have been identified to significantly reduce the size of such balloons or aerostats

  7. A novel micropump droplet generator for aerosol drug delivery: Design simulations

    PubMed Central

    Su, Guoguang; Longest, P. Worth; Pidaparti, Ramana M.

    2010-01-01

    One challenge of generating a liquid aerosol is finding an efficient way to break up bulk amounts of the compound into micron-sized droplets. Traditional methods of aerosol generation focus on the principle of creating the liquid droplets by blowing air at high speed over or through a liquid. In this study, a novel micropump droplet generator (MDG) is proposed based on a microfluidics device to produce monodisperse droplets on demand (DoD). The micropump design was employed to both pump the fluid into the air and to encourage droplet breakup and aerosol formation. Computational simulation modeling of the new MDG was developed and validated with comparisons to experimental data for current generators. The device was found to produce an aerosol similar to a vibrating orifice DoD device. Most importantly, the input power required by the newly proposed device (MDG) was several orders of magnitude below existing DoD generators for a similar droplet output. Based on the simulation results obtained in comparison with current DoD generators, the MDG device performed effectively at higher frequencies, smaller nozzle diameters, and regardless of the liquid viscosity of the solution. PMID:21151580

  8. Micro injector sample delivery system for charged molecules

    DOEpatents

    Davidson, James C.; Balch, Joseph W.

    1999-11-09

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

  9. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

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

    2012-01-01

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

  10. Ariadne: The Next Generation of Electronic Document Delivery Systems.

    ERIC Educational Resources Information Center

    Roes, Hans; Dijkstra, Joost

    1994-01-01

    Describes an approach to electronic document delivery which has evolved at Tilburg University (Netherlands), leading to the development of a system called Ariadne. Highlights include various generations of electronic document delivery systems; standards, including the work of the Group on Electronic Document Interchange; and a description of the…

  11. New Delivery Systems for the 21st Century.

    ERIC Educational Resources Information Center

    Van Patten, James J.

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

  12. Guidelines for Psychological Practice in Health Care Delivery Systems

    ERIC Educational Resources Information Center

    American Psychologist, 2013

    2013-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  15. Delivery of anthropogenic bioavailable iron from mineral dust and combustion aerosols to the ocean

    NASA Astrophysics Data System (ADS)

    Ito, A.; Shi, Z.

    2016-01-01

    Atmospheric deposition of anthropogenic soluble iron (Fe) to the ocean has been suggested to modulate primary ocean productivity and thus indirectly affect the climate. A key process contributing to anthropogenic sources of soluble Fe is associated with air pollution, which acidifies Fe-containing mineral aerosols during their transport and leads to Fe transformation from insoluble to soluble forms. However, there is large uncertainty in our estimate of this anthropogenic soluble Fe. In this study, for the first time, we interactively combined laboratory kinetic experiments with global aerosol modeling to more accurately quantify anthropogenic soluble Fe due to air pollution. Firstly, we determined Fe dissolution kinetics of African dust samples at acidic pH values with and without ionic species commonly found in aerosol water (i.e., sulfate and oxalate). Then, by using acidity as a master variable, we constructed a new empirical scheme for Fe release from mineral dust due to inorganic and organic anions in aerosol water. We implemented this new scheme and applied an updated mineralogical emission database in a global atmospheric chemistry transport model to estimate the atmospheric concentration and deposition flux of soluble Fe under preindustrial and modern conditions. Our improved model successfully captured the inverse relationship of Fe solubility and total Fe loading measured over the North Atlantic Ocean (i.e., 1-2 orders of magnitude lower Fe solubility in northern-African- than combustion-influenced aerosols). The model results show a positive relationship between Fe solubility and water-soluble organic carbon (WSOC)/Fe molar ratio, which is consistent with previous field measurements. We estimated that deposition of soluble Fe to the ocean increased from 0.05-0.07 Tg Fe yr-1 in the preindustrial era to 0.11-0.12 Tg Fe yr-1 in the present day, due to air pollution. Over the high-nitrate, low-chlorophyll (HNLC) regions of the ocean, the modeled Fe

  16. Delivery of anthropogenic bioavailable iron from mineral dust and combustion aerosols to the ocean

    NASA Astrophysics Data System (ADS)

    Ito, A.; Shi, Z.

    2015-08-01

    Atmospheric deposition of anthropogenic soluble iron (Fe) to the ocean has been suggested to modulate primary ocean productivity and thus indirectly affect the climate. A key process contributing to anthropogenic sources of soluble Fe is associated with air pollution, which acidifies Fe-containing mineral aerosols during their transport and leads to Fe transformation from insoluble to soluble forms. However, there is large uncertainty in our estimate of this anthropogenic soluble Fe. Here, we, for the first time, interactively combined laboratory kinetic experiments with global aerosol modeling to more accurately quantify anthropogenic soluble Fe due to air pollution. We firstly examined Fe dissolution kinetics of African dust samples at acidic pH values with and without ionic species commonly found in aerosol water (i.e., sulfate and oxalate). We then constructed a new empirical scheme for Fe release from mineral dust due to inorganic and organic anions in aerosol water, by using acidity as a master variable. We implemented this new scheme and applied an updated mineralogical emission database in a global atmospheric chemistry transport model to estimate the atmospheric concentration and deposition flux of soluble Fe under preindustrial and modern conditions. Our improved model successfully captured the inverse relationship of Fe solubility and total Fe loading measured over the North Atlantic Ocean (i.e., 1-2 orders of magnitude lower Fe solubility in North African- than combustion-influenced aerosols). The model results show a positive relationship between Fe solubility and water soluble organic carbon (WSOC)/Fe molar ratio, which is consistent with previous field measurements. We estimated that deposition of soluble Fe to the ocean increased from 0.05-0.07 Tg Fe yr-1 in preindustrial era to 0.11-0.12 Tg Fe yr-1 in present days, due to air pollution. Over the High Nitrate Low Chlorophyll (HNLC) regions of the ocean, the modeled Fe solubility remains low for

  17. The Controlled Drug Delivery Systems: Past Forward and Future Back

    PubMed Central

    Park, Kinam

    2014-01-01

    The controlled drug delivery technology has progressed over the last six decades. It began in 1952 with the introduction of the first sustained release formulation. The 1st generation (1950-1980) of drug delivery was focused on developing oral and transdermal sustained release systems and establishing the controlled drug release mechanisms. Attention of the 2nd generation (1980-2010) was dedicated to development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was consumed mostly for studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role during the 2nd generation of drug delivery technologies, and it will continue playing a leading role for the next generation. Taking the right path towards the productive 3rd generation of drug delivery technologies requires honest open dialogues without any preconceived ideas of the past. The drug delivery field needs to take a bold approach of designing the future drug delivery formulations first, based on today’s necessities, and produce necessary innovations. The JCR will provide the forum for sharing the new ideas that will shape the 3rd generation of drug delivery technologies. PMID:24794901

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

    PubMed Central

    Mok, Hyejung; Zhang, Miqin

    2014-01-01

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

  19. CLIPS: An expert system tool for delivery and training

    NASA Technical Reports Server (NTRS)

    Riley, Gary; Culbert, Chris; Savely, Robert T.; Lopez, Frank

    1987-01-01

    The C Language Integrated Production System (CLIPS) is a forward chaining rule-based language. The requirements necessary for an expert system tool which is used for development, delivery, and training are examined. Because of its high portability, low cost, and ease of integration with external systems, CLIPS has great potential as an expert system tool for delivery and training. In addition, its representation flexibility, debugging aids, and performance, along with its other strengths, make it a viable alternative for expert system development.

  20. Marine Origin Polysaccharides in Drug Delivery Systems.

    PubMed

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

    2016-02-01

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

  1. Marine Origin Polysaccharides in Drug Delivery Systems

    PubMed Central

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

    2016-01-01

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

  2. A Search for Correlations Between Four Different Atmospheric Aerosol Measurement Systems Atop Rattlesnake Mountain, Washington

    NASA Astrophysics Data System (ADS)

    Milbrath, Brian

    2004-05-01

    Accurate atmospheric aerosol transport measurements are important to international nuclear test monitoring, emergency response, health and ecosystem toxicology, and climate change. An International Monitoring System (IMS) is being established which will include a suite of aerosol radionuclide sensors. To explore the possibility of using the IMS sites to improve the understanding of global atmospheric aerosol transport, four state-of-the-art aerosol measurement systems were placed atop Rattlesnake Mountain at Pacific Northwest National Laboratory. The Radionuclide Aerosol Sampler/Analyzer measures radionuclide concentration via gamma-ray spectroscopy. The Cascade Impactor Beam Analyzer Technique measures 30 elements in three aerosol sizes using PNNLâ's Ion Beams Materials Analysis Laboratory. The Tapered Element Oscillating Microbalance provides time-averaged aerosol mass concentrations for a range of sizes. The Multi-Filter Rotating Shadowband Radiometer measures the solar irradiance to derive an aerosol optical depth. Results and correlations from the four different detectors will be presented.

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

    PubMed Central

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

    2016-01-01

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

  4. Recent Challenges in Insulin Delivery Systems: A Review

    PubMed Central

    Al-Tabakha, M. M.; Arida, A. I.

    2008-01-01

    Relatively, a large percentage of world population is affected by diabetes mellitus, out of which approximately 5-10% with type 1 diabetes while the remaining 90% with type 2. Insulin administration is essential for type 1 patients while it is required at later stage by the patients of type 2. Current insulin delivery systems are available as transdermal injections which may be considered as invasive. Several non-invasive approaches for insulin delivery are being pursued by pharmaceutical companies to reduce the pain, and hypoglycemic incidences associated with injections in order to improve patient compliance. While any new insulin delivery system requires health authorities' approval, to provide long term safety profile and insuring patients' acceptance. The inhalation delivery system Exubera® has already become clinically available in the United States and Europe for patients with diabetes as non-invasive delivery system. PMID:20046733

  5. Guidance to employers on integrating e-cigarettes/electronic nicotine delivery systems into tobacco worksite policy.

    PubMed

    Whitsel, Laurie P; Benowitz, Neal; Bhatnagar, Aruni; Bullen, Chris; Goldstein, Fred; Matthias-Gray, Lena; Grossmeier, Jessica; Harris, John; Isaac, Fikry; Loeppke, Ron; Manley, Marc; Moseley, Karen; Niemiec, Ted; OʼBrien, Vince; Palma-Davis, LaVaughn; Pronk, Nico; Pshock, Jim; Stave, Gregg M; Terry, Paul

    2015-03-01

    In recent years, new products have entered the marketplace that complicate decisions about tobacco control policies and prevention in the workplace. These products, called electronic cigarettes (e-cigarettes) or electronic nicotine delivery systems, most often deliver nicotine as an aerosol for inhalation, without combustion of tobacco. This new mode of nicotine delivery raises several questions about the safety of the product for the user, the effects of secondhand exposure, how the public use of these products should be handled within tobacco-free and smoke-free air policies, and how their use affects tobacco cessation programs, wellness incentives, and other initiatives to prevent and control tobacco use. In this article, we provide a background on e-cigarettes and then outline key policy recommendations for employers on how the use of these new devices should be managed within worksite tobacco prevention programs and control policies. PMID:25742539

  6. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    PubMed

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

    2015-09-15

    This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. PMID:25683694

  7. New apparatus of single particle trap system for aerosol visualization

    NASA Astrophysics Data System (ADS)

    Higashi, Hidenori; Fujioka, Tomomi; Endo, Tetsuo; Kitayama, Chiho; Seto, Takafumi; Otani, Yoshio

    2014-08-01

    Control of transport and deposition of charged aerosol particles is important in various manufacturing processes. Aerosol visualization is an effective method to directly observe light scattering signal from laser-irradiated single aerosol particle trapped in a visualization cell. New single particle trap system triggered by light scattering pulse signal was developed in this study. The performance of the device was evaluated experimentally. Experimental setup consisted of an aerosol generator, a differential mobility analyzer (DMA), an optical particle counter (OPC) and the single particle trap system. Polystylene latex standard (PSL) particles (0.5, 1.0 and 2.0 μm) were generated and classified according to the charge by the DMA. Singly charged 0.5 and 1.0 μm particles and doubly charged 2.0 μm particles were used as test particles. The single particle trap system was composed of a light scattering signal detector and a visualization cell. When the particle passed through the detector, trigger signal with a given delay time sent to the solenoid valves upstream and downstream of the visualization cell for trapping the particle in the visualization cell. The motion of particle in the visualization cell was monitored by CCD camera and the gravitational settling velocity and the electrostatic migration velocity were measured from the video image. The aerodynamic diameter obtained from the settling velocity was in good agreement with Stokes diameter calculated from the electrostatic migration velocity for individual particles. It was also found that the aerodynamic diameter obtained from the settling velocity was a one-to-one function of the scattered light intensity of individual particles. The applicability of this system will be discussed.

  8. A portable optical particle counter system for measuring dust aerosols.

    PubMed

    Marple, V A; Rubow, K L

    1978-03-01

    A portable battery-operated optical particle counter/multichannel analyzer system has been developed for the numbers size distribution and number concentration measurement of light-absorbing irregular-shaped dust particles. An inertial impactor technique has been used to obtain calibration curves by relating the magnitude of the optical counter's signal to the particle's aerodynamic or Stokes' diameter. These calibrations have been made for aerosols of coal, potash, silica, rock (copper ore), and Arizona road dust particles. PMID:645547

  9. The LITA Drill and Sample Delivery System

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  10. [Recent trends on clinical development of oral insulin delivery systems].

    PubMed

    Takeda-Morishita, Mariko

    2015-12-01

    Great effort for developing effective needle-free insulin delivery technology, especially oral delivery, has been continued in worldwide, indeed, from the era of insulin discovered. Oral administration of insulin would offer not only the potential for improved patient compliance but also improved safety/efficacy in certain instances. Much effort for developing noninvasive delivery systems of insulin has been done, and recently, several promising insulin oral formulations are entered into clinical trials. Delivering insulin in orally was major challenge, but its realization is surely approaching. This review provides an update on recent approaches that have shown promise in insulin oral delivery systems. In addition, the progress of basic research in noninvasive delivery system research for biopharmaceuticals is discussed. PMID:26666165

  11. Optical diagnostics integrated with laser spark delivery system

    DOEpatents

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

    2008-09-02

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

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

    PubMed

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

    2009-01-01

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

  13. Auto-associative amphiphilic polysaccharides as drug delivery systems.

    PubMed

    Hassani, Leila N; Hendra, Frédéric; Bouchemal, Kawthar

    2012-06-01

    Self-assembly of amphiphilic polysaccharides provides a positive outlook for drug delivery systems without the need for solvents or surfactants. Various polymeric amphiphilic polysaccharides undergo intramolecular or intermolecular associations in water. This type of association, promoted by hydrophobic segments, led to the formation of various drug delivery systems such as micelles, nanoparticles, liposomes and hydrogels. Here, we review a selection of the most important amphiphilic polysaccharides used as drug delivery systems and their pharmaceutical applications. Attention focuses on amphiphilic chitosan owing to its unique properties such as excellent biocompatibility, non-toxicity and antimicrobial and bioadhesive properties. PMID:22305936

  14. Delivery system for molten salt oxidation of solid waste

    DOEpatents

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

    2002-01-01

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

  15. Design, Characterization, and Aerosol Dispersion Performance Modeling of Advanced Spray-Dried Microparticulate/Nanoparticulate Mannitol Powders for Targeted Pulmonary Delivery as Dry Powder Inhalers

    PubMed Central

    Li, Xiaojian; Vogt, Frederick G.; Hayes, Don

    2014-01-01

    Abstract Background: The purpose was to design and characterize inhalable microparticulate/nanoparticulate dry powders of mannitol with essential particle properties for targeted dry powder delivery for cystic fibrosis mucolytic treatment by dilute organic solution spray drying, and, in addition, to tailor and correlate aerosol dispersion performance delivered as dry powder inhalers based on spray-drying conditions and solid-state physicochemical properties. Methods: Organic solution advanced spray drying from dilute solution followed by comprehensive solid-state physicochemical characterization and in vitro dry powder aerosolization were used. Results: The particle size distribution of the spray-dried (SD) powders was narrow, unimodal, and in the range of ∼500 nm to 2.0 μm. The particles possessed spherical particle morphology, relatively smooth surface morphology, low water content and vapor sorption (crystallization occurred at exposure above 65% relative humidity), and retention of crystallinity by polymorphic interconversion. The emitted dose, fine particle fraction (FPF), and respirable fraction (RF) were all relatively high. The mass median aerodynamic diameters were below 4 μm for all SD mannitol aerosols. Conclusion: The in vitro aerosol deposition stage patterns could be tailored based on spray-drying pump rate. Positive linear correlation was observed between both FPF and RF values with spray-drying pump rates. The interplay between various spray-drying conditions, particle physicochemical properties, and aerosol dispersion performance was observed and examined, which enabled tailoring and modeling of high aerosol deposition patterns. PMID:24502451

  16. CHAPTER 11. DELIVERY AND DISTRIBUTION SYSTEMS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water delivery through canals or pipelines usually implies that several farms must somehow share access to the water in terms of flow rate, duration of access, and the return time to access the flow again, called an irrigation schedule, which can be rigid or flexible regarding the rate, duration and...

  17. Microneedles As a Delivery System for Gene Therapy

    PubMed Central

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

    2016-01-01

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

  18. Microneedles As a Delivery System for Gene Therapy.

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  20. Systems engineering tradeoffs for a bio-aerosol lidar referee system

    NASA Astrophysics Data System (ADS)

    Warren, Jeffery W.; Thomas, Michael E.; Rogala, Eric W.; Maret, Arthur R.; Schumacher, Camille A.; Diaz, Antonio

    2004-08-01

    Analytical results and tradeoffs are reported for an aerosol lidar system that is intended to serve as a referee during testing of standoff bio-aerosol detection systems. The lidar system is still under development by Dugway Proving Grounds -- results from the operational system are not included in this paper. The recommended configuration of the lidar system is to use a 1064 nm lidar in elastic mode to measure the concentration of the aerosol, and a 355 nm excitation to measure the fluorescence of the bio-aerosol. Both of these measurements are important in scoring the performance of the systems that will be tested at DPG. Performance tradeoffs and predictions are presented primarily for the elastic mode lidar. The elastic mode lidar is designed to make measurements out to ranges of approximately 15 km. The UV fluorescence mode of operation is intended to support discrimination of bio-aerosols from non-biological aerosols, and is only required to operate at a range of 1 km. The optical design of the proposed telescope supports dual wavelength operation, allows for effective TV camera imaging for test and alignment support, and tailors the optical overlap function for the UV and near IR lidar to optimize the performance of both subsystems.

  1. Measurements of Atmospheric Aerosol Vertical Distributions above Svalbard, Norway using Unmanned Aerial Systems (UAS)

    NASA Astrophysics Data System (ADS)

    Bates, T. S.; Johnson, J. E.; Stalin, S.; Telg, H.; Murphy, D. M.; Burkhart, J. F.; Quinn, P.; Storvold, R.

    2015-12-01

    Atmospheric aerosol vertical distributions were measured above Svalbard, Norway in April 2015 to investigate the processes controlling aerosol concentrations and radiative effects. The aerosol payload was flown in a NOAA/PMEL MANTA Unmanned Aerial System (UAS) on 9 flights totaling 19 flight hours. Measurements were made of particle number concentration and aerosol light absorption at three wavelengths, similar to those conducted in April 2011 (Bates et al., Atmos. Meas. Tech., 6, 2115-2120, 2013). A filter sample was collected on each flight for analyses of trace elements. Additional measurements in the aerosol payload in 2015 included aerosol size distributions obtained using a Printed Optical Particle Spectrometer (POPS) and aerosol optical depth obtained using a four wavelength miniature Scanning Aerosol Sun Photometer (miniSASP). The data show most of the column aerosol mass and resulting optical depth in the boundary layer but frequent aerosol layers aloft with high particle number concentration (2000 cm-3) and enhanced aerosol light absorption (1 Mm-1). Transport of these aerosol layers was assessed using FLEXPART particle dispersion models. The data contribute to an assessment of sources of BC to the Arctic and potential climate impacts.

  2. Effects of aerosol on evaporation, freezing and precipitation in a multiple cloud system

    NASA Astrophysics Data System (ADS)

    Lee, Seoung Soo; Kim, Byung-Gon; Yum, Seong Soo; Seo, Kyong-Hwan; Jung, Chang-Hoon; Um, Jun Shik; Li, Zhanqing; Hong, JinKyu; Chang, Ki-Ho; Jeong, Jin-Yim

    2016-04-01

    Aerosol effects on clouds and precipitation account for a large portion of uncertainties in the prediction of the future course of global hydrologic circulations and climate. As a process of a better understanding of interactions between aerosol, clouds and precipitation, simulations are performed for a mixed-phase convective multiple-cloud system over the tropics. Studies on single-cloud systems have shown that aerosol-induced increases in freezing, associated increases in parcel buoyancy and thus the intensity of clouds (or updrafts) are a main mechanism which controls aerosol-cloud-precipitation interactions in convective clouds. However, in the multiple-cloud system that plays much more important roles in global hydrologic circulations and thus climate than single-cloud systems, aerosol effects on condensation play the most important role in aerosol-induced changes in the intensity of clouds and the effects on freezing play a negligible role in those changes. Aerosol-induced enhancement in evaporation intensifies gust fronts and increases the number of subsequently developing clouds, which leads to the substantial increases in condensation and associated intensity of convection. Although aerosol-induced enhancement in freezing takes part in the increases in condensation by inducing stronger convergence around cloud bottom, the increases in condensation are ~one order of magnitude larger than those in freezing. It is found that while aerosol-induced increases in freezing create intermittent extremely heavy precipitation, aerosol-induced increases in evaporation enhance light and medium precipitation in the multiple-cloud system here. This increase in light and medium precipitation makes it possible that cumulative precipitation increases with increasing aerosol concentration, although the increase is small. It is interesting that the altitude of the maximum of the time- and domain-averaged hydrometeor mass densities is quite robust to increases in aerosol

  3. Aerosol observing system platform integration and AAF instrumentation

    SciTech Connect

    Springston, S.; Sedlacek, A.

    2010-03-15

    As part of the federal government’s 2009 American Recovery and Reinvestment Act (ARRA), the U.S. DOE Office of Science allocated funds for the capital upgrade of the Atmospheric Radiation Measurement (ARM) Climate Research Facility to improve and expand observational capabilities related to cloud and aerosol properties. The ARM Facility was established as a national user facility for the global scientific community to conduct a wide range of interdisciplinary science. Part of the ARRA-funded expansion of the ARM Facility includes four new Aerosol Observing Systems (AOS) to be designed, instrumented, and mentored by BNL. The enclosures will be customized SeaTainers. These new platforms ([AMF2]: ARM Mobile Facility-2; [TWP-D]: Tropical Western Pacific at Darwin; and [MAOS-A]/[MAOS-C]: Mobile Aerosol Observing System-Aerosol/-Chemistry) will provide a laboratory environment for fielding instruments to collect data on aerosol life cycle, microphysics, and optical/physical properties. The extensive instrument suite includes both established methods and initial deployments of new techniques to add breadth and depth to the AOS data sets. The platforms are designed: (1) to have all instruments pre-installed before deployment, allowing a higher measurement duty cycle; (2) with a standardized configuration improving the robustness of data inter-comparability; (3) to provide remote access capability for instrument mentors; and (4) to readily accommodate guest instrumentation. The first deployment of the AMF2 platform will be at the upcoming StormVEx campaign held at Steamboat Springs, Colorado, October 15, 2010–March 31, 2011 while the TWP-D AOS will be stationed at the ARM Darwin site. The maiden deployments of the MAOS-A and MAOS-C platforms will be during the Ganges Valley Experiment (GVAX) scheduled for April 2011–April 2012. In addition to the ground-based AOS platforms, thee major instrument builds for the AAF are also being undertaken (new trace gas package [NO

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

    PubMed Central

    Meng, Ellis; Hoang, Tuan

    2013-01-01

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

  5. The Multi-Sensor Aerosol Products Sampling System (MAPSS) for Integrated Analysis of Satellite Retrieval Uncertainties

    NASA Technical Reports Server (NTRS)

    Ichoku, Charles; Petrenko, Maksym; Leptoukh, Gregory

    2010-01-01

    Among the known atmospheric constituents, aerosols represent the greatest uncertainty in climate research. Although satellite-based aerosol retrieval has practically become routine, especially during the last decade, there is often disagreement between similar aerosol parameters retrieved from different sensors, leaving users confused as to which sensors to trust for answering important science questions about the distribution, properties, and impacts of aerosols. As long as there is no consensus and the inconsistencies are not well characterized and understood ', there will be no way of developing reliable climate data records from satellite aerosol measurements. Fortunately, the most globally representative well-calibrated ground-based aerosol measurements corresponding to the satellite-retrieved products are available from the Aerosol Robotic Network (AERONET). To adequately utilize the advantages offered by this vital resource,., an online Multi-sensor Aerosol Products Sampling System (MAPSS) was recently developed. The aim of MAPSS is to facilitate detailed comparative analysis of satellite aerosol measurements from different sensors (Terra-MODIS, Aqua-MODIS, Terra-MISR, Aura-OMI, Parasol-POLDER, and Calipso-CALIOP) based on the collocation of these data products over AERONET stations. In this presentation, we will describe the strategy of the MAPSS system, its potential advantages for the aerosol community, and the preliminary results of an integrated comparative uncertainty analysis of aerosol products from multiple satellite sensors.

  6. Silk-based delivery systems of bioactive molecules

    PubMed Central

    Numata, Keiji; Kaplan, David L

    2010-01-01

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

  7. Endogenous lung surfactant inspired pH responsive nanovesicle aerosols: Pulmonary compatible and site-specific drug delivery in lung metastases

    NASA Astrophysics Data System (ADS)

    Joshi, Nitin; Shirsath, Nitesh; Singh, Ankur; Joshi, Kalpana S.; Banerjee, Rinti

    2014-11-01

    Concerns related to pulmonary toxicity and non-specificity of nanoparticles have limited their clinical applications for aerosol delivery of chemotherapeutics in lung cancer. We hypothesized that pulmonary surfactant mimetic nanoparticles that offer pH responsive release specifically in tumor may be a possible solution to overcome these issues. We therefore developed lung surfactant mimetic and pH responsive lipid nanovesicles for aerosol delivery of paclitaxel in metastatic lung cancer. 100-200 nm sized nanovesicles showed improved fusogenicity and cytosolic drug release, specifically with cancer cells, thereby resulting in improved cytotoxicity of paclitaxel in B16F10 murine melanoma cells and cytocompatibility with normal lung fibroblasts (MRC 5). The nanovesicles showed airway patency similar to that of endogenous pulmonary surfactant and did not elicit inflammatory response in alveolar macrophages. Their aerosol administration while significantly improving the biodistribution of paclitaxel in comparison to Taxol (i.v.), also showed significantly higher metastastes inhibition (~75%) in comparison to that of i.v. Taxol and i.v. Abraxane. No signs of interstitial pulmonary fiborisis, chronic inflammation and any other pulmonary toxicity were observed with nanovesicle formulation. Overall, these nanovesicles may be a potential platform to efficiently deliver hydrophobic drugs as aerosol in metastatic lung cancer and other lung diseases, without causing pulmonary toxicity.

  8. Endogenous lung surfactant inspired pH responsive nanovesicle aerosols: pulmonary compatible and site-specific drug delivery in lung metastases.

    PubMed

    Joshi, Nitin; Shirsath, Nitesh; Singh, Ankur; Joshi, Kalpana S; Banerjee, Rinti

    2014-01-01

    Concerns related to pulmonary toxicity and non-specificity of nanoparticles have limited their clinical applications for aerosol delivery of chemotherapeutics in lung cancer. We hypothesized that pulmonary surfactant mimetic nanoparticles that offer pH responsive release specifically in tumor may be a possible solution to overcome these issues. We therefore developed lung surfactant mimetic and pH responsive lipid nanovesicles for aerosol delivery of paclitaxel in metastatic lung cancer. 100-200 nm sized nanovesicles showed improved fusogenicity and cytosolic drug release, specifically with cancer cells, thereby resulting in improved cytotoxicity of paclitaxel in B16F10 murine melanoma cells and cytocompatibility with normal lung fibroblasts (MRC 5). The nanovesicles showed airway patency similar to that of endogenous pulmonary surfactant and did not elicit inflammatory response in alveolar macrophages. Their aerosol administration while significantly improving the biodistribution of paclitaxel in comparison to Taxol (i.v.), also showed significantly higher metastastes inhibition (~75%) in comparison to that of i.v. Taxol and i.v. Abraxane. No signs of interstitial pulmonary fiborisis, chronic inflammation and any other pulmonary toxicity were observed with nanovesicle formulation. Overall, these nanovesicles may be a potential platform to efficiently deliver hydrophobic drugs as aerosol in metastatic lung cancer and other lung diseases, without causing pulmonary toxicity. PMID:25403950

  9. Endogenous lung surfactant inspired pH responsive nanovesicle aerosols: Pulmonary compatible and site-specific drug delivery in lung metastases

    PubMed Central

    Joshi, Nitin; Shirsath, Nitesh; Singh, Ankur; Joshi, Kalpana S.; Banerjee, Rinti

    2014-01-01

    Concerns related to pulmonary toxicity and non-specificity of nanoparticles have limited their clinical applications for aerosol delivery of chemotherapeutics in lung cancer. We hypothesized that pulmonary surfactant mimetic nanoparticles that offer pH responsive release specifically in tumor may be a possible solution to overcome these issues. We therefore developed lung surfactant mimetic and pH responsive lipid nanovesicles for aerosol delivery of paclitaxel in metastatic lung cancer. 100–200 nm sized nanovesicles showed improved fusogenicity and cytosolic drug release, specifically with cancer cells, thereby resulting in improved cytotoxicity of paclitaxel in B16F10 murine melanoma cells and cytocompatibility with normal lung fibroblasts (MRC 5). The nanovesicles showed airway patency similar to that of endogenous pulmonary surfactant and did not elicit inflammatory response in alveolar macrophages. Their aerosol administration while significantly improving the biodistribution of paclitaxel in comparison to Taxol (i.v.), also showed significantly higher metastastes inhibition (~75%) in comparison to that of i.v. Taxol and i.v. Abraxane. No signs of interstitial pulmonary fiborisis, chronic inflammation and any other pulmonary toxicity were observed with nanovesicle formulation. Overall, these nanovesicles may be a potential platform to efficiently deliver hydrophobic drugs as aerosol in metastatic lung cancer and other lung diseases, without causing pulmonary toxicity. PMID:25403950

  10. Assessment of regional effects in pulmonary aerosol delivery using Direct Numerical Simulation (DNS)

    NASA Astrophysics Data System (ADS)

    Kassinos, Stavros; Stylianou, Fotos; Koullapis, Pantelis; UCY-Compsci Team

    2014-11-01

    Recent computational studies have shown that the airflow in the upper human airways is turbulent during much of the respiratory cycle. One of the features of respiratory airflow that poses a challenge to computations based on Reynolds-Averaged Navier-Stokes (RANS) closures is the laminar-turbulent-laminar transition as the flow moves from the mouth through the glottis and down to the lower conducting airways. Turbulence and unsteadiness are expected at least through the first few bifurcations of the airways. In the case of inhaled medicines, and depending on the size of the particles in the formulation, airway bifurcations are areas of preferential deposition. Here, we use Direct Numerical Simulations (DNS) to examine aerosol deposition in the case of turbulent flow through a realistic representation of the tracheal bifurcation. We examine the flow characteristics in detail, including the turbulent structures and how they affect the deposition of particles of different sizes. DNS results are compared with RANS computations. Supported by the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 315760 HEXACOMM.

  11. Targeted Delivery Systems for Molecular Therapy in Skeletal Disorders

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

    In this paper, we provide an overview an extensive range of colloidal drug delivery systems with special focus on vesicular and particulates systems that are being used in research or might be potentially useful as carriers systems for drug or active biomolecules or as cell carriers with application in the therapeutic field. We present some important examples of commercially available drug delivery systems with applications in research or in clinical fields. This class of systems is widely used due to excellent drug targeting, sustained and controlled release behavior, higher entrapment efficiency of drug molecules, prevention of drug hydrolysis or enzymatic degradation, and improvement of therapeutic efficacy. These characteristics help in the selection of suitable carrier systems for drug, cell, and gene delivery in different fields. PMID:25955882

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. In vivo Evaluation of Self Emulsifying Drug Delivery System for Oral Delivery of Nevirapine

    PubMed Central

    Chudasama, A. S.; Patel, V. V.; Nivsarkar, M.; Vasu, Kamala K.; Shishoo, C. J.

    2014-01-01

    Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation. However, HIV/AIDS patients experience a variety of functional and anatomical abnormalities in gastrointestinal tract that result in diarrhoea and nutrient malabsorption. Medium chain triglycerides are readily absorbed from the small bowel under conditions in which the absorption of long chain triglycerides is impaired. Therefore, nevirapine self-emulsifying drug delivery system containing medium chain fatty acid, caprylic acid and a solubilizer, Soluphor® P (2-pyrrolidone) was developed and found to be superior to the marketed conventional suspension with respect to in vitro diffusion and ex vivo intestinal permeability. This self-emulsifying drug delivery system has now been further investigated for in vivo absorption in an animal model. The contribution of caprylic acid and Soluphor® P on in vivo absorption of nevirapine was also studied in the present study. The bioavailability of nevirapine from self-emulsifying drug delivery system, after oral administration, was 2.69 times higher than that of the marketed suspension. The improved bioavailability could be due to absorption of nevirapine via both portal and intestinal lymphatic routes. The study indicates that medium chain or structured triglycerides can be a better option to develop self-emulsifying drug delivery system for lipophilic and extensively metabolised drugs like nevirapine for patients with AIDS-associated malabsorption. PMID:25035533

  16. In vivo Evaluation of Self Emulsifying Drug Delivery System for Oral Delivery of Nevirapine.

    PubMed

    Chudasama, A S; Patel, V V; Nivsarkar, M; Vasu, Kamala K; Shishoo, C J

    2014-05-01

    Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation. However, HIV/AIDS patients experience a variety of functional and anatomical abnormalities in gastrointestinal tract that result in diarrhoea and nutrient malabsorption. Medium chain triglycerides are readily absorbed from the small bowel under conditions in which the absorption of long chain triglycerides is impaired. Therefore, nevirapine self-emulsifying drug delivery system containing medium chain fatty acid, caprylic acid and a solubilizer, Soluphor(®) P (2-pyrrolidone) was developed and found to be superior to the marketed conventional suspension with respect to in vitro diffusion and ex vivo intestinal permeability. This self-emulsifying drug delivery system has now been further investigated for in vivo absorption in an animal model. The contribution of caprylic acid and Soluphor(®) P on in vivo absorption of nevirapine was also studied in the present study. The bioavailability of nevirapine from self-emulsifying drug delivery system, after oral administration, was 2.69 times higher than that of the marketed suspension. The improved bioavailability could be due to absorption of nevirapine via both portal and intestinal lymphatic routes. The study indicates that medium chain or structured triglycerides can be a better option to develop self-emulsifying drug delivery system for lipophilic and extensively metabolised drugs like nevirapine for patients with AIDS-associated malabsorption. PMID:25035533

  17. Vaporization as a smokeless cannabis delivery system: a pilot study.

    PubMed

    Abrams, D I; Vizoso, H P; Shade, S B; Jay, C; Kelly, M E; Benowitz, N L

    2007-11-01

    Although cannabis may have potential therapeutic value, inhalation of a combustion product is an undesirable delivery system. The aim of the study was to investigate vaporization using the Volcano((R)) device as an alternative means of delivery of inhaled Cannabis sativa. Eighteen healthy inpatient subjects enrolled to compare the delivery of cannabinoids by vaporization to marijuana smoked in a standard cigarette. One strength (1.7, 3.4, or 6.8% tetrahydrocannabinol (THC)) and delivery system was randomly assigned for each of the 6 study days. Plasma concentrations of Delta-9-THC, expired carbon monoxide (CO), physiologic and neuropsychologic effects were the main outcome measures. Peak plasma concentrations and 6-h area under the plasma concentration-time curve of THC were similar. CO levels were reduced with vaporization. No adverse events occurred. Vaporization of cannabis is a safe and effective mode of delivery of THC. Further trials of clinical effectiveness of cannabis could utilize vaporization as a smokeless delivery system. PMID:17429350

  18. Training Delivery Systems for Adult Learners. A Bibliography.

    ERIC Educational Resources Information Center

    Florida State Univ., Tallahassee. Center for Instructional Development and Services.

    This bibliography focuses on the training needs of adults and the incorporation of the most effective training delivery systems for adults into job training programs. It includes citations exploring current training practices, methods, and philosophies in both the private sector and the educational system; how each system can learn from the…

  19. 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.

  20. Hydrocolloid-based nutraceutical delivery systems

    SciTech Connect

    Janaswamy, Srinivas; Youngren, Susanne R.

    2012-07-11

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

  1. Improving vaccine delivery using novel adjuvant systems.

    PubMed

    Pichichero, Michael E

    2008-01-01

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

  2. Coacervate delivery systems for proteins and small molecule drugs

    PubMed Central

    Johnson, Noah R; Wang, Yadong

    2015-01-01

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

  3. Data-driven aerosol development in the GEOS-5 modeling and data assimilation system

    NASA Astrophysics Data System (ADS)

    Darmenov, A.; da Silva, A.; Liu, X.; Colarco, P. R.

    2013-12-01

    Atmospheric aerosols are important radiatively active agents that also affect clouds, atmospheric chemistry, the water cycle, land and ocean biogeochemistry. Furthermore, exposure to anthropogenic and/or natural fine particulates can have negative health effects. No single instrument or model is capable of quantifying the diverse and dynamic nature of aerosols at the range of spatial and temporal scales at which they interact with the other constituents and components of the Earth system. However, applying model-data integration techniques can minimize limitations of individual data products and remedy model deficiencies. The Goddard Earth Observing System Model, Version 5 (GEOS-5) is the latest version of the NASA Global Modeling and Assimilation Office (GMAO) Earth system model. GEOS-5 is a modeling and data assimilation framework well suited for aerosol research. It is being used to perform aerosol re-analysis and near real-time aerosol forecast on a global scale at resolutions comparable to those of aerosol products from modern spaceborne instruments. The aerosol processes in GEOS-5 derive from the Goddard Chemistry Aerosol Radiation and Transport (GOCART) but it is implemented on-line, within the climate model. GEOS-5 aerosol modeling capabilities have recently been enhanced by inclusion of the Modal Aerosol Microphysics module (MAM-7) originally developed in the Community Earth System Model (CESM) model. This work will present examples of data driven model development that include refining parameterization of sea-salt emissions, tuning of biomass burning emissions from vegetation fires and the effect of the updated emissions on the modeled direct aerosol forcing. We will also present results from GOES-5/MAM-7 model evaluation against AOD and particulate pollution datasets, and outline future directions of aerosol data assimilation in the GEOS-5 system.

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

    PubMed

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

    2013-01-01

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

  5. Dendrimeric Systems and Their Applications in Ocular Drug Delivery

    PubMed Central

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

    2013-01-01

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

  6. Osmotically controlled drug delivery system with associated drugs.

    PubMed

    Gupta, Brahma Prakash; Thakur, Navneet; Jain, Nishi P; Banweer, Jitendra; Jain, Surendra

    2010-01-01

    Conventional drug delivery systems have slight control over their drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the controlled or modified release drug delivery systems. They include dosage forms for oral and transdermal administration as well as injectable and implantable systems. For most of drugs, oral route remains as the most acceptable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Development of an extended release dosage form also requires reasonable absorption throughout the gastro-intestinal tract (GIT). Among the available techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most appropriate one. Osmotic drug delivery systems release the drug with the zero order kinetics which does not depend on the initial concentration and the physiological factors of GIT. This review brings out new technologies, fabrication and recent clinical research in osmotic drug delivery. PMID:21486532

  7. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Niosomes: a controlled and novel drug delivery system.

    PubMed

    Rajera, Rampal; Nagpal, Kalpana; Singh, Shailendra Kumar; Mishra, Dina Nath

    2011-01-01

    During the past decade formulation of vesicles as a tool to improve drug delivery, has created a lot of interest amongst the scientist working in the area of drug delivery systems. Vesicular system such as liposomes, niosomes, transferosomes, pharmacosomes and ethosomes provide an alternative to improve the drug delivery. Niosomes play an important role owing to their nonionic properties, in such drug delivery system. Design and development of novel drug delivery system (NDDS) has two prerequisites. First, it should deliver the drug in accordance with a predetermined rate and second it should release therapeutically effective amount of drug at the site of action. Conventional dosage forms are unable to meet these requisites. Niosomes are essentially non-ionic surfactant based multilamellar or unilamellar vesicles in which an aqueous solution of solute is entirely enclosed by a membrane resulting from the organization of surfactant macromolecules as bilayer. Niosomes are formed on hydration of non-ionic surfactant film which eventually hydrates imbibing or encapsulating the hydrating aqueous solution. The main aim of development of niosomes is to control the release of drug in a sustained way, modification of distribution profile of drug and for targeting the drug to the specific body site. This paper deals with composition, characterization/evaluation, merits, demerits and applications of niosomes. PMID:21719996

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

    PubMed

    Tesfamariam, Belay

    2016-09-28

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

  12. Formulation and evaluation of ondansetron nasal delivery systems.

    PubMed

    Cho, Eunsook; Gwak, Hyesun; Chun, Inkoo

    2008-02-12

    This study aimed to formulate and evaluate nasal delivery systems containing ondansetron hydrochloride. In the in vitro study, the permeation rate with the addition of 10% polyethylene glycol 300 (PEG 300) to aqueous solution containing 0.01% benzalkonium chloride (BC) and 10% sulfobutylether beta-cyclodextrin sodium salt (SBCD) was somewhat more rapid up to 1.5h compared to the addition of 10% PG. The permeation flux increased as the drug concentration increased regardless of the vehicles used. The addition of nicotinamide or chitosan to aqueous drug solution (40 mg/ml) with 10% PEG 300 and 0.01% BC rather decreased permeation rate and delayed lag time. Even though cyclodextrins including SBCD or dimethyl-ss-cyclodextrin failed to show permeation enhancing effects of ondansetron hydrochloride, the addition of 10% SBCD to aqueous solution containing 10% PEG 300 and 0.01% BC could be a good candidate for ondansetron nasal delivery systems because of its safety profile, stable storage in refrigerator and solubilizing effect. With the above formulation, the nasal delivery system increased AUC0-2h and Cmax by 2.1 and 1.7 times compared to those of oral delivery, respectively while there was no difference found in AUC0-2h with intravenous administration. Therefore, the nasal delivery system of ondansetron hydrochloride formulated in this study was feasible for nasal administration. PMID:17822864

  13. New capabilities for space-based cloud and aerosols measurements: The Cloud-Aerosol Transport System (CATS)

    NASA Astrophysics Data System (ADS)

    Yorks, J. E.; McGill, M. J.; Hlavka, D. L.; Palm, S. P.; Hart, W. D.; Nowottnick, E. P.; Vaughan, M.; Rodier, S. D.; Colarco, P. R.; da Silva, A.; Buchard-Marchant, V.

    2013-12-01

    Current uncertainties in cloud and aerosol properties limit our ability to accurately model the Earth's climate system and predict climate change. These limitations are due primarily to difficulties in adequately measuring aerosols and clouds on a global scale. NASA's A-Train satellites provide an unprecedented opportunity to address these uncertainties. In particular, the Cloud-Aerosol Lidar Infrared Pathfinder Spaceborne Observations (CALIPSO) satellite provides vertical profiles of cloud and aerosol properties. The CALIOP lidar onboard CALIPSO has reached its seventh year of operation, well past its expected lifetime. The ATLID lidar on EarthCARE is not expected to launch until 2016 or later. If the CALIOP lidar fails before a new mission is operational, there will be a gap in global lidar measurements. The Cloud-Aerosol Transport System (CATS), built at NASA Goddard Space Flight Center as a payload for the International Space Station (ISS), is set to launch in the summer of 2014. CATS is an elastic backscatter lidar with three wavelengths (1064, 532, 355 nm) and HSRL capability at 532 nm. Depolarization measurements will be made at all three wavelengths. The ISS orbit is a 51 degree inclination orbit at an altitude of about 405 km. This orbit provides more comprehensive coverage of the tropics and mid-latitudes than sun-synchronous orbiting sensors, with nearly a three day repeat cycle. Thus, science applications of CATS include cloud and aerosol climate studies, air quality monitoring, and smoke/volcanic plume tracking. The primary science objectives of CATS include: continuing the CALIPSO aerosol and cloud vertical profile data record, providing near real time data to support operational applications such as air quality modeling, and advancing technology in support of future mission development using the HSRL channel. Furthermore, the vertical profiles of cloud and aerosol properties provided by CATS will complement current and future passive satellite

  14. Design of Educational Delivery Systems for Lifelong Learning.

    ERIC Educational Resources Information Center

    Gibson, R. Oliver; Gilbert, Randall L.

    To clarify delivery system concepts, several topics will be addressed: educational needs of lower-income older people, formulation of a design concept, specification of the system's concrete aspects, and research/development implications. As the proportion of persons over age sixty-four grows and sensitivity to unmet lifelong learning needs rises,…

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

    ERIC Educational Resources Information Center

    Swalec, John J.

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

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

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

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

  17. Importance of dual delivery systems for bone tissue engineering.

    PubMed

    Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

    2016-03-10

    Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. PMID:26805518

  18. Biologically erodable microspheres as potential oral drug delivery systems

    NASA Astrophysics Data System (ADS)

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

    1997-03-01

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

  19. A clinical perspective on mucoadhesive buccal drug delivery systems

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-07-01

    Esophageal cancer patients are often diagnosed as "advanced" cases. These patients are subjected to palliative stenting using self-expanding metallic stents (SEMS) to maintain oral alimentation. Unfortunately, SEMS get reoccluded due to tumor growth, in and over the stent struts. To investigate potential solutions to this problem, docetaxel (DTX) delivery films were prepared using PurSil AL 20 (PUS), which can be used as a covering material for the SEMS. Drug-polymer miscibility and interactions were studied. Bilayer films were prepared by adhering the blank film to the DTX loaded film in order to maintain the unidirectional delivery to the esophagus. In vitro release and the local DTX delivery were studied using in vitro permeation experiments. It was found that DTX and PUS were physically and chemically compatible. The bilayer films exhibited sustained release (>30 days) and minimal DTX permeation through esophageal tissues in vitro. The rate-determining step for the DTX delivery was calculated. It was found that >0.9 fraction of rate control lies with the esophageal tissues, suggesting that DTX delivery can be sustained for longer periods compared to the in vitro release observed. Thus, the bilayer films can be developed as a localized sustained delivery system in combination with the stent. PMID:25936529

  1. Gastric retentive drug-delivery systems.

    PubMed

    Hwang, S J; Park, H; Park, K

    1998-01-01

    The development of a long-term oral controlled-release dosage form has been difficult mainly because of the transit of the dosage form through the gastrointestinal (GI) tract. Several approaches to extend gastric residence time have been tried. The most commonly used systems are (1) intragastric floating systems, (2) high-density systems, (3) mucoadhesive systems, (4) magnetic systems, (5) unfoldable, extendible, or swellable systems, and (6) superporous hydrogel systems. The concept of each approach is examined, and improvements that are needed for further development are discussed. Background materials in the GI physiology that are necessary for understanding the concept and usefulness of each approach are also provided. PMID:9699081

  2. Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  4. Technical study of some major parameters influencing the performance of an aerosol delivery equipment suitable for calves.

    PubMed

    Genicot, B; Peckova, M; Close, R; Lindsey, J K; Lambert, P; Lekeux, P

    1994-01-01

    Aerosol delivery equipment, suitable for the treatment of bovine respiratory dysfunctions and including 2 parallelly positioned jet nebulizers, was studied in depth in order to determine the optimal working conditions in the field. Indeed, some factors might reasonably alter the performance of this equipment. Among these factors, the influences of the parallel position of jet nebulizers (in order to accommodate the breathing requirements of the cattle and achieve a rapid treatment), of the long feed pipe delivering compressed air (in order to keep the animal away from the compressor unit), and finally of the ambient temperature were studied, this equipment being essentially used during the winter season. This equipment could accommodate the breathing needs of cattle weighing up to 225 kg if a pressure of 600 kPa was developed upstream to the nebulizers. The rate of atomization was significantly reduced when working at ambient air temperatures (272.25 K < T < 274.65 K) close to those encountered in winter. This was especially true when pressure upstream to the nebulizers did not exceed 500 kPa. The immersion of the feed pipe for compressed air in hot water led to an increase in the rate of atomization without raising evaporative water losses, and reduced the drop in temperature in the nebulizer solution. Finally, the rate of atomization significantly increased when the face mask including the nebulizers was maintained so that the nebulizers were in a vertical position or at an angle not less than 60 degrees with respect to the ground. PMID:7951349

  5. Measurements of atmospheric aerosol vertical distributions above Svalbard, Norway, using unmanned aerial systems (UAS)

    NASA Astrophysics Data System (ADS)

    Bates, T. S.; Quinn, P. K.; Johnson, J. E.; Corless, A.; Brechtel, F. J.; Stalin, S. E.; Meinig, C.; Burkhart, J. F.

    2013-08-01

    Atmospheric aerosol vertical distributions were measured above Svalbard, Norway, in April 2011 during the Cooperative Investigation of Climate-Cryosphere Interactions campaign (CICCI). Measurements were made of the particle number concentration and the aerosol light absorption coefficient at three wavelengths. A filter sample was collected on each flight at the altitude of maximum particle number concentration. The filters were analyzed for major anions and cations. The aerosol payload was flown in a NOAA/PMEL MANTA Unmanned Aerial System (UAS). A total of 18 flights were flown during the campaign totaling 38 flight hours. The data show frequent aerosol layers aloft with high particle number concentration (1000 cm-3) and enhanced aerosol light absorption (1 Mm-1). Air mass histories of these aerosol layers were assessed using FLEXPART particle dispersion modeling. The data contribute to an assessment of sources of BC to the Arctic and potential climate impacts.

  6. Measurements of atmospheric aerosol vertical distributions above Svalbard, Norway using unmanned aerial systems (UAS)

    NASA Astrophysics Data System (ADS)

    Bates, T. S.; Quinn, P. K.; Johnson, J. E.; Corless, A.; Brechtel, F. J.; Stalin, S. E.; Meinig, C.; Burkhart, J. F.

    2013-03-01

    Atmospheric aerosol vertical distributions were measured above Svalbard, Norway in April 2011 during the Cooperative Investigation of Climate-Cryosphere Interactions campaign (CICCI). Measurements were made of the particle number concentration and the aerosol light absorption coefficient at three wavelengths. A filter sample was collected on each flight at the altitude of maximum particle number concentration. The filters were analyzed for major anions and cations. The aerosol payload was flown in a NOAA/PMEL MANTA Unmanned Aerial System (UAS). A total of 18 flights were flown during the campaign totaling 38 flight hours. The data show frequent aerosol layers aloft with high particle number concentration (1000 cm-3 and enhanced aerosol light absorption (1 Mm-1). Air mass histories of these aerosol layers were assessed using FLEXPART particle dispersion modeling. The data contribute to an assessment of sources of BC to the Arctic and potential climate impacts.

  7. Programmable nanomedicine: synergistic and sequential drug delivery systems

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  8. The Vacuum-Operated Nutrient Delivery System: hydroponics for microgravity.

    PubMed

    Brown, C S; Cox, W M; Dreschel, T W; Chetirkin, P V

    1992-11-01

    A nutrient delivery system that may have applicability for growing plants in microgravity is described. The Vacuum-Operated Nutrient Delivery System (VONDS) draws nutrient solution across roots that are under a partial vacuum at approximately 91 kPa. Bean (Phaseolus vulgaris L. cv. Blue Lake 274) plants grown on the VONDS had consistently greater leaf area and higher root, stem, leaf, and pod dry weights than plants grown under nonvacuum control conditions. This study demonstrates the potential applicability of the VONDS for growing plants in microgravity for space biology experimentation and/or crop production. PMID:11537607

  9. Cyclosporine Amicellar delivery system for dry eyes

    PubMed Central

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

    2016-01-01

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

  10. An image-based automatic mesh generation and numerical simulation for a population-based analysis of aerosol delivery in the human lungs

    NASA Astrophysics Data System (ADS)

    Miyawaki, Shinjiro; Tawhai, Merryn H.; Hoffman, Eric A.; Lin, Ching-Long

    2013-11-01

    The authors propose a method to automatically generate three-dimensional subject-specific airway geometries and meshes for computational fluid dynamics (CFD) studies of aerosol delivery in the human lungs. The proposed method automatically expands computed tomography (CT)-based airway skeleton to generate the centerline (CL)-based model, and then fits it to the CT-segmented geometry to generate the hybrid CL-CT-based model. To produce a turbulent laryngeal jet known to affect aerosol transport, we developed a physiologically-consistent laryngeal model that can be attached to the trachea of the above models. We used Gmsh to automatically generate the mesh for the above models. To assess the quality of the models, we compared the regional aerosol distributions in a human lung predicted by the hybrid model and the manually generated CT-based model. The aerosol distribution predicted by the hybrid model was consistent with the prediction by the CT-based model. We applied the hybrid model to 8 healthy and 16 severe asthmatic subjects, and average geometric error was 3.8% of the branch radius. The proposed method can be potentially applied to the branch-by-branch analyses of a large population of healthy and diseased lungs. NIH Grants R01-HL-094315 and S10-RR-022421, CT data provided by SARP, and computer time provided by XSEDE.

  11. Vaccinia virus as a vaccine delivery system for marsupial wildlife.

    PubMed

    Cross, Martin L; Fleming, Stephen B; Cowan, Phil E; Scobie, Susie; Whelan, Ellena; Prada, Diana; Mercer, Andrew A; Duckworth, Janine A

    2011-06-20

    Vaccines based on recombinant poxviruses have proved successful in controlling diseases such as rabies and plague in wild eutherian mammals. They have also been trialled experimentally as delivery agents for fertility-control vaccines in rodents and foxes. In some countries, marsupial mammals represent a wildlife disease reservoir or a threat to conservation values but, as yet there has been no bespoke study of efficacy or immunogenicity of a poxvirus-based vaccine delivery system in a marsupial. Here, we report a study of the potential for vaccination using vaccinia virus in the Australian brushtail possum Trichosurus vulpecula, an introduced pest species in New Zealand. Parent-strain vaccinia virus (Lister) infected 8/8 possums following delivery of virus to the oral cavity and outer nares surfaces (oronasal immunisation), and persisted in the mucosal epithelium around the palatine tonsils for up to 2 weeks post-exposure. A recombinant vaccinia virus construct (VV399, which expresses the Eg95 antigen of the hydatid disease parasite Echinococcus granulosus) was shown to infect 10/15 possums after a single-dose oronasal delivery and to also persist. Both parent vaccinia virus and the VV399 construct virus induced peripheral blood lymphocyte reactivity against viral antigens in possums, first apparent at 4 weeks post-exposure and still detectable at 4 months post-exposure. Serum antibody reactivity to Eg95 was recorded in 7/8 possums which received a single dose of the VV399 construct and 7/7 animals which received triple-dose delivery, with titre end-points in the latter case exceeding 1/4000 dilution. This study demonstrates that vaccinia virus will readily infect possums via a delivery means used to deploy wildlife vaccines, and in doing is capable of generating immune reactivity against viral and heterologous antigens. This highlights the future potential of recombinant vaccinia virus as a vaccine delivery system in marsupial wildlife. PMID:21570435

  12. Micro and nanoparticle drug delivery systems for preventing allotransplant rejection.

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2015-04-01

    Describing, evaluating, and conducting research on the questions raised by comparative effectiveness research and characterizing care delivery organizations of all kinds, from independent individual provider units to large integrated health systems, has become imperative. Recognizing this challenge, the Delivery Systems Committee, a subgroup of the Agency for Healthcare Research and Quality's Effective Health Care Stakeholders Group, which represents a wide diversity of perspectives on health care, created a draft framework with domains and elements that may be useful in characterizing various sizes and types of care delivery organizations and may contribute to key outcomes of interest. The framework may serve as the door to further studies in areas in which clear definitions and descriptions are lacking. PMID:24922130

  15. Gene Expression and Pulmonary Toxicity of Chitosan-graft- Polyethylenimine as Aerosol Gene Carrier.

    PubMed

    Kwon, Jung-Taek; Jiang, Hu-Lin; Minai-Tehrani, Arash; Gyu Woo, Chang; Choi, Mansoo; Cho, Chong-Su; Kim, Yeon-Soo; Cho, Myung-Haing

    2013-01-01

    Chitosan-graft-polyethylenimine (CHI-g-PEI) copolymer has been used for the improvement of low transfection efficiency of chitosan. The present study aims to test the pulmonary toxicity and efficiency of CHI-g-PEI as an aerosol gene carrier. Mice were exposed to aerosol containing green-fluorescent protein (GFP)-polyethylenimine (PEI) or GFP-CHI-g-PEI complexes for 30 min during the development of our nose-only exposure chamber (NOEC) system. CHI-g-PEI-mediated aerosol delivery demonstrated 15.65% enhancement of the fluorescence intensity. Compared to PEI, CHI-g-PEI showed no significant pulmonary toxicity. In summary, using CHI-g-PEI is safe and shows high transfection in aerosol gene delivery to animals, and enhanced efficiency was achieved through our aerosol gene delivery system. Therefore, CHI-g-PEI and this system would be applicable to future study for aerosol gene therapy. PMID:24250601

  16. Assessment of Alternative Student and Delivery Systems: Assessment of the Current Delivery System. Supplement I to the Final Report.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    The effects of the current student financial aid delivery system on five major participant groups are examined: federal government, states/guarantee agencies, postsecondary institutions, lenders and secondary markets, and applicants and families. Attention is directed to effects of the current system, including: administrative costs, fund…

  17. Aerosol deposition in the human respiratory system. Final report

    SciTech Connect

    Yu, C.P.

    1988-01-01

    Attempts were made to develop mathematical models for the deposition of aerosols in the human respiratory system. Expressions were obtained for the mean deposition efficiency for nasal inspiration, nasal expiration, and mouth inspiration. A determination was made of statistical properties associated with each deposition efficiency due to intersubject and intrasubject variabilities. Expressions were then derived for head deposition with combined nose and mouth breathing. In the lung, deposition is a result primarily of impaction, sedimentation, and diffusion. While there was no adequate model for impaction, several deposition formulae for sedimentation were derived as well as ones for diffusion. Studies were also made of the particle charge effect, as the electrostatic image force on a particle contributes to its deposition. There is, however, a threshold charge per particle below which the particle charge has no effect on deposition. Deposition data on ultrafine particles is scarce due to the difficulties in conducting proper experiments.

  18. Effects of aerosols on clear-sky solar radiation in the ALADIN-HIRLAM NWP system

    NASA Astrophysics Data System (ADS)

    Gleeson, Emily; Toll, Velle; Pagh Nielsen, Kristian; Rontu, Laura; Masek, Jan

    2016-05-01

    The direct shortwave radiative effect of aerosols under clear-sky conditions in the Aire Limitee Adaptation dynamique Developpement InterNational - High Resolution Limited Area Model (ALADIN-HIRLAM) numerical weather prediction system was investigated using three shortwave radiation schemes in diagnostic single-column experiments: the Integrated Forecast System (IFS), acraneb2 and the hlradia radiation schemes. The multi-band IFS scheme was formerly used operationally by the European Centre for Medium Range Weather Forecasts (ECMWF) whereas hlradia and acraneb2 are broadband schemes. The former is a new version of the HIRLAM radiation scheme while acraneb2 is the radiation scheme in the ALARO-1 physics package. The aim was to evaluate the strengths and weaknesses of the numerical weather prediction (NWP) system regarding aerosols and to prepare it for use of real-time aerosol information. The experiments were run with particular focus on the August 2010 Russian wildfire case. Each of the three radiation schemes accurately (within ±4 % at midday) simulates the direct shortwave aerosol effect when observed aerosol optical properties are used. When the aerosols were excluded from the simulations, errors of more than +15 % in global shortwave irradiance were found at midday, with the error reduced to +10 % when standard climatological aerosols were used. An error of -11 % was seen at midday if only observed aerosol optical depths at 550 nm, and not observation-based spectral dependence of aerosol optical depth, single scattering albedos and asymmetry factors, were included in the simulations. This demonstrates the importance of using the correct aerosol optical properties. The dependency of the direct radiative effect of aerosols on relative humidity was tested and shown to be within ±6 % in this case. By modifying the assumptions about the shape of the IFS climatological vertical aerosol profile, the inherent uncertainties associated with assuming fixed vertical

  19. Industrial beam delivery system for ultra-short pulsed laser

    NASA Astrophysics Data System (ADS)

    Funck, Max C.; Wedel, Björn; Kayander, Ilya; Niemeyer, Jörg

    2015-03-01

    Beam delivery systems are an integral part of industrial laser equipment. Separating laser source and application fiber optic beam delivery is employed wherever great flexibility is required. And today, fiber optic beam delivery of several kW average power is available for continuous wave operation using multimode step index fibers with core diameters of several 100 μm. However, during short-pulse or even ultra-short pulse laser operation step index fibers fail due to high power density levels and nonlinear effects such as self-focusing and induced scattering. Hollow core photonic crystal fibers (HC-PCF) are an alternative to traditional fibers featuring light propagation mostly inside a hollow core, enabling high power handling and drastically reduced nonlinear effects. These fibers have become available during the past decade and are used in research but also for fiber laser systems and exhibit a growing popularity. We report on using HC-PCF fibers and their integration into an industrial beam delivery package comparable to today's fiber optic standards and will discuss power handling, beam quality and efficiency as well as future prospects of this technology. In a preliminary industrial beam delivery setup 300 fs pulses at 100 W average power could be delivered.

  20. Photoacoustic sensor system for the quantification of soot aerosols (abstract)

    NASA Astrophysics Data System (ADS)

    Haisch, C.; Beck, H.; Niessner, R.

    2003-01-01

    The influence of soot particles on human health as well as global and local climate is well established by now. Hence, the need for fast and sensitive soot detection in urban and remote areas is obvious. The state of the art thermochemical detection methods for soot analysis is based on filter sampling and subsequent wet chemical analysis and combustion, which requires laborious and time consuming sample preparation. Due to the integration on a filter, a time-resolved analysis is not possible. The presented photoacoustic sensor system is optimized for a highly sensitive and fast on-line and in situ quantification of soot. Soot particles, as classical "black absorbers," absorb electromagnetic radiation over the whole spectrum. Two similar systems are introduced. The first system is designed for the development and testing of combustion engines, mainly the next generation of diesel engines. In the next decade, legal thresholds for extremely low particle emissions are foreseen. Their implementation will be only possible if a time-resolved soot detection with sufficient sensitivity can be realized as the highest particle emissions from diesel engines are generated only for seconds during load changes. During a load change, the emitted soot concentrations can rise several orders of magnitude for only a period of few seconds. The system combines a time resolution of 1 s (sampling rate 1 Hz) with an aerosol mass sensitivity better than 10 μg m-3. Up to a maximum dimension of about 800 nm the signal is independent of the particle size. The systems consist of two photoacoustic cells, which are operated in a differential mode to avoid cross sensitivities. The cells are built as acoustical resonators to increase sensitivity. A diode laser with a wavelength of 810 nm and an output power of 1.1 W is employed for excitation. Its collimated beam passes first through the reference cell and then through the measurement cell. To avoid condensation of water, the cells are heated to

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  2. Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery.

    PubMed

    Bandeira, Elga; Lopes-Pacheco, Miquéias; Chiaramoni, Nadia; Ferreira, Débora; Fernandez-Ruocco, Maria J; Prieto, Maria J; Maron-Gutierrez, Tatiana; Perrotta, Ramiro M; de Castro-Faria-Neto, Hugo C; Rocco, Patricia R M; Alonso, Silvia Del Valle; Morales, Marcelo M

    2016-01-01

    Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l-tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases. PMID:27199766

  3. Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery

    PubMed Central

    Bandeira, Elga; Lopes-Pacheco, Miquéias; Chiaramoni, Nadia; Ferreira, Débora; Fernandez-Ruocco, Maria J.; Prieto, Maria J.; Maron-Gutierrez, Tatiana; Perrotta, Ramiro M.; de Castro-Faria-Neto, Hugo C.; Rocco, Patricia R. M.; Alonso, Silvia del Valle; Morales, Marcelo M.

    2016-01-01

    Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l-tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases. PMID:27199766

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-07-01

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

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

    PubMed

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

    2015-01-01

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

  7. Aerosol delivery of trail pheromone disrupts red imported fire ant, Solenopsis invicta, foraging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Toxic bait systems are widely used for control of the fire ant, Solenopsis invicta, one of the most aggressive and invasive species in the world. We prepared the trail pheromone Z,E-a-farnesene (91% purity) from isomerised apple extracts and tested disruption of worker trail orientation using an aer...

  8. New Measurements of Aerosol Vertical Structure from Space using the NASA Geoscience Laser Altimeter System (GLAS): Applications for Aerosol Transport Models

    NASA Technical Reports Server (NTRS)

    Welton, E. J.; Spinhime, J.; Palm, S.; Hlavka, D.; Hart, W.; Ginoux, P.; Chin, M.; Colarco, P.

    2004-01-01

    In the past, satellite measurements of aerosols have only been possible using passive sensors. Analysis of passive satellite data has lead to an improved understanding of aerosol properties, spatial distribution, and their effect on the earth,s climate. However, direct measurement of aerosol vertical distribution has not been possible using only the passive data. Knowledge of aerosol vertical distribution is important to correctly assess the impact of aerosol absorption, for certain atmospheric correction procedures, and to help constrain height profiles in aerosol transport models. On January 12,2003 NASA launched the first satellite-based lidar, the Geoscience Laser Altimeter System (GLAS), onboard the ICESat spacecraft. GLAS is both an altimeter and an atmospheric lidar, and obtains direct measurements of aerosol and cloud heights. Here we show an overview of GLAS, provide an update of its current status, and discuss how GLAS data will be useful for modeling efforts. In particular, a strategy of using GLAS to characterize the height profile of dust plumes over source regions will be presented, along with initial results. Such information can be used to validate and improve output from aerosol transport models. Aerosol height profile comparisons between GLAS and transport models will be shown for regions downwind of aerosol sources. We will also discuss the feasibility of assimilating GLAS profiles into the models in order to improve their output.

  9. New Measurements of Aerosol Vertical Structure from Space Using the NASA Geoscience Laser Altimeter System (GLAS): Applications for Aerosol Transport Models

    NASA Technical Reports Server (NTRS)

    Welton, Ellsworth J.; Ginoux, Paul; Colarco, Peter; Chin, Mian; Spinhirne, James D.; Palm, Steven P.; Hlavka, Dennis; Hart, William

    2003-01-01

    In the past, satellite measurements of aerosols have only been possible using passive sensors. Analysis of passive satellite data has lead to an improved understanding of aerosol properties, spatial distribution, and their effect on the earth s climate. However, direct measurement of aerosol vertical distribution has not been possible using only the passive data. Knowledge of aerosol vertical distribution is important to correctly assess the impact of aerosol absorption, for certain atmospheric correction procedures, and to help constrain height profiles in aerosol transport models. On January 12,2003 NASA launched the first satellite-based lidar, the Geoscience Laser Altimeter System (GLAS), onboard the ICESat spacecraft. GLAS is both an altimeter and an atmospheric lidar, and obtains direct measurements of aerosol and cloud heights. Here we show an overview of GLAS, provide an update of its current status, and discuss how GUS data will be useful for modeling efforts. In particular, a strategy of using GLAS to characterize the height profile of dust plumes over source regions will be presented, along with initial results. Such information can be used to validate and improve output from aerosol transport models. Aerosol height profile comparisons between GLAS and transport models will be shown for regions downwind of aerosol sources. We will also discuss the feasibility of assimilating GLAS profiles into the models in order to improve their output,

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

    PubMed

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

    2015-01-01

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

  11. Promoting quality of program delivery via an internet message delivery system.

    PubMed

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

    2013-01-01

    This article presents results from a study that evaluated an online message system designed to improve the delivery of prevention programs. We conducted a quasi-experimental study with 32 agencies and schools that implemented substance use prevention programs and examined differences between the comparison and intervention groups. We also examined the impact of dosage of the message system by comparing results among three groups of teachers: non-users, low users, and high users. Results for norm setting were marginally significant, such that teachers within the agencies assigned to the intervention condition scored higher on their understanding of norm setting at posttest compared to teachers within comparison agencies, after controlling for pretest knowledge scores and demographic items. In the model examining impact of dosage, high users of the intervention scored significantly higher on self-reported understanding of their program, quality of delivery, and program effectiveness compared to non-users. Low users of the intervention reported significantly higher quality of delivery compared to non-users. PMID:25445506

  12. A View of Earth's Aerosol System from Space to Your Office Chair

    NASA Technical Reports Server (NTRS)

    Colarco, Peter

    2008-01-01

    Aerosols are tiny particles and droplets suspended in the air. Each day you breathe in about 10 billion of them, about a half a million per breath. They are formed in nature by volcanoes, dust storms, sea spray, and emissions from vegetation. Humans create aerosols and alter their natural sources by burning fossil fuels and modifying land cover. Fires are another important source of aerosols; some are natural, such as wildfires started by lightning strikes, while others are from human-caused burning of vegetation for cooking, heating, and land clearing. Aerosols have complex effects on Earth's climate. In general, they cool the surface by reflecting (scattering) radiation from the sun back into space. Dust and smoke absorb solar radiation and heat the atmosphere where they are concentrated. Aerosols change the properties of clouds. Indeed, it would be very difficult to form clouds in the atmosphere without aerosols to act as 'seeds' for water to condense on. In aerosol polluted environments clouds tend to have smaller droplets than clouds formed in cleaner environments; these polluted clouds appear brighter from space because they reflect more sunlight, and they may persist longer and not rain as intensely. Aerosols also affect local air quality and visibility. Data collected by NASA satellites over the past decade have provided an unprecedented view of Earth's aerosol distribution and dramatically increased our understanding of where aerosols come from and just how far they travel in the atmosphere. In this talk I will discuss observations of aerosols from space and how they inform numerical transport models attempting to simulate the global aerosol system.

  13. Distinct Impacts of Aerosols on an Evolving Continental Cloud System during the RACORO Field Campaign

    NASA Astrophysics Data System (ADS)

    Lin, Y.; Wang, Y.; Zhang, R.; Liu, Y.

    2015-12-01

    Aerosol-cloud interactions have been investigated extensively but still remain high uncertainty due to the complexity of cloud microphysical processes under various dynamic and thermodynamic environments. Cloud-resolving Weather Research and Forecast (CR-WRF) model implemented with a two-moment bulk microphysics and a modified Goddard radiation scheme is employed to investigate aerosol effects on different cloud regimes and their transitions associated with a continental cloud system occurring from 25 May to 27 May, 2009 during the Department of Energy Atmospheric Radiation Measurement Routine AAF Clouds with Low Optical Water Depths Optical Radiative Observations (RACORO) field campaign. The simulated cloud properties and precipitation for the three different cloud regimes, including shallow cumuli, a deep convective cloud (DCC), and a stratus exhibit overall agreements with airborne and ground-based observations. Sensitivity studies with different aerosol scenarios reveal that the responses of cloud micro- and macrophysics to aerosol loading depend on the cloud regimes with monotonic or non-monotonic trend. Aerosol radiative effects modify the atmospheric thermodynamic condition and change the atmospheric stability, which induce different response from aerosol indirect effects. Our results also indicate that the overall aerosol effects on a cloud complex are distinct from those of the individual cloud types. The aerosol-cloud interaction for the different cloud regimes should be evaluated to assess the aerosol direct and indirect radiative forcings on regional and global climate.

  14. Analysis of DIAL/HSRL aerosol backscatter and extinction profiles during the SEAC4RS campaign with an aerosol assimilation system

    NASA Astrophysics Data System (ADS)

    Weaver, C. J.; da Silva, A. M., Jr.; Colarco, P. R.; Randles, C. A.

    2015-12-01

    We retrieve aerosol concentrations and optical information from vertical profiles of airborne 532 nm extinction and 532 and 1064 nm backscatter measurements made during the SEAC4RS summer 2013 campaign. The observations are from the High Spectral Resolution Lidar (HSRL) Airborne Differential Absorption Lidar (DIAL) on board the NASA DC-8. Instead of retrieving information about aerosol microphysical properties such as indexes of refraction, we seek information more directly applicable to an aerosol transport model - in our case the Goddard Chemistry Aerosol Radiation and Transport (GOCART) module used in the GEOS-5 Earth modeling system. A joint atmosphere/aerosol mini-reanalysis was performed for the SEAC4RS period using GEOS-5. The meteorological reanalysis followed the MERRA-2 atmospheric reanalysis protocol, and aerosol information from MODIS, MISR, and AERONET provided a constraint on the simulated aerosol optical depth (i.e., total column loading of aerosols). We focus on the simulated concentrations of 10 relevant aerosol species simulated by the GOCART module: dust, sulfate, and organic and black carbon. Our first retrieval algorithm starts with the SEAC4RS mini-reanalysis and adjusts the concentration of each GOCART aerosol species so that differences between the observed and simulated backscatter and extinction measurements are minimized. In this case, too often we are unable to simulate the observations by simple adjustment of the aerosol concentrations. A second retrieval approach adjusts both the aerosol concentrations and the optical parameters (i.e., assigned mass extinction efficiency) associated with each GOCART species. We present results from DC-8 flights over smoke from forest fires over the western US using both retrieval approaches. Finally, we compare our retrieved quantities with in-situ observations of aerosol absorption, scattering, and mass concentrations at flight altitude.

  15. Mercury sorbent delivery system for flue gas

    DOEpatents

    Klunder; ,Edgar B.

    2009-02-24

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

  16. NANOPARTICLE DELIVERY SYSTEMS IN CANCER VACCINES

    PubMed Central

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

    2013-01-01

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

  17. Strategies for Instructors Using Electronic Instruction Delivery Systems.

    ERIC Educational Resources Information Center

    Hutchinson, Michelle

    2000-01-01

    Presents strategies needed by instructors changing to electronic instruction delivery systems in higher education. Topics include developing pedagogical goals, including interactive learning; organization and hierarchy of course content; communications skills; making students feel welcome; fostering student-to-student collaboration; providing…

  18. Coordination polymer particles as potential drug delivery systems.

    PubMed

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

    2010-07-14

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

  19. Are E-Readers Viable Instructional Delivery Systems?

    ERIC Educational Resources Information Center

    Schcolnik, Miriam

    2002-01-01

    Reports on a study of e-readers, or electronic book readers, that investigated strategies adult users applied to reading in the new medium, kinds of texts users read, and text characteristics for e-reading. Discusses the process of reading, purposes of reading, and whether e-readers are viable instructional delivery systems. (Contains 63…

  20. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... property, making false claims, and obstruction of justice. The State agency may add other types of... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2010-01-01 2010-01-01 false Food delivery systems. 246.12 Section...

  1. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... property, making false claims, and obstruction of justice. The State agency may add other types of... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2011-01-01 2011-01-01 false Food delivery systems. 246.12 Section...

  2. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., receiving stolen property, making false claims, and obstruction of justice. The State agency may add other... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2012-01-01 2012-01-01 false Food delivery systems. 246.12 Section...

  3. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., receiving stolen property, making false claims, and obstruction of justice. The State agency may add other... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2013-01-01 2013-01-01 false Food delivery systems. 246.12 Section...

  4. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., receiving stolen property, making false claims, and obstruction of justice. The State agency may add other... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2014-01-01 2014-01-01 false Food delivery systems. 246.12 Section...

  5. Second-generation legal issues in integrated delivery systems.

    PubMed

    Teske, J M

    1995-01-01

    The formation and operation of integrated healthcare delivery systems raise significant legal issues. Some of these issues, such as antitrust, tax-exempt status, and fraud and abuse, have been discussed extensively. However, other legal issues, such as those involving management of business risk, use of systemwide information management, and securing of tax-exempt financing, have not received much attention. PMID:10146127

  6. Vocational Education Distance Learning Delivery System. Final Report.

    ERIC Educational Resources Information Center

    Hardy, Darcy Walsh

    A project was conducted to identify criteria and procedures for using a distance learning delivery system at the University of Texas TeleLearning Center to teach Health Occupations II to high school seniors. Another objective was expanding the current distance learning program for health occupations to include between 15 and 20 school districts.…

  7. 42 CFR 457.490 - Delivery and utilization control systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... State that elects to obtain health benefits coverage through a separate child health program must include in its State plan a description of the child health assistance provided under the plan for... control systems. A State must— (a) Describe the methods of delivery of child health assistance...

  8. NimbleTools: A Universally Designed Test Delivery System

    ERIC Educational Resources Information Center

    Russell, Michael; Hoffmann, Thomas; Higgins, Jennifer

    2009-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Drug delivery systems and combination therapy by using vinca alkaloids.

    PubMed

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

    2015-01-01

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

  11. The new organization of the health care delivery system.

    PubMed

    Shortell, S M; Hull, K E

    1996-01-01

    The U.S. health care system is restructuring at a dizzying pace. In many parts of the country, managed care has moved into third-generation models emphasizing capitated payment for enrolled lives and, in the process, turning most providers and institutions into cost centers to be managed rather than generators of revenue. While the full impact of the new managed care models remains to be seen, most evidence to date suggests that it tends to reduce inpatient use, may be associated with greater use of physician services and preventive care, and appears to result in no net differences either positive or negative with regard to quality or outcomes of care in comparison with fee-for-service plans. Some patients, however, tend to be somewhat less satisfied with scheduling of appointments and the amount of time spent with providers. There is no persuasive evidence that managed care lowers the rate of growth in overall health care costs within a given market. Further, managed care performance varies considerably across the country, and the factors influencing managed care performance are not well understood. Organized delivery systems are a somewhat more recent phenomenon representing various forms of ownership and strategic alliances among hospitals, physicians, and insurers designed to provide more cost-effective care to defined populations by achieving desired levels of functional, physician-system, and clinical integration. Early evidence suggests that organized delivery systems that are more integrated have the potential to provide more accessible coordinated care across the continuum, and appear to be associated with higher levels of inpatient productivity, greater total system revenue, greater total system cash flow, and greater total system operating margin than less integrated delivery forms. Some key success factors for developing organized delivery systems have been identified. Important roles are played by organizational culture, information systems, internal

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

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

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

  13. Medicated chewing gum, a novel drug delivery system

    PubMed Central

    Aslani, Abolfazl; Rostami, Farnaz

    2015-01-01

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

  14. 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. PMID:26027573

  15. Unsteady jet in designing innovative drug delivery system

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  16. RaPToRS Sample Delivery System

    NASA Astrophysics Data System (ADS)

    Henchen, Robert; Shibata, Kye; Krieger, Michael; Pogozelski, Edward; Padalino, Stephen; Glebov, Vladimir; Sangster, Craig

    2010-11-01

    At various labs (NIF, LLE, NRL), activated material samples are used to measure reaction properties. The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system quickly and safely moves these radioactive samples through a closed PVC tube via airflow. The carrier travels from the reaction chamber to the control and analysis station, pneumatically braking at the outlet. A reversible multiplexer routes samples from various locations near the shot chamber to the analysis station. Also, the multiplexer allows users to remotely load unactivated samples without manually approaching the reaction chamber. All elements of the system (pneumatic drivers, flow control valves, optical position sensors, multiplexers, Geiger counters, and release gates at the analysis station) can be controlled manually or automatically using a custom LabVIEW interface. A prototype is currently operating at NRL in Washington DC. Prospective facilities for Raptors systems include LLE and NIF.

  17. The Cloud-Aerosol Transport System (CATS): a New Lidar for Aerosol and Cloud Profiling from the International Space Station

    NASA Technical Reports Server (NTRS)

    Welton, Ellsworth J.; McGill, Matthew J.; Yorks, John E.; Hlavka, Dennis L.; Hart, William D.; Palm, Stephen P.; Colarco, Peter R.

    2011-01-01

    Spaceborne lidar profiling of aerosol and cloud layers has been successfully implemented during a number of prior missions, including LITE, ICESat, and CALIPSO. Each successive mission has added increased capability and further expanded the role of these unique measurements in wide variety of applications ranging from climate, to air quality, to special event monitoring (ie, volcanic plumes). Many researchers have come to rely on the availability of profile data from CALIPSO, especially data coincident with measurements from other A-Train sensors. The CALIOP lidar on CALIPSO continues to operate well as it enters its fifth year of operations. However, active instruments have more limited lifetimes than their passive counterparts, and we are faced with a potential gap in lidar profiling from space if the CALIOP lidar fails before a new mission is operational. The ATLID lidar on EarthCARE is not expected to launch until 2015 or later, and the lidar component of NASA's proposed Aerosols, Clouds, and Ecosystems (ACE) mission would not be until after 2020. Here we present a new aerosol and cloud lidar that was recently selected to provide profiling data from the International Space Station (ISS) starting in 2013. The Cloud-Aerosol Transport System (CATS) is a three wavelength (1064, 532, 355 nm) elastic backscatter lidar with HSRL capability at 532 nm. Depolarization measurements will be made at all wavelengths. The primary objective of CATS is to continue the CALIPSO aerosol and cloud profile data record, ideally with overlap between both missions and EarthCARE. In addition, the near real time data capability of the ISS will enable CATS to support operational applications such as air quality and special event monitoring. The HSRL channel will provide a demonstration of technology and a data testbed for direct extinction retrievals in support of ACE mission development. An overview of the instrument and mission will be provided, along with a summary of the science

  18. Determination of organic compounds from wood combustion aerosol nanoparticles by different gas chromatographic systems and by aerosol mass spectrometry.

    PubMed

    Laitinen, Totti; Martín, Sara Herrero; Parshintsev, Jevgeni; Hyötyläinen, Tuulia; Hartonen, Kari; Riekkola, Marja-Liisa; Kulmala, Markku; Pavón, José Luis Pérez

    2010-01-01

    Organic compounds in atmospheric nanoparticles have an effect on human health and the climate. The determination of these particles is challenged by the difficulty of sampling, the complexity of sample composition, and the trace-level concentrations of the compounds. Meeting the challenge requires the development of sophisticated sampling systems for size-resolved particles and the optimization of sensitive, accurate and simple analytical techniques and methods. A new sampling system is proposed where particles are charged with a bipolar charger and size-segregated with a differential mobility analyzer. This system was successfully used to sample particles from wood pyrolysis with particle sizes 30-100nm. Particles were analyzed by four techniques: comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry, gas chromatography-time-of-flight mass spectrometry, gas chromatography-quadrupole mass spectrometry, and aerosol mass spectrometry (aerosol MS). In the chromatographic techniques, particles were collected on a filter and analyzed off-line after sample preparation, whereas in the aerosol MS, particle analysis was performed directly from the particle source. Target compounds of the samples were polyaromatic hydrocarbons and n-alkanes. The analytical techniques were compared and their advantages and disadvantages were evaluated. The sampling system operated well and target compounds were identified in low concentrations. PMID:19945113

  19. Delivery Systems for Distance Education. ERIC Digest.

    ERIC Educational Resources Information Center

    Schamber, Linda

    This ERIC digest provides a brief overview of the video, audio, and computer technologies that are currently used to deliver instruction for distance education programs. The video systems described include videoconferencing, low-power television (LPTV), closed-circuit television (CCTV), instructional fixed television service (ITFS), and cable…

  20. Electronic Document Delivery: OCLC's Prototype System.

    ERIC Educational Resources Information Center

    Hickey, Thomas B.; Calabrese, Andrew M.

    1986-01-01

    Describes development of system for retrieval of documents from magnetic storage that uses stored font definition codes to control an inexpensive laser printer in the production of copies that closely resemble original document. Trends in information equipment and printing industries that will govern future application of this technology are…

  1. RESIDENCE-TO-GARDEN GREYWATER DELIVERY SYSTEM

    EPA Science Inventory

    Results will include a prototype of the system and garden, a summary of water and soil quality, and survey results. The website and educational materials will describe the project and water-consumption awareness. In addition, this project will deepen the university’s relation...

  2. Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications.

    PubMed

    Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary

    2016-01-01

    This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects. PMID:26938856

  3. Enhancing intestinal drug solubilisation using lipid-based delivery systems.

    PubMed

    Porter, Christopher J H; Pouton, Colin W; Cuine, Jean F; Charman, William N

    2008-03-17

    Lipid-based delivery systems are finding increasing application in the oral delivery of poorly water-soluble, lipophilic drugs. Whilst lipidic dose forms may improve oral bioavailability via several mechanisms, enhancement of gastrointestinal solubilisation remains argueably the most important method of absorption enhancement. This review firstly describes the mechanistic rationale which underpins the use of lipid-based delivery systems to enhance drug solubilisation and briefly reviews the available literature describing increases in oral bioavailability after the administration of lipid solution, suspension and self-emulsifying formulations. The use of in vitro methods including dispersion tests and more complex models of in vitro lipolysis as indicators of potential in vivo performance are subsequently described, with particular focus on recent data which suggests that the digestion of surfactants present in lipid-based formulations may impact on formulation performance. Finally, a series of seven guiding principles for formulation design of lipid-based delivery systems are suggested based on an analysis of recent data generated in our laboratories and elsewhere. PMID:18155801

  4. Self emulsifying drug delivery system (SEDDS) for phytoconstituents: a review.

    PubMed

    Chouhan, Neeraj; Mittal, Vineet; Kaushik, Deepak; Khatkar, Anurag; Raina, Mitali

    2015-01-01

    The self emulsifying drug delivery system (SEDDS) is considered to be the novel technique for the delivery of lipophillic plant actives. The self emulsifying (SE) formulation significantly enhance the solubility and bioavailability of poorly aqueous soluble phytoconstituents. The self emulsifying drug delivery system (SEDDS) can be developed for such plant actives to enhance the oral bioavailability using different excipients (lipid, surfactant, co solvent etc.) and their concentration is selected on the basis of pre formulation studies like phase equilibrium studies, solvent capacity of oil for drug and mutual miscibility of excipients. The present review focuses mainly on the development of SEDDS and effect of excipients on oral bioavailability and aqueous solubility of poorly water soluble phytoconstituents/ derived products. A recent list of patents issued for self emulsifying herbal formulation has also been included. The research data for various self emulsifying herbal formulation and patents issued were reviewed using different databases such as PubMed, Google Scholar, Google patents, Scopus and Web of Science. In a nutshell, we can say that SEDDS was established as a novel drug delivery system for herbals and with the advances in this technique, lots of patents on herbal SEDDS can be translated into the commercial products. PMID:25335929

  5. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    PubMed Central

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

    2014-01-01

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

  6. Self-Emulsifying Drug Delivery System for Enhancing Bioavailability and Lymphatic Delivery of Tacrolimus.

    PubMed

    Cho, Hea-Young; Choi, Ji-Hoon; Oh, In-Joon; Lee, Yong-Bok

    2015-02-01

    A self-emulsifying drug delivery system (SEDDS) containing tacrolimus has been developed to enhance the bioavailability and lymphatic delivery of tacrolimus. Solubility tests, combination tests, and phase diagrams were constructed for different sorts and ratios of oils, surfactants, and cosurfactants to identify optimal formulation. Optimized SEDDS was assessed for droplet size, zeta potential, stability in various media, and in vitro release. The tacrolimus-loaded SEDDS and commercial capsule (Prograf®) were orally administered (5 mg/kg) to rats. Whole blood, and mesenteric and axillary lymph node samples were taken and the concentrations of tacrolimus were measured to evaluate pharmacokinetic characteristics and the lymphatic delivery effects. The optimized SEDDS droplets were approximately 40 nm in size and stable enough to endure gastric pH environments. The release rate of tacrolimus from SEDDS was significantly higher than that from the commercial capsule. The bioavailability of tacrolimus in SEDDS after oral administration was significantly improved versus that of Prograf®. The lymphatic targeting efficiency of the prepared SEDDS formulation showed significantly greater than that of Prograf®. Our research indicates that prepared SEDDS can be an alternative to the conventional oral formulation of tacrolimus. Furthermore, SEDDS should be explored as a potential drug carrier for other lipophilic drugs. PMID:26353739

  7. Cost analysis of two implantable narcotic delivery systems.

    PubMed

    Bedder, M D; Burchiel, K; Larson, A

    1991-08-01

    This survey compares costs of two commonly utilized implantable narcotic delivery systems. The systems are classified into type-I (exteriorized system using the DuPen epidural catheter) and type-II (implanted system using the Synchromed pump). Costs were analyzed by reviewing actual patient hospital financial service records and Homecare vendor quotations. From the perspective of cost analysis alone, we conclude that savings accrue when patients requiring treatment beyond 3 months duration are managed with a type-II implanted system compared with a type-I system with an external pump. PMID:1908884

  8. Direct and indirect radiative effects of aerosols using the coupled system of aerosol HAM module and the Weather Research and Forecasting (WRF) model

    NASA Astrophysics Data System (ADS)

    Mashayekhi, Rabab; Irannejad, Parviz; Feichter, Johann; Akbari Bidokhti, Abbas Ali Ali

    2010-05-01

    The fully coupled aerosol-cloud and radiation WRF-HAM modeling system is presented. The aerosol HAM model is implemented within the chemistry version of WRF modeling system. HAM is based on a "pseudo-modal" approach for representation of the particle size distribution. Aerosols are grouped into four geometrical size classes and two types of mixed and insoluble particles. The aerosol components considered are sulfate, black carbon, particulate organic matter, sea salt and mineral dust. Microphysical processes including nucleation, condensation and coagulation of aerosol particles are considered using the microphysics M7 scheme. Horizontal transport of the aerosol particles is simulated using the advection scheme in WRF. Convective transport and vertical mixing of aerosol particles are also considered in the coupled system. A flux-resistance method is used for dry deposition of aerosol particles. Aerosol sizes and chemical compositions are used to determine the aerosol optical properties. Direct effects of aerosols on incoming shortwave radiation flux are simulated by transferring the aerosol optical parameters to the Goddard shortwave radiation scheme. Indirect effects of aerosols are simulated by using a prognostic treatment of cloud droplet number and adding modules that activate aerosol particles to form cloud droplets. The first and second indirect effects, i.e. the interactions of clouds and incoming solar radiation are implemented in WRF-Chem by linking the simulated cloud droplet number with the Goddard shortwave radiation scheme and the Lin et al. microphysics scheme. The simulations are carried out for a 6-day period from 22 to 28 February 2006 in a domain with 30-km grid spacing, encompassing the south-western Asia, North Africa and some parts of Europe. The results show a negative radiative forcing over most parts of the domain, mainly due to the presence of mineral dust aerosols. The simulations are evaluated using the measured downward radiation in

  9. Steerable/distance enhanced penetrometer delivery system

    SciTech Connect

    Amini, A.; Boyd, G.M.

    1996-12-31

    Characterization, monitoring, and remediation of many of the nation`s highly contaminated sites are high priority at DOE. Penetrometers are often used for rapid characterization of underground contamination (plumes). Because of their heavy weight, use of penetrometer trucks over shallow buried storage tanks is restricted and risky. To close this gap, UTD developed a new position location device for penetrometers, called POLO (POsition LOcator), which provides real- time position location without blocking downhole access for environmental sensors. UTD also developed a system to make penetrometers steerable and capable of deeper penetration. Products of this work is a Steerable Vibratory System, which a relatively lightweight rig capable of greater penetration than traditional penetrometers of the same weight.

  10. Direct current power delivery system and method

    DOEpatents

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

    2016-09-06

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

  11. System modeling speeds clamshell unloader delivery

    SciTech Connect

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

    1995-04-01

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

  12. Sampling port for real time analysis of bioaerosol in whole body exposure system for animal aerosol model development

    PubMed Central

    Saini, Divey; Hopkins, Gregory W.; Chen, Ching-ju; Seay, Sarah A.; Click, Eva M.; Lee, Sunhee; Hartings, Justin M.; Frothingham, Richard

    2010-01-01

    Introduction Multiple factors influence the viability of aerosolized bacteria. The delivery of aerosols is affected by chamber conditions (humidity, temperature, and pressure) and bioaerosol characteristics (particle number, particle size distribution, and viable aerosol concentration). Measurement of viable aerosol concentration and particle size is essential to optimize viability and lung delivery. The Madison chamber is widely used to expose small animals to infectious aerosols. Methods A multiplex sampling port was added to the Madison chamber to measure the chamber conditions and bioaerosol characteristics. Aerosols of three pathogens (Bacillus anthracis, Yersinia pestis, and Mycobacterium tuberculosis) were generated under constant conditions and their bioaerosol characteristics were analyzed. Airborne microbes were captured using an impinger or BioSampler. The particle size distribution of airborne microbes was determined using an aerodynamic particle sizer (APS). Viable aerosol concentration, spray factor (viable aerosol concentration/inoculum concentration), and dose presented to the mouse were calculated. Dose retention efficiency and viable aerosol retention rate were calculated from the sampler titers to determine the efficiency of microbe retention in lungs of mice. Results B. anthracis, Y. pestis, and M. tuberculosis aerosols were sampled through the port. The count mean aerodynamic sizes were 0.98, 0.77, and 0.78 μm with geometric standard deviations of 1.60, 1.90, and 2.37, and viable aerosol concentrations in the chamber were 211, 57, and 1 colony-forming unit (CFU)/mL, respectively. Based on the aerosol concentrations, the doses presented to mice for the three pathogens were 2.5e5, 2.2e4 and 464 CFU. Discussion Using the multiplex sampling port we determined whether the animals were challenged with an optimum bioaerosol based on dose presented and respirable particle size. PMID:20849964

  13. Synthetic Microbes As Drug Delivery Systems

    PubMed Central

    2015-01-01

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

  14. Aerosol-Cloud-Precipitation Interactions in the Climate System

    NASA Astrophysics Data System (ADS)

    Andreae, M. O.

    2015-12-01

    Aerosols serve as cloud condensation nuclei (CCN) and thus have a powerful effect on cloud properties. Increased aerosol concentrations resulting from pollution lead to higher cloud droplet concentrations, but smaller droplet sizes. This in turn affects the physical processes inside clouds that lead to the initiation of precipitation. Depending on a number of factors, including aerosol composition, atmospheric stability, and cloud water content, increasing CCN concentrations may either decrease or increase rainfall. In convective clouds, early rain formation is suppressed, which makes more water and energy available to rise higher in the atmosphere and form ice particles. This may invigorate the dynamics of convection, encourage the formation of hail and lightning, and enhance the transport of materials to the upper troposphere. In turn, cloud processing also affects the concentrations, composition, and distribution of atmospheric aerosols. In order to understand and quantify the effects of air pollution on climate, and precipitation in particular, knowledge of natural abundance and characteristics of aerosols is as essential as the observation of perturbed conditions. I will present recent advances in the conceptual understanding of aerosol-precipitation interactions, as well as results of measurements on aerosol and cloud characteristics in pristine and polluted conditions.

  15. Miniature Videoprobe Hockey Stick Delivery System

    SciTech Connect

    Hale, Lester R.; McMurry, Kyle M.

    1998-06-18

    The present invention is a miniature videoprobe system having a probe termination box, a strong back, and a videoprobe housing. The videoprobe system is able to obtain images from a restricted space at least as small as 0.125 inches while producing a high quality image. The strong back has a hockey stick shape with the probe termination box connecting to the top of the handle-like portion of the hockey stick and the videoprobe housing attaching to the opposite end or nose of the hockey stick shape. The videoprobe housing has a roughly arrowhead shape with two thin steel plates sandwiching the internal components there between. The internal components are connected in series to allow for a minor dimension of the videoprobe housing of 0.110 inches. The internal components include an optics train, a CCD chip, and an electronics package. An electrical signal is transmitted from the electronics package through wiring within an internal channel of the strong back to the probe termination box. The strong back has milled into it multiple internal channels for facilitating the transfer of information, items, or devices between the probe termination box and the videoprobe housing.

  16. Using DNA nanotechnology to produce a drug delivery system

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

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

    PubMed

    Ulker, Zeynep; Erkey, Can

    2014-03-10

    Over the past few decades, advances in "aerogel science" have provoked an increasing interest for these materials in pharmaceutical sciences for drug delivery applications. Because of their high surface areas, high porosities and open pore structures which can be tuned and controlled by manipulation of synthesis conditions, nanostructured aerogels represent a promising class of materials for delivery of various drugs as well as enzymes and proteins. Along with biocompatible inorganic aerogels and biodegradable organic aerogels, more complex systems such as surface functionalized aerogels, composite aerogels and layered aerogels have also been under development and possess huge potential. Emphasis is given to the details of the aerogel synthesis and drug loading methods as well as the influence of synthesis parameters and loading methods on the adsorption and release of the drugs. Owing to their ability to increase the bioavailability of low solubility drugs, to improve both their stability and their release kinetics, there are an increasing number of research articles concerning aerogels in different drug delivery applications. This review presents an up to date overview of the advances in all kinds of aerogel based drug delivery systems which are currently under investigation. PMID:24394377

  18. Dose error analysis for a scanned proton beam delivery system

    NASA Astrophysics Data System (ADS)

    Coutrakon, G.; Wang, N.; Miller, D. W.; Yang, Y.

    2010-12-01

    All particle beam scanning systems are subject to dose delivery errors due to errors in position, energy and intensity of the delivered beam. In addition, finite scan speeds, beam spill non-uniformities, and delays in detector, detector electronics and magnet responses will all contribute errors in delivery. In this paper, we present dose errors for an 8 × 10 × 8 cm3 target of uniform water equivalent density with 8 cm spread out Bragg peak and a prescribed dose of 2 Gy. Lower doses are also analyzed and presented later in the paper. Beam energy errors and errors due to limitations of scanning system hardware have been included in the analysis. By using Gaussian shaped pencil beams derived from measurements in the research room of the James M Slater Proton Treatment and Research Center at Loma Linda, CA and executing treatment simulations multiple times, statistical dose errors have been calculated in each 2.5 mm cubic voxel in the target. These errors were calculated by delivering multiple treatments to the same volume and calculating the rms variation in delivered dose at each voxel in the target. The variations in dose were the result of random beam delivery errors such as proton energy, spot position and intensity fluctuations. The results show that with reasonable assumptions of random beam delivery errors, the spot scanning technique yielded an rms dose error in each voxel less than 2% or 3% of the 2 Gy prescribed dose. These calculated errors are within acceptable clinical limits for radiation therapy.

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

    PubMed Central

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

    2012-01-01

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

  20. Vertical profiles of atmospheric fluorescent aerosols observed by a mutil-channel lidar spectrometer system

    NASA Astrophysics Data System (ADS)

    Huang, Z.; Huang, J.; Zhou, T.; Sugimoto, N.; Bi, J.

    2015-12-01

    Zhongwei Huang1*, Jianping Huang1, Tian Zhou1, Nobuo Sugimoto2, Jianrong Bi1 and Jinsen Shi11Key Laboratory for Semi-Arid Climate Change of the Ministry of Education, College of Atmospheric Sciences, Lanzhou University, Lanzhou, China. 2Atmospheric Environment Division, National Institutes for Environmental Studies, Tsukuba, Japan Email: huangzhongwei@lzu.edu.cn Abstract Atmospheric aerosols have a significant impact on regional and globe climate. The challenge in quantifying aerosol direct radiative forcing and aerosol-cloud interactions arises from large spatial and temporal heterogeneity of aerosol concentrations, compositions, sizes, shape and optical properties (IPCC, 2007). Lidar offers some remarkable advantages for determining the vertical structure of atmospheric aerosols and their related optical properties. To investigate the characterization of atmospheric aerosols (especially bioaerosols) with high spatial and temporal resolution, we developed a Raman/fluorescence/polarization lidar system employed a multi-channel spectrometer, with capabilities of providing measurements of Raman scattering and laser-induced fluorescence excitation at 355 nm from atmospheric aerosols. Meanwhile, the lidar system operated polarization measurements both at 355nm and 532nm wavelengths, aiming to obtain more information of aerosols. It employs a high power pulsed laser and a received telescope with 350mm diameter. The receiver could simultaneously detect a wide fluorescent spectrum about 178 nm with spectral resolution 5.7 nm, mainly including an F/3.7 Crossed Czerny-Turner spectrograph, a grating (1200 gr/mm) and a PMT array with 32 photocathode elements. Vertical structure of fluorescent aerosols in the atmosphere was observed by the developed lidar system at four sites across northwest China, during 2014 spring field observation that conducted by Lanzhou University. It has been proved that the developed lidar could detect the fluorescent aerosols with high temporal and

  1. Assessment of Alternative Student Aid Delivery Systems: Preliminary Specification of the Current System with Program Antecedents.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    Specifications of the current delivery systems of the Pell Grant program, the Guaranteed Student Loan (GSL) program, and campus-based aid programs are provided. The relationship between features of the programs and delivery systems is also examined. The campus-based programs include the Supplemental Educational Opportunity Grant (SEOG) Program,…

  2. Nursing Services Delivery Theory: an open system approach

    PubMed Central

    Meyer, Raquel M; O’Brien-Pallas, Linda L

    2010-01-01

    meyer r.m. & o’brien-pallas l.l. (2010)Nursing services delivery theory: an open system approach. Journal of Advanced Nursing66(12), 2828–2838. Aim This paper is a discussion of the derivation of the Nursing Services Delivery Theory from the application of open system theory to large-scale organizations. Background The underlying mechanisms by which staffing indicators influence outcomes remain under-theorized and unmeasured, resulting in a ‘black box’ that masks the nature and organization of nursing work. Theory linking nursing work, staffing, work environments, and outcomes in different settings is urgently needed to inform management decisions about the allocation of nurse staffing resources in organizations. Data sources A search of CINAHL and Business Source Premier for the years 1980–2008 was conducted using the following terms: theory, models, organization, organizational structure, management, administration, nursing units, and nursing. Seminal works were included. Discussion The healthcare organization is conceptualized as an open system characterized by energy transformation, a dynamic steady state, negative entropy, event cycles, negative feedback, differentiation, integration and coordination, and equifinality. The Nursing Services Delivery Theory proposes that input, throughput, and output factors interact dynamically to influence the global work demands placed on nursing work groups at the point of care in production subsystems. Implications for nursing The Nursing Services Delivery Theory can be applied to varied settings, cultures, and countries and supports the study of multi-level phenomena and cross-level effects. Conclusion The Nursing Services Delivery Theory gives a relational structure for reconciling disparate streams of research related to nursing work, staffing, and work environments. The theory can guide future research and the management of nursing services in large-scale healthcare organizations. PMID:20831573

  3. Development of the Ensemble Navy Aerosol Analysis Prediction System (ENAAPS) and its application of the Data Assimilation Research Testbed (DART) in support of aerosol forecasting

    NASA Astrophysics Data System (ADS)

    Rubin, Juli I.; Reid, Jeffrey S.; Hansen, James A.; Anderson, Jeffrey L.; Collins, Nancy; Hoar, Timothy J.; Hogan, Timothy; Lynch, Peng; McLay, Justin; Reynolds, Carolyn A.; Sessions, Walter R.; Westphal, Douglas L.; Zhang, Jianglong

    2016-03-01

    An ensemble-based forecast and data assimilation system has been developed for use in Navy aerosol forecasting. The system makes use of an ensemble of the Navy Aerosol Analysis Prediction System (ENAAPS) at 1 × 1°, combined with an ensemble adjustment Kalman filter from NCAR's Data Assimilation Research Testbed (DART). The base ENAAPS-DART system discussed in this work utilizes the Navy Operational Global Analysis Prediction System (NOGAPS) meteorological ensemble to drive offline NAAPS simulations coupled with the DART ensemble Kalman filter architecture to assimilate bias-corrected MODIS aerosol optical thickness (AOT) retrievals. This work outlines the optimization of the 20-member ensemble system, including consideration of meteorology and source-perturbed ensemble members as well as covariance inflation. Additional tests with 80 meteorological and source members were also performed. An important finding of this work is that an adaptive covariance inflation method, which has not been previously tested for aerosol applications, was found to perform better than a temporally and spatially constant covariance inflation. Problems were identified with the constant inflation in regions with limited observational coverage. The second major finding of this work is that combined meteorology and aerosol source ensembles are superior to either in isolation and that both are necessary to produce a robust system with sufficient spread in the ensemble members as well as realistic correlation fields for spreading observational information. The inclusion of aerosol source ensembles improves correlation fields for large aerosol source regions, such as smoke and dust in Africa, by statistically separating freshly emitted from transported aerosol species. However, the source ensembles have limited efficacy during long-range transport. Conversely, the meteorological ensemble generates sufficient spread at the synoptic scale to enable observational impact through the ensemble data

  4. Development of the Ensemble Navy Aerosol Analysis Prediction System (ENAAPS) and its application of the Data Assimilation Research Testbed (DART) in support of aerosol forecasting

    NASA Astrophysics Data System (ADS)

    Rubin, J. I.; Reid, J. S.; Hansen, J. A.; Anderson, J. L.; Collins, N.; Hoar, T. J.; Hogan, T.; Lynch, P.; McLay, J.; Reynolds, C. A.; Sessions, W. R.; Westphal, D. L.; Zhang, J.

    2015-10-01

    An ensemble-based forecast and data assimilation system has been developed for use in Navy aerosol forecasting. The system makes use of an ensemble of the Navy Aerosol Analysis Prediction System (ENAAPS) at 1° × 1°, combined with an Ensemble Adjustment Kalman Filter from NCAR's Data Assimilation Research Testbed (DART). The base ENAAPS-DART system discussed in this work utilizes the Navy Operational Global Analysis Prediction System (NOGAPS) meteorological ensemble to drive offline NAAPS simulations coupled with the DART Ensemble Kalman Filter architecture to assimilate bias-corrected MODIS Aerosol Optical Thickness (AOT) retrievals. This work outlines the optimization of the 20-member ensemble system, including consideration of meteorology and source-perturbed ensemble members as well as covariance inflation. Additional tests with 80 meteorological and source members were also performed. An important finding of this work is that an adaptive covariance inflation method, which has not been previously tested for aerosol applications, was found to perform better than a temporally and spatially constant covariance inflation. Problems were identified with the constant inflation in regions with limited observational coverage. The second major finding of this work is that combined meteorology and aerosol source ensembles are superior to either in isolation and that both are necessary to produce a robust system with sufficient spread in the ensemble members as well as realistic correlation fields for spreading observational information. The inclusion of aerosol source ensembles improves correlation fields for large aerosol source regions such as smoke and dust in Africa, by statistically separating freshly emitted from transported aerosol species. However, the source ensembles have limited efficacy during long range transport. Conversely, the meteorological ensemble produces sufficient spread at the synoptic scale to enable observational impact through the ensemble data

  5. Novel delivery systems for postoperative analgesia.

    PubMed

    Palmer, Pamela P; Royal, Mike A; Miller, Ronald D

    2014-03-01

    Moderate-to-severe postoperative pain is usually controlled using a multimodal approach, including opioids. Intravenously administered patient-controlled analgesia (IV PCA) with opioids, popular for over 40 years, enables patients to control their level of analgesia and has advantages over a nurse-administered approach, including more satisfied patients and improved pain relief. Unfortunately, IV PCA has drawbacks such as device programming errors, medication prescribing errors, pump malfunction, limitations on patient mobility, IV patency issues, and transmission of infection. Furthermore, the setup of an infusion pump is often complex, time-consuming, and requires witnessed confirmation. Complicating IV PCA is the problem of commonly used compounds, morphine and hydromorphone, having significantly reduced brain/effector-site permeability and active metabolites, both of which create the risk of delayed adverse events. Novel patient-controlled modalities that incorporate rapid effector site-permeating opioids and non-invasive routes of administration offer great promise to enhance both patient and caregiver experiences with postoperative analgesia systems. PMID:24815968

  6. Feasibility Study For A Spaceborne Ozone/Aerosol Lidar System

    NASA Technical Reports Server (NTRS)

    Campbell, Richard E.; Browell, Edward V.; Ismail, Syed; Dudelzak, Alexander E.; Carswell, Allan I.; Ulitsky, Arkady

    1997-01-01

    Because ozone provides a shield against harmful ultraviolet radiation, determines the temperature profile in the stratosphere, plays important roles in tropospheric chemistry and climate, and is a health risk near the surface, changes in natural ozone layers at different altitudes and their global impact are being intensively researched. Global ozone coverage is currently provided by passive optical and microwave satellite sensors that cannot deliver high spatial resolution measurements and have particular limitations in the troposphere. Vertical profiling DIfferential Absorption Lidars (DIAL) have shown excellent range-resolved capabilities, but these systems have been large, inefficient, and have required continuous technical attention for long term operations. Recently, successful, autonomous DIAL measurements have been performed from a high-altitude aircraft (LASE - Lidar Atmospheric Sensing Experiment), and a space-qualified aerosol lidar system (LITE - Laser In-space Technology Experiment) has performed well on Shuttle. Based on the above successes, NASA and the Canadian Space Agency are jointly studying the feasibility of developing ORACLE (Ozone Research with Advanced Cooperative Lidar Experiments), an autonomously operated, compact DIAL instrument to be placed in orbit using a Pegasus class launch vehicle.

  7. Development and characterization of a resistance spot welding aerosol generator and inhalation exposure system.

    PubMed

    Afshari, Aliakbar; Zeidler-Erdely, Patti C; McKinney, Walter; Chen, Bean T; Jackson, Mark; Schwegler-Berry, Diane; Friend, Sherri; Cumpston, Amy; Cumpston, Jared L; Leonard, H Donny; Meighan, Terence G; Frazer, David G; Antonini, James M

    2014-10-01

    Limited information exists regarding the health risks associated with inhaling aerosols that are generated during resistance spot welding of metals treated with adhesives. Toxicology studies evaluating spot welding aerosols are non-existent. A resistance spot welding aerosol generator and inhalation exposure system was developed. The system was designed by directing strips of sheet metal that were treated with an adhesive to two electrodes of a spot welder. Spot welds were made at a specified distance from each other by a computer-controlled welding gun in a fume collection chamber. Different target aerosol concentrations were maintained within the exposure chamber during a 4-h exposure period. In addition, the exposure system was run in two modes, spark and no spark, which resulted in different chemical profiles and particle size distributions. Complex aerosols were produced that contained both metal particulates and volatile organic compounds (VOCs). Size distribution of the particles was multi-modal. The majority of particles were chain-like agglomerates of ultrafine primary particles. The submicron mode of agglomerated particles accounted for the largest portion of particles in terms of particle number. Metal expulsion during spot welding caused the formation of larger, more spherical particles (spatter). These spatter particles appeared in the micron size mode and accounted for the greatest amount of particles in terms of mass. With this system, it is possible to examine potential mechanisms by which spot welding aerosols can affect health, as well as assess which component of the aerosol may be responsible for adverse health outcomes. PMID:25140455

  8. Yeast retrotransposon particles as antigen delivery systems.

    PubMed

    Kingsman, A J; Burns, N R; Layton, G T; Adams, S E

    1995-05-31

    The development of technologies to produce recombinant proteins for use in the pharmaceutical industry has made substantial advances, in particular in the area of generating antigens containing multiple copies of important immunological regions. One such antigen-carrier system is based on the ability of a protein encoded by the yeast retrotransposon, Ty, to self-assemble into virus-like particles. Ty-fusion proteins retain this ability to form particles, and a range of hybrid VLPs carrying a variety of heterologous antigens have been produced and shown to induce potent immune responses. In particular, hybrid VLPs carrying the core protein p24 of HIV (p24-VLPs) have been shown to induce antibody and T-cell proliferative responses in both experimental animals and human volunteers, and immunization of rabbits with VLPs carrying the principal neutralizing determinant of HIV (V3-VLPs) resulted in the induction of neutralizing antibody responses and T-cell proliferation. Further studies with V3-VLPs have shown that this particulate antigen stimulates enhanced V3-specific lymphoproliferative responses as compared to whole recombinant gp120 or to V3 peptide conjugated to albumin. The V3-VLPs also induce potent CTL responses following immunization of mice in the absence of adjuvant. These responses are MHC class I restricted and are mediated by CD8-positive cells. These observations therefore demonstrate that hybrid Ty-VLPs induce both humoral and cellular immune responses against HIV and suggest that these immunogens may be important in combatting AIDS and other infections. PMID:7625653

  9. Chitosan-based delivery systems for diclofenac delivery: preparation and characterization

    NASA Astrophysics Data System (ADS)

    Dreve, Simina; Kacso, Irina; Bratu, Ioan; Indrea, Emil

    2009-08-01

    The preparation and characterization of novel materials for drug delivery has rapidly gained importance in development of innovative medicine. The paper concerns the uses of chitosan as an excipient in oral formulations and as a drug delivery vehicle for burnt painful injuries. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare liquid release systems as hydrogels and solid release systems as sponges is presented. In this paper the preparation of CTS hydrogels and sponges carrying diclofenac (DCF), as anti-inflammatory drug is reported. The immobilization of DCF in CTS is done by mixing the CTS hydrogel with the anti-inflammatory drug solutions. The concentration of anti-inflammatory drug in the CTS hydrogel generating the sponges was of 57 mg/l, 72 mg/l and 114 mg/l. The CTS sponges with anti-inflammatory drugs were prepared by freeze-drying at -610°C and 0,09 atm. The characterization of the hydrogels and sponges was done by infrared spectra (FTIR) and ultraviolet-visible spectroscopy (UV-VIS). The results indicated the formation of CTS-DCF intermediates. The DCF molecules are forming temporary chelates in CTS hydrogels and sponges and they are compatible with skin or some of biological fluids with satisfactory results.

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

    PubMed

    Haggstrom, David A; Doebbeling, Bradley N

    2011-12-01

    Cancer care quality measurement and system change may serve as a case example for larger possibilities in the health care system related to other diseases. Cancer care quality gaps and variation exist across both technical and patient-centered cancer quality measures, especially among vulnerable populations. There is a need to develop measures that address the following dimensions of quality and its context: disparities, overuse, patient-centeredness, and uncertainty. Developments that may promote system change in cancer care delivery include changes in the information market, organizational accountability, and consumer empowerment. Information market changes include public cancer care quality reporting, enabled by health information exchange, and incentivized by pay-for-performance. Moving organizational accountability, reimbursement, and quality measurement from individual episodes of care to multiple providers providing coordinated cancer care may address quality gaps associated with the fragmentation of care delivery. Consumer empowerment through new technologies, such as personal health records, may lead to the collection of patient-centered quality measures and promote patient self-management. Across all of these developments, leadership and ongoing research to guide informed system changes will be necessary to transform the cancer care delivery system. PMID:20940654

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

    PubMed Central

    Youan, Bi-Botti C.

    2010-01-01

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

  12. The Cleveland Health Network: a new integrated delivery system.

    PubMed

    Roman, L K

    1997-01-01

    CHN and its subsidiary CHN MCO have significantly impacted the Cleveland market place in the two years since their inception. CHN will continue to expand geographically with hospital and physician partners who are committed to providing quality care in the most cost-effective manner. Medical management will continue to be the central focus and over-riding success of the CHN MCO, making this organization extremely attractive to the payer market. The integrated CHN and its medical management focus could become a model for other integrated delivery systems. As the market place continues to experience an increase in managed care and more consolidation of healthcare providers (and in some cases, mergers with payers), more integrated delivery systems will emerge. Senior- and mid-level administrators and managers with operational responsibilities need to take into consideration how their patient access systems will need to be modified to meet the demands of managed care through the formation of integrated delivery systems. How patients access the systems is of critical importance in ensuring financial success, ease of access for the patient, and tracking of appropriate medical care. PMID:10166776

  13. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Aerosols in the Convective Boundary Layer: Radiation Effects on the Coupled Land-Atmosphere System

    NASA Astrophysics Data System (ADS)

    Barbaro, E.; Vila-Guerau Arellano, J.; Ouwersloot, H. G.; Schroter, J.; Donovan, D. P.; Krol, M. C.

    2013-12-01

    We investigate the responses of the surface energy budget and the convective boundary-layer (CBL) dynamics to the presence of aerosols using a combination of observations and numerical simulations. A detailed observational dataset containing (thermo)dynamic variables observed at CESAR (Cabauw Experimental Site for Atmospheric Research) and aerosol information from the European Integrated Project on Aerosol, Cloud, Climate, and Air Quality Interactions (IMPACT/EUCAARI) campaign is employed to design numerical experiments reproducing two prototype clear-sky days characterized by: (i) a well-mixed residual layer above a ground inversion and (ii) a continuously growing CBL. A large-eddy simulation (LES) model and a mixed-layer (MXL) model, both coupled to a broadband radiative transfer code and a land-surface model, are used to study the impacts of aerosol scattering and absorption of shortwave radiation on the land-atmosphere system. We successfully validate our model results using the measurements of (thermo)dynamic variables and aerosol properties for the two different CBL prototypes studied here. Our findings indicate that in order to reproduce the observed surface energy budget and CBL dynamics, information of the vertical structure and temporal evolution of the aerosols is necessary. Given the good agreement between the LES and the MXL model results, we use the MXL model to explore the aerosol effect on the land-atmosphere system for a wide range of optical depths and single scattering albedos. Our results show that higher loads of aerosols decrease irradiance, imposing an energy restriction at the surface. Over the studied well-watered grassland, aerosols reduce the sensible heat flux more than the latent heat flux. As a result, aerosols increase the evaporative fraction. Moreover, aerosols also delay the CBL morning onset and anticipate its afternoon collapse. If also present above the CBL during the morning transition, aerosols maintain a persistent near

  16. Comparison of an Aerosol Assimilation System of MODIS Radiances with AERONET retrievals.

    NASA Astrophysics Data System (ADS)

    Weaver, C.; Chin, M.; da Silva, A.; Ginoux, P.

    2004-12-01

    We present results from a simple off-line assimilation system of the radiances from the 7 MODIS channels that sense atmospheric aerosols. We describe the assimilation cycle. The Goddard Chemistry and Aerosol Radiation Transport Model (GOCART), which is driven by assimilated meteorology, simulates five aerosol types: dust, seasalt, black carbon, organic carbon and sulfate. The forward model takes the aerosol information from the GOCART model and calculates radiances based on optical parameters of the aerosol type, satellite viewing angle and the particle growth from relative humidity. Because the GOCART model is driven by previously assimilated meteorology, these forward model radiances can be directly compared with the observed MODIS level2 radiances. The off-line assimilation system simply adjusts the aerosol loading in the GOCART model so that the observed minus forward model (O-F) radiances agree. Minimal change is made to the GOCART aerosol vertical distribution, size distribution and the ratio of the five different aerosol types. The loading in the GOCART model is updated with new MODIS observations every 6 hours. Since the previously assimilated meteorology provides surface wind speed, we account for radiance sensitivity to wind speed over rough ocean. Over land we use surface albedoes from the MODIS land team kindly provided by Eric Moody. Over ocean the assimilation aerosol optical depths (AOD) compare well with AERONET, over land less so. We compare our results with AERONET retrieved single scattering albedo and effective radius. We also investigate data retention issues in the assimilation. This research is part of an ongoing effort at NASA Goddard to integrate aerosols into the Goddard Modeling and Assimilation Office (GMAO) products.

  17. Near Real Time Vertical Profiles of Clouds and Aerosols from the Cloud-Aerosol Transport System (CATS) on the International Space Station

    NASA Astrophysics Data System (ADS)

    Yorks, J. E.; McGill, M. J.; Nowottnick, E. P.

    2015-12-01

    Plumes from hazardous events, such as ash from volcanic eruptions and smoke from wildfires, can have a profound impact on the climate system, human health and the economy. Global aerosol transport models are very useful for tracking hazardous plumes and predicting the transport of these plumes. However aerosol vertical distributions and optical properties are a major weakness of global aerosol transport models, yet a key component of tracking and forecasting smoke and ash. The Cloud-Aerosol Transport System (CATS) is an elastic backscatter lidar designed to provide vertical profiles of clouds and aerosols while also demonstrating new in-space technologies for future Earth Science missions. CATS has been operating on the Japanese Experiment Module - Exposed Facility (JEM-EF) of the International Space Station (ISS) since early February 2015. The ISS orbit provides more comprehensive coverage of the tropics and mid-latitudes than sun-synchronous orbiting sensors, with nearly a three-day repeat cycle. The ISS orbit also provides CATS with excellent coverage over the primary aerosol transport tracks, mid-latitude storm tracks, and tropical convection. Data from CATS is used to derive properties of clouds and aerosols including: layer height, layer thickness, backscatter, optical depth, extinction, and depolarization-based discrimination of particle type. The measurements of atmospheric clouds and aerosols provided by the CATS payload have demonstrated several science benefits. CATS provides near-real-time observations of cloud and aerosol vertical distributions that can be used as inputs to global models. The infrastructure of the ISS allows CATS data to be captured, transmitted, and received at the CATS ground station within several minutes of data collection. The CATS backscatter and vertical feature mask are part of a customized near real time (NRT) product that the CATS processing team produces within 6 hours of collection. The continuous near real time CATS data

  18. Aerosol delivery of beclin1 enhanced the anti-tumor effect of radiation in the lungs of K-rasLA1 mice.

    PubMed

    Shin, Ji-Young; Lim, Hwang-Tae; Minai-Tehrani, Arash; Noh, Mi-Suk; Kim, Ji-Eun; Kim, Ji-Hye; Jiang, Hu-Lin; Arote, Rohidas; Kim, Doo-Yeol; Chae, Chanhee; Lee, Kee-Ho; Kim, Mi-Sook; Cho, Myung-Haing

    2012-07-01

    Radiotherapy alone has several limitations for treating lung cancer. Inhalation, a non-invasive approach for direct delivery of therapeutic agents to the lung, may help to enhance the therapeutic efficacy of radiation. Up-regulating beclin1, known as a tumor suppressor gene that plays a major role in autophagy, may sensitize tumors and lead to tumor regression in lungs of K-ras(LA1) lung cancer model mice. To minimize the side-effects of radiotherapy, fractionated exposures (five times, 24-h interval) with low dose (2 Gy) of radiation to the restricted area (thorax, 2 cm) were conducted. After sensitizing the lungs with radiation, beclin1, complexed with a nano-sized biodegradable poly(ester amine), was prepared and delivered into the murine lung via aerosol three times/week for four weeks. In a histopathological analysis, animals treated with beclin1 and radiation showed highly significant tumor regression and low progression to adenocarcinoma. An increase in the number of autophagic vacuoles and secondary lysosomes was detected. Dissociation of beclin1-bcl2 stimulated autophagy activation and showed a synergistic anti-tumor effect by inhibiting the Akt-mTOR pathway, cell proliferation and angiogenesis. The combination of radiation with non-invasive aerosol delivery of beclin1 may provide a prospect for developing novel therapy regimens applicable in clinics. PMID:22843615

  19. A technical feasibility study of dornase alfa delivery with eFlow® vibrating membrane nebulizers: aerosol characteristics and physicochemical stability.

    PubMed

    Scherer, Thomas; Geller, David E; Owyang, Laura; Tservistas, Marcus; Keller, Manfred; Boden, Norbert; Kesser, Kenneth C; Shire, Steven J

    2011-01-01

    Dornase alfa (Pulmozyme®) is an inhaled mucus-active drug that decreases viscoelasticity of sputum in vitro, improves lung function and reduces respiratory exacerbations in cystic fibrosis (CF) patients of 5 years age and older. The regulatory approval of dornase alfa 15 years ago stipulated that only certain jet nebulizer-compressor combinations should be used to deliver the drug. Since that time there have been significant advances in aerosol delivery technology, including development of electronic perforated vibrating membrane devices. Three independent laboratories studied aerosol characteristics, nebulization time, dose delivery, and stability of dornase alfa after nebulization to determine the feasibility of using perforated vibrating membrane devices to deliver the drug. These studies determined that the eFlow® vibrating membrane technology delivers dornase alfa more rapidly and efficiently than jet nebulizers, and does not affect the physicochemical properties of the drug. These in vitro results demonstrate only the technical feasibility of using vibrating membrane devices to deliver dornase alfa. Clinical studies will be required before any conclusions can be made regarding clinical safety and efficacy of these drug-device combinations for cystic fibrosis. PMID:20533437

  20. The Cloud-Aerosol Transport System (CATS): A New Lidar for Aerosol and Cloud Profiling from the International Space Station

    NASA Technical Reports Server (NTRS)

    Welton, Ellsworth J.; McGill, Mathew J.; Yorks. John E.; Hlavka, Dennis L.; Hart, William D.; Palm, Stephen P.; Colarco, Peter R.

    2012-01-01

    Spaceborne lidar profiling of aerosol and cloud layers has been successfully implemented during a number of prior missions, including LITE, ICESat, and CALIPSO. Each successive mission has added increased capability and further expanded the role of these unique measurements in wide variety of applications ranging from climate, to air quality, to special event monitoring (ie, volcanic plumes). Many researchers have come to rely on the availability of profile data from CALIPSO, especially data coincident with measurements from other A-Train sensors. The CALIOP lidar on CALIPSO continues to operate well as it enters its fifth year of operations. However, active instruments have more limited lifetimes than their passive counterparts, and we are faced with a potential gap in lidar profiling from space if the CALIOP lidar fails before a new mission is operational. The ATLID lidar on EarthCARE is not expected to launch until 2015 or later, and the lidar component of NASA's proposed Aerosols, Clouds, and Ecosystems (ACE) mission would not be until after 2020. Here we present a new aerosol and cloud lidar that was recently selected to provide profiling data from the International Space Station (ISS) starting in 2013. The Cloud-Aerosol Transport System (CATS) is a three wavelength (1064,532,355 nm) elastic backscatter lidar with HSRL capability at 532 nm. Depolarization measurements will be made at all wavelengths. The primary objective of CATS is to continue the CALIPSO aerosol and cloud profile data record, ideally with overlap between both missions and EarthCARE. In addition, the near real time (NRT) data capability ofthe ISS will enable CATS to support operational applications such as aerosol and air quality forecasting and special event monitoring. The HSRL channel will provide a demonstration of technology and a data testbed for direct extinction retrievals in support of ACE mission development. An overview of the instrument and mission will be provided, along with a

  1. Clinical and Community Delivery Systems for Preventive Care

    PubMed Central

    Krist, Alex H.; Shenson, Douglas; Woolf, Steven H.; Bradley, Cathy; Liaw, Winston R.; Rothemich, Stephen F.; Slonim, Amy; Benson, William; Anderson, Lynda A.

    2015-01-01

    Although clinical preventive services (CPS)—screening tests, immunizations, health behavior counseling, and preventive medications—can save lives, Americans receive only half of recommended services. This "prevention gap," if closed, could substantially reduce morbidity and mortality. Opportunities to improve delivery of CPS exist in both clinical and community settings, but these activities are rarely coordinated across these settings, resulting in inefficiencies and attenuated benefits. Through a literature review, semi-structured interviews with 50 national experts, field observations of 53 successful programs, and a national stakeholder meeting, a framework to fully integrate CPS delivery across clinical and community care delivery systems was developed. The framework identifies the necessary participants, their role in care delivery, and the infrastructure, support, and policies necessary to ensure success. Essential stakeholders in integration include clinicians; community members and organizations; spanning personnel and infrastructure; national, state, and local leadership; and funders and purchasers. Spanning personnel and infrastructure are essential to bring clinicians and communities together and to help patients navigate across care settings. The specifics of clinical–community integrations vary depending on the services addressed and the local context. Although broad establishment of effective clinical–community integrations will require substantial changes, existing clinical and community models provide an important starting point. The key policies and elements of the framework are often already in place or easily identified. The larger challenge is for stakeholders to recognize how integration serves their mutual interests and how it can be financed and sustained over time. PMID:24050428

  2. Intracellular Delivery System for Antibody–Peptide Drug Conjugates

    PubMed Central

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

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  4. Porous Tube Plant Nutrient Delivery System development: a device for nutrient delivery in microgravity.

    PubMed

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

    1994-11-01

    The Porous Tube Plant Nutrient Delivery System or PTPNDS (U.S. Patent #4,926,585) has been under development for the past six years with the goal of providing a means for culturing plants in microgravity, specifically providing water and nutrients to the roots. Direct applications of the PTPNDS include plant space biology investigations on the Space Shuttle and plant research for life support in Space Station Freedom. In the past, we investigated various configurations, the suitability of different porous materials, and the effects of pressure and pore size on plant growth. Current work is focused on characterizing the physical operation of the system, examining the effects of solution aeration, and developing prototype configurations for the Plant Growth Unit (PGU), the flight system for the Shuttle mid-deck. Future developments will involve testing on KC-135 parabolic flights, the design of flight hardware and testing aboard the Space Shuttle. PMID:11540217

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

    PubMed Central

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

    Sato, Masahisa; Bhandari, Bishnu; Abe, Osamu

    2001-01-01

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

  7. Characterization of the Aerosol Instrument Package for the In-service Aircraft Global Observing System IAGOS

    NASA Astrophysics Data System (ADS)

    Bundke, Ulrich; Berg, Marcel; Tettig, Frank; Franke, Harald; Petzold, Andreas

    2015-04-01

    The atmospheric aerosol influences the climate twofold via the direct interaction with solar radiation and indirectly effecting microphysical properties of clouds. The latter has the largest uncertainty according to the last IPPC Report. A measured in situ climatology of the aerosol microphysical properties is needed to reduce the reported uncertainty of the aerosol climate impact. The European Research Infrastructure IAGOS (In-service Aircraft for a Global Observing System; www.iagos.org) responds to the increasing requests for long-term, routine in situ observational data by using commercial passenger aircraft as measurement platform. However, scientific instrumentation for the measurement of atmospheric constituents requires major modifications before being deployable aboard in-service passenger aircraft. The IAGOS Aerosol Package (IAGOS-P2C) consists of two modified Butanol based CPCs (Model Grimm 5.410) and one optical particle counter (Model Grimm Sky OPC 1.129). A thermodenuder at 250°C is placed upstream the second CPC, thus the number concentrations of the total aerosol and the non-volatile aerosol fraction is measured. The Sky OPC measures the size distribution in the rage theoretically up to 32 μ m. Because of the inlet cut off diameter of D50=3 μ m we are using the 16 channel mode in the range of 250 nm - 2.5 μ m at 1 Hz resolution. In this presentation the IAGOS Aerosol package is characterized for pressure levels relevant for the planned application, down to cruising level of 150 hPa including the inlet system. In our aerosol lab we have tested the system against standard instrumentation with different aerosol test substances in a long duration test. Particle losses are characterized for the inlet system. In addition first results for airborne measurements are shown from a first field campaign.

  8. Systemic delivery of recombinant proteins by genetically modified myoblasts

    SciTech Connect

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

    1991-12-06

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

  9. Delivery systems for the treatment of degenerated intervertebral discs.

    PubMed

    Blanquer, S B G; Grijpma, D W; Poot, A A

    2015-04-01

    The intervertebral disc (IVD) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production, abnormal enzyme activities and production of pro-inflammatory substances like cytokines. The established treatment strategy for IVD degeneration consists of physiotherapy, pain medication by drug therapy and if necessary surgery. This approach, however, has shown limited success. Alternative strategies to increase and prolong the effects of bioactive agents and to reverse the process of IVD degeneration include the use of delivery systems for drugs, proteins, cells and genes. In view of the specific anatomy and physiology of the IVD and depending on the strategy of the therapy, different delivery systems have been developed which are reviewed in this article. PMID:25451138

  10. Microsponges: A novel strategy for drug delivery system

    PubMed Central

    Kaity, Santanu; Maiti, Sabyasachi; Ghosh, Ashoke Kumar; Pal, Dilipkumar; Ghosh, Animesh; Banerjee, Subham

    2010-01-01

    Microsponges are polymeric delivery systems composed of porous microspheres. They are tiny sponge-like spherical particles with a large porous surface. Moreover, they may enhance stability, reduce side effects and modify drug release favorably. Microsponge technology has many favorable characteristics, which make it a versatile drug delivery vehicle. Microsponge Systems are based on microscopic, polymer-based microspheres that can suspend or entrap a wide variety of substances, and can then be incorporated into a formulated product such as a gel, cream, liquid or powder. The outer surface is typically porous, allowing a sustained flow of substances out of the sphere. Microsponges are porous, polymeric microspheres that are used mostly for topical use and have recently been used for oral administration. Microsponges are designed to deliver a pharmaceutical active ingredient efficiently at the minimum dose and also to enhance stability, reduce side effects, and modify drug release. PMID:22247859

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

    PubMed

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

    2015-05-01

    Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'. PMID:25451137

  12. Magnetic nanoparticle drug delivery systems for targeting tumor

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  13. The ILC Beam Delivery System - Conceptual Design and RD Plans

    SciTech Connect

    Seryi, Andrei; /SLAC

    2005-05-27

    The Beam Delivery System of the ILC has many stringent and sometimes conflicting requirements. To produce luminosity, the beams must be focused to nanometer size. To provide acceptable detector backgrounds, particles far from the beam core must be collimated. Unique beam diagnostics and instrumentation are required to monitor parameters of the colliding beams such as the energy spectrum and polarization. The detector and beamline components must be protected against errant beams. After collision, the beams must also be transported to the beam dumps safely and with acceptable losses. An international team is actively working on the design of the ILC Beam Delivery System in close collaboration. Details of the design, recent progress and remaining challenges will be summarized in this paper.

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

    SciTech Connect

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

    2012-07-01

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

  15. Climate response of the South Asian monsoon system to anthropogenic aerosols

    SciTech Connect

    Ganguly, Dilip; Rasch, Philip J.; Wang, Hailong; Yoon, Jin-Ho

    2012-07-13

    The equilibrium climate response to the total effects (direct, indirect and semi-direct effects) of aerosols arising from anthropogenic and biomass burning emissions on the South Asian summer monsoon system is studied using a coupled atmosphere-slab ocean model. Our results suggest that anthropogenic and biomass burning aerosols generally induce a reduction in mean summer monsoon precipitation over most parts of the Indian subcontinent, strongest along the western coastline of the Indian peninsula and eastern Nepal region, but modest increases also occur over the north western part of the subcontinent. While most of the noted reduction in precipitation is triggered by increased emissions of aerosols from anthropogenic activities, modest increases in the north west are mostly associated with decreases in local emissions of aerosols from forest fire and grass fire sources. Anthropogenic aerosols from outside Asia also contribute to the overall reduction in precipitation but the dominant contribution comes from aerosol sources within Asia. Local emissions play a more important role in the total rainfall response to anthropogenic aerosol sources during the early monsoon period, whereas both local as well as remote emissions of aerosols play almost equally important roles during the later part of the monsoon period. While precipitation responses are primarily driven by local aerosol forcing, regional surface temperature changes over the region are strongly influenced by anthropogenic aerosols from sources further away (non-local changes). Changes in local anthropogenic organic and black carbon emissions by as much as a factor of two (preserving their ratio) produce the same basic signatures in the model's summer monsoon temperature and precipitation responses.

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Allahyari, Mojgan; Mohit, Elham

    2016-03-01

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

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

    PubMed

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

    2015-11-01

    The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. PMID:26455338

  20. Fast and Slow Responses of the South Asian Monsoon System to Anthropogenic Aerosols

    SciTech Connect

    Ganguly, Dilip; Rasch, Philip J.; Wang, Hailong; Yoon, Jin-Ho

    2012-09-25

    Using a global climate model with fully predictive aerosol life cycle, we investigate the fast and slow responses of the South Asian monsoon system to anthropogenic aerosol forcing. Our results show that the feedbacks associated with sea surface temperature (SST) change caused by aerosols play a more important role than the aerosol's direct impact on radiation, clouds and land surface (rapid adjustments) in shaping the total equilibrium climate response of the monsoon system to aerosol forcing. Inhomogeneous SST cooling caused by anthropogenic aerosols eventually reduces the meridional tropospheric temperature gradient and the easterly shear of zonal winds over the region, slowing down the local Hadley cell circulation, decreasing the northward moisture transport, and causing a reduction in precipitation over South Asia. Although total responses in precipitation are closer to the slow responses in general, the fast component dominates over land areas north of 25°N. Our results also show an east-west asymmetry in the fast responses to anthropogenic aerosols causing increases in precipitation west of 80°E but decreases east of it.

  1. The aerosol-monsoon climate system of Asia: A new paradigm

    NASA Astrophysics Data System (ADS)

    Lau, William K. M.

    2016-02-01

    This commentary is based on a series of recent lectures on aerosol-monsoon interactions I gave at the Beijing Normal University in August 2015. A main theme of the lectures is on a new paradigm of "An Aerosol-Monsoon-Climate-System", which posits that aerosol, like rainfall, cloud, and wind, is an integral component of the monsoon climate system, influencing monsoon weather and climate on all timescales. Here, salient issues discussed in my lectures and my personal perspective regarding interactions between atmospheric dynamics and aerosols from both natural and anthropogenic sources are summarized. My hope is that under this new paradigm, we can break down traditional disciplinary barriers, advance a deeper understanding of weather and climate in monsoon regions, as well as entrain a new generation of geoscientists to strive for a sustainable future for one of the most complex and challenging human-natural climate sub-system of the earth.

  2. Immunization by a bacterial aerosol.

    PubMed

    Garcia-Contreras, Lucila; Wong, Yun-Ling; Muttil, Pavan; Padilla, Danielle; Sadoff, Jerry; Derousse, Jessica; Germishuizen, Willem Andreas; Goonesekera, Sunali; Elbert, Katharina; Bloom, Barry R; Miller, Rich; Fourie, P Bernard; Hickey, Anthony; Edwards, David

    2008-03-25

    By manufacturing a single-particle system in two particulate forms (i.e., micrometer size and nanometer size), we have designed a bacterial vaccine form that exhibits improved efficacy of immunization. Microstructural properties are adapted to alter dispersive and aerosol properties independently. Dried "nanomicroparticle" vaccines possess two axes of nanoscale dimensions and a third axis of micrometer dimension; the last one permits effective micrometer-like physical dispersion, and the former provides alignment of the principal nanodimension particle axes with the direction of airflow. Particles formed with this combination of nano- and micrometer-scale dimensions possess a greater ability to aerosolize than particles of standard spherical isotropic shape and of similar geometric diameter. Here, we demonstrate effective application of this biomaterial by using the live attenuated tuberculosis vaccine bacille Calmette-Guérin (BCG). Prepared as a spray-dried nanomicroparticle aerosol, BCG vaccine exhibited high-efficiency delivery and peripheral lung targeting capacity from a low-cost and technically simple delivery system. Aerosol delivery of the BCG nanomicroparticle to normal guinea pigs subsequently challenged with virulent Mycobacterium tuberculosis significantly reduced bacterial burden and lung pathology both relative to untreated animals and to control animals immunized with the standard parenteral BCG. PMID:18344320

  3. Remote Sensing of Aerosol Over the Land from the Earth Observing System MODIS Instrument

    NASA Technical Reports Server (NTRS)

    Kaufman, Yoram; Tanre, Didier; Remer, Lorraine; Einaudi, Franco (Technical Monitor)

    2000-01-01

    On Dec 18, 1999, NASA launched the Moderate-Resolution Imaging Spectroradiometer (MODIS) instrument on the Earth Observing System (EOS) Terra mission, in a spectacular launch. The mission will provide morning (10:30 AM) global observations of aerosol and other related parameters. It will be followed a year later by a MODIS instrument on EOS Aqua for afternoon observations (1:30 PM). MODIS will measure aerosol over land and ocean with its eight 500 m and 250 m channels in the solar spectrum (0-41 to 2.2 micrometers). Over the land MODIS will measure the total column aerosol loading, and distinguish between submicron pollution particles and large soil particles. Standard daily products of resolution of ten kilometers and global mapped eight day and monthly products on a 1x1 degree global scale will be produced routinely and make available for no or small reproduction charge to the international community. Though the aerosol products will not be available everywhere over the land, it is expected that they will be useful for assessments of the presence, sources and transport of urban pollution, biomass burning aerosol, and desert dust. Other measurements from MODIS will supplement the aerosol information, e.g., land use change, urbanization, presence and magnitude of biomass burning fires, and effect of aerosol on cloud microphysics. Other instruments on Terra, e.g. Multi-angle Imaging SpectroRadiometer (MISR) and the Clouds and the Earth's Radiant Energy System (CERES), will also measure aerosol, its properties and radiative forcing in tandem with the MODIS measurements. During the Aqua period, there are plans to launch in 2003 the Pathfinder Instruments for Cloud and Aerosol Spaceborne Observations (PICASSO) mission for global measurements of the aerosol vertical structure, and the PARASOL mission for aerosol characterization. Aqua-MODIS, PICASSO and PARASOL will fly in formation for detailed simultaneous characterization of the aerosol three-dimensional field, which

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

    PubMed

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

    2016-08-20

    In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems. PMID:27173823

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

    PubMed

    Jauhari, Saurabh; Dash, Alekha K

    2006-01-01

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% +/- 0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/- 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell. PMID:16796370

  6. Addition of Tropospheric Chemistry and Aerosols to the NCAR Community Climate System Model

    SciTech Connect

    Cameron-Smith, P; Lamarque, J; Connell, P; Chuang, C; Rotman, D; Taylor, J

    2005-11-14

    Atmospheric chemistry and aerosols have several important roles in climate change. They affect the Earth's radiative balance directly: cooling the earth by scattering sunlight (aerosols) and warming the Earth by trapping the Earth's thermal radiation (methane, ozone, nitrous oxide, and CFCs are greenhouse gases). Atmospheric chemistry and aerosols also impact many other parts of the climate system: modifying cloud properties (aerosols can be cloud condensation nuclei), fertilizing the biosphere (nitrogen species and soil dust), and damaging the biosphere (acid rain and ozone damage). In order to understand and quantify the effects of atmospheric chemistry and aerosols on the climate and the biosphere in the future, it is necessary to incorporate atmospheric chemistry and aerosols into state-of-the-art climate system models. We have taken several important strides down that path. Working with the latest NCAR Community Climate System Model (CCSM), we have incorporated a state-of-the-art atmospheric chemistry model to simulate tropospheric ozone. Ozone is not just a greenhouse gas, it damages biological systems including lungs, tires, and crops. Ozone chemistry is also central to the oxidizing power of the atmosphere, which destroys a lot of pollutants in the atmosphere (which is a good thing). We have also implemented a fast chemical mechanism that has high fidelity with the full mechanism, for significantly reduced computational cost (to facilitate millennium scale simulations). Sulfate aerosols have a strong effect on climate by reflecting sunlight and modifying cloud properties. So in order to simulate the sulfur cycle more fully in CCSM simulations, we have linked the formation of sulfate aerosols to the oxidizing power of the atmosphere calculated by the ozone mechanisms, and to dimethyl sulfide emissions from the ocean ecosystem in the model. Since the impact of sulfate aerosols depends on the relative abundance of other aerosols in the atmosphere, we also

  7. Liposomal drug delivery system from laboratory to clinic.

    PubMed

    Kshirsagar, N A; Pandya, S K; Kirodian, G B; Sanath, S

    2005-01-01

    The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B) remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, Fungisome) drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India. We have therefore

  8. Evaluation of Meteorological and Aerosol Sensing with small Unmanned Aerial Systems

    NASA Astrophysics Data System (ADS)

    Claussen, Johanna; Möhler, Ottmar; Leisner, Thomas; Brooks, Ian; Norris, Sarah; Brooks, Barbara; Hill, Martin; Haunold, Werner; Schrod, Jann; Danielczok, Anja

    2013-04-01

    Atmospheric aerosols have a large impact on the climate system due to their influence on the global radiation budget. Local aerosol sources such as vegetation, (bare) soil or industrial sites have to be quantified with high resolution data to validate aerosol transport models and improve the input for high resolution weather models. Our goal is to evaluate the use of Unmanned Aerial Systems (UAS) as a method for acquisition of high resolution meteorological and aerosol data. During the INUIT measurement campaign in August 2012 at mount Großer Feldberg near Frankfurt, Germany, several flights with different sensor packages were carried out. We measured basic meteorological parameters such as temperature, relative humidity and air pressure with miniaturized onboard sensors. In addition, the Compact Lightweight Aerosol Spectrometer Probe (CLASP) for aerosol size distribution measurement or the Electrostatic Aerosol Collector (EAC) for aerosol sample collection was installed on board. CLASP measures aerosol particles with diameters from 0.17 μm to 9.5 μm in up to 32 channels at a frequency of 10 Hz. The EAC collects air samples at 2 l/min onto a sample holder. After the flight the ice nuclei on the sample holder are activated and counted in the isothermal static diffusion chamber FRIDGE. The results from the INUIT campaign and additional calibration laboratory measurements show that UAS are a valuable platform for miniaturized sensors. The number of ice nuclei was determined with the EAC at 200m above ground level and compared to the reference measurement on the ground.

  9. Gelucire-stabilized nanoparticles as a potential DNA delivery system.

    PubMed

    Oyewumi, Moses O; Wehrung, Daniel; Sadana, Prabodh

    2016-09-01

    Clinical viability of gene delivery systems has been greatly impacted by potential toxicity of the delivery systems. Recently, we reported the nanoparticle (NP) preparation process that employs biocompatible materials such as Gelucire® 44/14 and cetyl alcohol as matrix materials. In the current study, the NP preparation was modified for pDNA loading through: (i) inclusion of cationic lipids (DOTAP or DDAB) with NP matrix materials; or (ii) application of cationic surfactants (CTAB) to generate NPs with desired surface charges for pDNA complexation. Colloidal stability and efficiency of loading pGL3-DR4X2-luciferase plasmid DNA in NPs were verified by gel permeation chromatography. Compared to pDNA alone, all the NPs were effective in preserving pDNA from digestion by DNase. While pDNA loading using CTAB-NPs involved fewer steps compared to DOTAP-NPs and DDAB-NPs, CTAB-NPs were greatly impacted by elevated cytotoxicity level which could be ascribed to the concentrations of CTAB in NP formulations. In vitro transfection studies (in HepG2 cells) based on luciferase expression showed the ranking of cell transfection efficiency as DOTAP-NPs > DDAB-NPs > CTAB-NPs. The overall work provided an initial assessment of gelucire-stabilized NPs as a potential platform for gene delivery. PMID:25915179

  10. Stimulus-responsive "smart" hydrogels as novel drug delivery systems.

    PubMed

    Soppimath, K S; Aminabhavi, T M; Dave, A M; Kumbar, S G; Rudzinski, W E

    2002-09-01

    Recently, there has been a great deal of research activity in the development of stimulus-responsive polymeric hydrogels. These hydrogels are responsive to external or internal stimuli and the response can be observed through abrupt changes in the physical nature of the network. This property can be favorable in many drug delivery applications. The external stimuli can be temperature, pH, ionic strength, ultrasonic sound, electric current, etc. A majority of the literature related to the development of stimulus-responsive drug delivery systems deals with temperature-sensitive poly(N-isopropyl acrylamide) (pNIPAAm) and its various derivatives. However, acrylic-based pH-sensitive systems with weakly acidic/basic functional groups have also been widely studied. Quite recently, glucose-sensitive hydrogels that are responsive to glucose concentration have been developed to monitor the release of insulin. The present article provides a brief introduction and recent developments in the area of stimulus-responsive hydrogels, particularly those that respond to temperature and pH, and their applications in drug delivery. PMID:12378965

  11. Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery

    PubMed Central

    Mather, Laurence E; Woodhouse, Annie; Ward, M Elizabeth; Farr, Stephen J; Rubsamen, Reid A; Eltherington, Lorne G

    1998-01-01

    Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist™, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. Methods Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMist™ and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. Results Plasma concentrations from SmartMist™ were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. Conclusions Fentanyl delivery using SmartMist™ can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae. PMID:9690947

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

    PubMed

    Ajazuddin; Saraf, S

    2010-10-01

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

  13. Development of a Production Ready Automated Wire Delivery System

    NASA Technical Reports Server (NTRS)

    1997-01-01

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

  14. Filamentous Bacteriophage Fd as an Antigen Delivery System in Vaccination

    PubMed Central

    Prisco, Antonella; De Berardinis, Piergiuseppe

    2012-01-01

    Peptides displayed on the surface of filamentous bacteriophage fd are able to induce humoral as well as cell-mediated immune responses, which makes phage particles an attractive antigen delivery system to design new vaccines. The immune response induced by phage-displayed peptides can be enhanced by targeting phage particles to the professional antigen presenting cells, utilizing a single-chain antibody fragment that binds dendritic cell receptor DEC-205. Here, we review recent advances in the use of filamentous phage fd as a platform for peptide vaccines, with a special focus on the use of phage fd as an antigen delivery platform for peptide vaccines in Alzheimer’s Disease and cancer. PMID:22606037

  15. Creating a high-value delivery system for health care.

    PubMed

    Teisberg, Elizabeth O; Wallace, Scott

    2009-01-01

    Health care reform that focuses on improving value enhances both the well-being of patients and the professional satisfaction of physicians. Value in health care is the improvement in health outcomes achieved for patients relative to the money spent. Dramatic and ongoing improvement in the value of health care delivered will require fundamental restructuring of the system. Current efforts to improve safety and reduce waste are truly important but not sufficient. The following three structural changes will drive simultaneous improvement in outcomes and efficiency: (1) reorganizing care delivery into clinically integrated teams defined by patient needs over the full cycle of care; (2) measuring and reporting patient outcomes by clinical teams, across the cycle of care and for identified clusters of medical circumstances; and (3) enabling reimbursement tied to value rather than to quantity of services. Many of these changes require physician leadership. We discuss steps on the journey to value-based care delivery. PMID:19632561

  16. Numerical simulation of iontophoresis in the drug delivery system.

    PubMed

    Filipovic, Nenad; Zivanovic, Marko; Savic, Andrej; Bijelic, Goran

    2016-01-01

    The architecture and composition of stratum corneum act as barriers and limit the diffusion of most drug molecules and ions. Much effort has been made to overcome this barrier and it can be seen that iontophoresis has shown a good effect. Iontophoresis represents the application of low electrical potential to increase the transport of drugs into and across the skin or tissue. Iontophoresis is a noninvasive drug delivery system, and therefore, it is a useful alternative to drug transportation by injection. In this study, we present a numerical model and effects of electrical potential on the drug diffusion in the buccal tissue and the stratum corneum. The initial numerical results are in good comparison with experimental observation. We demonstrate that the application of an applied voltage can greatly improve the efficacy of localized drug delivery as compared to diffusion alone. PMID:26592537

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

    PubMed Central

    Torchilin, Vladimir P.

    2015-01-01

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

  18. Recent advances in pulsatile oral drug delivery systems.

    PubMed

    Politis, Stavros N; Rekkas, Dimitrios M

    2013-08-01

    It is well established that several diseases exhibit circadian behavior, following the relevant rhythm of the physiological functions of the human body. Their study falls in the fields of chronobiology and chronotherapeutics, the latter being essentially the effort of timely matching the treatment with the disease expression, in order to maximize the therapeutic benefits and minimize side effects. Pulsatile drug delivery is one of the pillars of chronopharmaceutics, achieved through dosage form design that allows programmable release of active pharmaceutical ingredients (APIs) to follow the disease's time profile. Its major characteristic is the presence of lag phases, followed by drug release in a variety of rates, immediate, repeated or controlled. The scope of this review is to summarize the recent literature on pulsatile oral drug delivery systems and provide an overview of the ready to use solutions and early stage technologies, focusing on the awarded and pending patents in this technical field during the last few years. PMID:23506535

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

    PubMed

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

    2016-08-30

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

  20. Potential and problems in ultrasound-responsive drug delivery systems.

    PubMed

    Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

    2013-01-01

    Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington's disease, thrombolysis, and disruption of the blood-brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

  1. Potential and problems in ultrasound-responsive drug delivery systems

    PubMed Central

    Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

    2013-01-01

    Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

  2. Impact of Aerosols on Atmospheric Attenuation Loss in Central Receiver Systems: Preprint

    SciTech Connect

    Sengupta, M.; Wagner, M. J.

    2011-08-01

    Atmospheric attenuation loss between the heliostat field and receiver has been recognized as a significant source of loss in Central Receiver Systems. In clear sky situations, extinction of Direct Normal Irradiance (DNI) is primarily by aerosols in the atmosphere. When aerosol loading is high close to the surface the attenuation loss between heliostat and receivers is significantly influenced by the amount of aerosols present on a particular day. This study relates measured DNI to aerosol optical depths close to the surface of the earth. The model developed in the paper uses only measured DNI to estimate the attenuation between heliostat and receiver in a central receiver system. The requirement that only a DNI measurement is available potentially makes the model a candidate for widespread use.

  3. Dose error analysis for a scanned proton beam delivery system.

    PubMed

    Coutrakon, G; Wang, N; Miller, D W; Yang, Y

    2010-12-01

    All particle beam scanning systems are subject to dose delivery errors due to errors in position, energy and intensity of the delivered beam. In addition, finite scan speeds, beam spill non-uniformities, and delays in detector, detector electronics and magnet responses will all contribute errors in delivery. In this paper, we present dose errors for an 8 × 10 × 8 cm(3) target of uniform water equivalent density with 8 cm spread out Bragg peak and a prescribed dose of 2 Gy. Lower doses are also analyzed and presented later in the paper. Beam energy errors and errors due to limitations of scanning system hardware have been included in the analysis. By using Gaussian shaped pencil beams derived from measurements in the research room of the James M Slater Proton Treatment and Research Center at Loma Linda, CA and executing treatment simulations multiple times, statistical dose errors have been calculated in each 2.5 mm cubic voxel in the target. These errors were calculated by delivering multiple treatments to the same volume and calculating the rms variation in delivered dose at each voxel in the target. The variations in dose were the result of random beam delivery errors such as proton energy, spot position and intensity fluctuations. The results show that with reasonable assumptions of random beam delivery errors, the spot scanning technique yielded an rms dose error in each voxel less than 2% or 3% of the 2 Gy prescribed dose. These calculated errors are within acceptable clinical limits for radiation therapy. PMID:21076200

  4. Optimized Delivery System Achieves Enhanced Endomyocardial Stem Cell Retention

    PubMed Central

    Behfar, Atta; Latere, Jean-Pierre; Bartunek, Jozef; Homsy, Christian; Daro, Dorothee; Crespo-Diaz, Ruben J.; Stalboerger, Paul G.; Steenwinckel, Valerie; Seron, Aymeric; Redfield, Margaret M.; Terzic, Andre

    2014-01-01

    Background Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention. Methods and Results Stem cell retention was simulated in silico using one and three-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol – a nickel and titanium alloy displaying shape memory and super-elasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared to a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle, without impact on biocompatibility or safety. Conclusions Modeling guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention. PMID:24326777

  5. Comparison of two in vitro systems to assess cellular effects of nanoparticles-containing aerosols

    PubMed Central

    Fröhlich, Eleonore; Bonstingl, Gudrun; Höfler, Anita; Meindl, Claudia; Leitinger, Gerd; Pieber, Thomas R.; Roblegg, Eva

    2013-01-01

    Inhalation treatment with nanoparticle containing aerosols appears a promising new therapeutic option but new formulations have to be assessed for efficacy and toxicity. We evaluated the utility of a VITROCELL®6 PT-CF + PARI LC SPRINT® Baby Nebulizer (PARI BOY) system compared with a conventional MicroSprayer. A549 cells were cultured in the air–liquid interface, exposed to nanoparticle aerosols and characterized by measurement of transepithelial electrical resistance and staining for tight junction proteins. Deposition and distribution rates of polystyrene particles and of carbon nanotubes on the cells were assessed. In addition, cytotoxicity of aerosols containing polystyrene particles was compared with cytotoxicity of polystyrene particles in suspension tested in submersed cultures. Exposure by itself in both exposure systems did not damage the cells. Deposition rates of aerosolized polystyrene particles were about 700 times and that of carbon nanotubes about 4 times higher in the MicroSprayer than in the VITROCELL®6 PT-CF system. Cytotoxicity of amine-functionalized polystyrene nanoparticles was significantly higher when applied as an aerosol on cell cultured in air–liquid interface culture compared with nanoparticle suspensions tested in submersed culture. The higher cytotoxicity of aerosolized nanoparticles underscores the importance of relevant exposure systems. PMID:22906573

  6. The strategic role of health informatics in integrated delivery systems.

    PubMed

    Currie, G A

    1998-01-01

    Having accurate measures and high-quality health information is critically important for all providers today. Integrated delivery systems are faced with increasing demands for numerous redundant, sometimes conflicting, performance measurement and reporting data from managed care customers, regulators, and accreditors. When implemented independently within each organizational subunit, these measurement systems are costly and difficult to manage. Centralization of all measurement services can maximize the productivity of the costly resources required to deliver them and can achieve efficiencies, cost savings, and a better balance between internal and external resources while collecting information that is of a higher quality for managerial and clinical decision making. PMID:10185721

  7. A clinician-driven home care delivery system.

    PubMed

    August, D A; Faubion, W C; Ryan, M L; Haggerty, R H; Wesley, J R

    1993-12-01

    The financial, entrepreneurial, administrative, and legal forces acting within the home care arena make it difficult for clinicians to develop and operate home care initiatives within an academic setting. HomeMed is a clinician-initiated and -directed home care delivery system wholly owned by the University of Michigan. The advantages of a clinician-directed system include: Assurance that clinical and patient-based factors are the primary determinants of strategic and procedural decisions; Responsiveness of the system to clinician needs; Maintenance of an important role for the referring physician in home care; Economical clinical research by facilitation of protocol therapy in ambulatory and home settings; Reduction of lengths of hospital stays through clinician initiatives; Incorporation of outcome analysis and other research programs into the mission of the system; Clinician commitment to success of the system; and Clinician input on revenue use. Potential disadvantages of a clinician-based system include: Entrepreneurial, financial, and legal naivete; Disconnection from institutional administrative and data management resources; and Inadequate clinician interest and commitment. The University of Michigan HomeMed experience demonstrates a model of clinician-initiated and -directed home care delivery that has been innovative, profitable, and clinically excellent, has engendered broad physician, nurse, pharmacist, and social worker enthusiasm, and has supported individual investigator clinical protocols as well as broad outcomes research initiatives. It is concluded that a clinician-initiated and -directed home care program is feasible and effective, and in some settings may be optimal. PMID:8242586

  8. Current and Future Applications of the GEOS-5 Aerosol Modeling System

    NASA Technical Reports Server (NTRS)

    Colarco, Peter R.; Silva, Arlindo M Da; Burchard-Marchant, Virginie J.; Darmenov, Anton S.; Govindaraju, Ravi C.; Randles, Cynthia A.; Aquila, Valentina; Nowottnick, Edward Paul; Bian, Huisheng

    2013-01-01

    The presentation summarizes current and proposed activities for the GEOS-5 aerosol modeling system. Activities discussed include (i) forecasting and event simulation, (ii) observation simulation, (iii) aerosol-chemistry-climate applications, and (iv) future activities. The document was presented at the 2013 AEROCENTER Annual Meeting held at the GSFC Visitors Center May 31, 2013. The Organizers of the meeting are posting the talks to the public Aerocenter website, after the meeting.

  9. A patchless dissolving microneedle delivery system enabling rapid and efficient transdermal drug delivery

    PubMed Central

    Lahiji, Shayan F.; Dangol, Manita; Jung, Hyungil

    2015-01-01

    Dissolving microneedles (DMNs) are polymeric, microscopic needles that deliver encapsulated drugs in a minimally invasive manner. Currently, DMN arrays are superimposed onto patches that facilitate their insertion into skin. However, due to wide variations in skin elasticity and the amount of hair on the skin, the arrays fabricated on the patch are often not completely inserted and large amount of loaded materials are not delivered. Here, we report “Microlancer”, a novel micropillar based system by which patients can self-administer DMNs and which would also be capable of achieving 97 ± 2% delivery efficiency of the loaded drugs regardless of skin type or the amount of hair on the skin in less than a second. PMID:25604728

  10. Aerosol Layering Characterization Near the Gobi Desert by a Double Polarization Lidar System

    NASA Astrophysics Data System (ADS)

    Zhao, Y.; Boselli, A.; Sannino, A.; Song, C.; Spinelli, N.; Wang, X.

    2016-06-01

    In order to carry out 4-D (space and time) analysis of the atmospheric aerosol distribution and to make a characterization of their properties and time evolution, a transportable multi-wavelength, Elastic/Raman scanning lidar system with angular scanning capability has been realized. The system uses a diode pumped Nd:YAG laser source, specifically designed for this device, and a receiving systems able to detect elastic signals at 355, 532 and 1064 nm and Raman signals at 386, 407 and 607 nm. It also allows to perform aerosol depolarization measurements at both 355nm and 532nm. A first measurement campaign has been carried out in Dunhuang, North-West of China, in the region of the Gobi desert with the aims to study and characterize desert dust at source. Optical properties of aerosol layers developing in the atmosphere have been analyzed and lidar data are discussed in terms of profiles of aerosol backscatter coefficient at 355nm, 532nm, aerosol extinction coefficient at 355nm, aerosol depolarization ratio at 355nm and 532nm and water vapor mixing ratio. Depolarization ratio measured simultaneously at two wavelengths allowed also to study its dependence on the wavelength.

  11. Packaged Au-PPy valves for drug delivery systems

    NASA Astrophysics Data System (ADS)

    Tsai, Han-Kuan A.; Ma, Kuo-Sheng; Zoval, Jim; Kulinsky, Lawrence; Madou, Marc

    2006-03-01

    The most common methods for the drug delivery are swallowing pills or receiving injections. However, formulations that control the rate and period of medicine (i.e., time-release medications) are still problematic. The proposed implantable devices which include batteries, sensors, telemetry, valves, and drug storage reservoirs provide an alternative method for the responsive drug delivery system [1]. Using this device, drug concentration can be precisely controlled which enhances drug efficiency and decreases the side effects. In order to achieve responsive drug delivery, a reliable release valve has to be developed. Biocompatibility, low energy consumption, and minimized leakage are the main requirements for such release method. A bilayer structure composed of Au/PPy film is fabricated as a flap to control the release valve. Optimized potentiostatic control to synthesize polypyrrole (PPy) is presented. The release of miniaturize valve is tested and showed in this paper. A novel idea to simultaneously fabricate the device reservoirs as well as protective packaging is proposed in this paper. The solution of PDMS permeability problem is also mentioned in this article.

  12. Lung-targeted delivery system of curcumin loaded gelatin microspheres.

    PubMed

    Cao, Fengliang; Ding, Buyun; Sun, Min; Guo, Chenyu; Zhang, Lin; Zhai, Guangxi

    2011-11-01

    The purpose of the study is to design and evaluate curcumin loaded gelatin microspheres (C-GMS) for effective drug delivery to the lung. C-GMS was prepared by the emulsification-linkage technique and the formulation was optimized by orthogonal design. The mean encapsulation efficiency and drug loading of the optimal C-GMS were 75.5 ± 3.82 % and 6.15 ± 0.44%, respectively. The C-GMS presented a spherical shape and smooth surface with a mean particle diameter of 18.9 μm. The in vitro drug release behavior of C-GMS followed the first-order kinetics. The tissue distribution showed that the drug concentrations at lung tissue for the C-GMS suspension were significantly higher than those for the curcumin solution, and the Ce for lung was 36.19. Histopathological studies proved C-GMS was efficient and safe to be used as a passive targeted drug delivery system to the lung. Hence, C-GMS has a great potential for the targeted delivery of curcumin to the lung. PMID:21812751

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

    PubMed

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

    2015-01-01

    Gemini surfactants have been extensively used for in vitro gene delivery. Amino acid-derived gemini surfactants combine the special aggregation properties characteristic of the gemini surfactants with high biocompatibility and biodegradability. In this work, novel serine-derived gemini surfactants, differing in alkyl chain lengths and in the linker group bridging the spacer to the headgroups (amine, amide and ester), were evaluated for their ability to mediate gene delivery either per se or in combination with helper lipids. Gemini surfactant-based DNA complexes were characterized in terms of hydrodynamic diameter, surface charge, stability in aqueous buffer and ability to protect DNA. Efficient formulations, able to transfect up to 50% of the cells without causing toxicity, were found at very low surfactant/DNA charge ratios (1/1-2/1). The most efficient complexes presented sizes suitable for intravenous administration and negative surface charge, a feature known to preclude potentially adverse interactions with serum components. This work brings forward a new family of gemini surfactants with great potential as gene delivery systems. PMID:25513958

  14. Recent trends in vaccine delivery systems: A review

    PubMed Central

    Saroja, CH; Lakshmi, PK; Bhaskaran, Shyamala

    2011-01-01

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

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

    PubMed

    Panapisal, Vipaporn; Charoensri, Sawitree; Tantituvanont, Angkana

    2012-06-01

    Silymarin is a standardized extract from Silybum marianum seeds, known for its many skin benefits such as antioxidant, anti-inflammatory, and immunomodulatory properties. In this study, the potential of several microemulsion formulations for dermal delivery of silymarin was evaluated. The pseudo-ternary phase diagrams were constructed for the various microemulsion formulations which were prepared using glyceryl monooleate, oleic acid, ethyl oleate, or isopropyl myristate as the oily phase; a mixture of Tween 20®, Labrasol®, or Span 20® with HCO-40® (1:1 ratio) as surfactants; and Transcutol® as a cosurfactant. Oil-in-water microemulsions were selected to incorporate 2% w/w silymarin. After six heating-cooling cycles, physical appearances of all microemulsions were unchanged and no drug precipitation occurred. Chemical stability studies showed that microemulsion containing Labrasol® and isopropyl myristate stored at 40°C for 6 months showed the highest silybin remaining among others. The silybin remainings depended on the type of surfactant and were sequenced in the order of: Labrasol® > Tween 20® > Span 20®. In vitro release studies showed prolonged release for microemulsions when compared to silymarin solution. All release profiles showed the best fits with Higuchi kinetics. Non-occlusive in vitro skin permeation studies showed absence of transdermal delivery of silybin. The percentages of silybin in skin extracts were not significantly different among the different formulations (p > 0.05). Nevertheless, some silybin was detected in the receiver fluid when performing occlusive experiments. Microemulsions containing Labrasol® also were found to enhance silymarin solubility. Other drug delivery systems with occlusive effect could be further developed for dermal delivery of silymarin. PMID:22350738

  16. ECOLOGICAL EFFECTS OF AEROSOL DRIFT FROM A SALTWATER COOLING SYSTEM

    EPA Science Inventory

    The local terrestrial effects of salt aerosol drift from powered spray modules and a mechanical draft cooling tower at Turkey Point, Florida were evaluated through field and controlled exposure studies. Indigenous vegetation, soil and fresh water were sampled over a year long per...

  17. Real-Time Detection Method And System For Identifying Individual Aerosol Particles

    DOEpatents

    Gard, Eric Evan; Fergenson, David Philip

    2005-10-25

    A method and system of identifying individual aerosol particles in real time. Sample aerosol particles are compared against and identified with substantially matching known particle types by producing positive and negative test spectra of an individual aerosol particle using a bipolar single particle mass spectrometer. Each test spectrum is compared to spectra of the same respective polarity in a database of predetermined positive and negative spectra for known particle types and a set of substantially matching spectra is obtained. Finally the identity of the individual aerosol particle is determined from the set of substantially matching spectra by determining a best matching one of the known particle types having both a substantially matching positive spectrum and a substantially matching negative spectrum associated with the best matching known particle type.

  18. High-latitude stratospheric aerosols measured by the SAM II satellite system in 1978 and 1979

    NASA Technical Reports Server (NTRS)

    Mccormick, M. P.; Chu, W. P.; Mcmaster, L. R.; Grams, G. W.; Hamill, P.; Steele, H. M.; Swissler, T. J.; Herman, B. M.; Pepin, T. J.; Russell, P. B.

    1981-01-01

    Results of the first year of data collection by the SAM (Stratospheric Aerosol Measurement) II satellite system are presented. Almost 10,000 profiles of stratospheric aerosol extinction in the Arctic and Antarctic regions are used to construct plots of weekly averaged aerosol extinction versus altitude and time and stratospheric optical depth versus time. Corresponding temperature fields are presented. These data show striking similarities in the aerosol behavior for corresponding seasons. Wintertime polar stratospheric clouds that are strongly correlated with temperature are documented. They are much more prevalent in the Antarctic stratosphere during the cold austral winter and increase the stratospheric optical depths by as much as an order of magnitude for a period of about 2 months. These clouds might represent a sink for stratospheric water vapor and must be considered in the radiative budget for this region and time.

  19. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

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

    PubMed

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

    2012-01-01

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

  2. Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

    PubMed Central

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

    2012-01-01

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

  3. FACTORS AFFECTING THE DEPOSITION OF AEROSOLIZED INSULIN

    EPA Science Inventory

    Abstract
    Background
    The inhalation of insulin for absorption into the bloodstream via the lung seems to be a promising technique for the treatment of diabetes mellitus. A fundamental issue to be resolved in the development of such insulin aerosol delivery systems is their...

  4. Improving our fundamental understanding of the role of aerosol-cloud interactions in the climate system.

    PubMed

    Seinfeld, John H; Bretherton, Christopher; Carslaw, Kenneth S; Coe, Hugh; DeMott, Paul J; Dunlea, Edward J; Feingold, Graham; Ghan, Steven; Guenther, Alex B; Kahn, Ralph; Kraucunas, Ian; Kreidenweis, Sonia M; Molina, Mario J; Nenes, Athanasios; Penner, Joyce E; Prather, Kimberly A; Ramanathan, V; Ramaswamy, Venkatachalam; Rasch, Philip J; Ravishankara, A R; Rosenfeld, Daniel; Stephens, Graeme; Wood, Robert

    2016-05-24

    The effect of an increase in atmospheric aerosol concentrations on the distribution and radiative properties of Earth's clouds is the most uncertain component of the overall global radiative forcing from preindustrial time. General circulation models (GCMs) are the tool for predicting future climate, but the treatment of aerosols, clouds, and aerosol-cloud radiative effects carries large uncertainties that directly affect GCM predictions, such as climate sensitivity. Predictions are hampered by the large range of scales of interaction between various components that need to be captured. Observation systems (remote sensing, in situ) are increasingly being used to constrain predictions, but significant challenges exist, to some extent because of the large range of scales and the fact that the various measuring systems tend to address different scales. Fine-scale models represent clouds, aerosols, and aerosol-cloud interactions with high fidelity but do not include interactions with the larger scale and are therefore limited from a climatic point of view. We suggest strategies for improving estimates of aerosol-cloud relationships in climate models, for new remote sensing and in situ measurements, and for quantifying and reducing model uncertainty. PMID:27222566

  5. Paclitaxel Nano-Delivery Systems: A Comprehensive Review

    PubMed Central

    Ma, Ping; Mumper, Russell J.

    2013-01-01

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

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

    PubMed

    Ma, Ping; Mumper, Russell J

    2013-02-18

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

  7. Lidar System for Airborne Measurement of Clouds and Aerosols

    NASA Technical Reports Server (NTRS)

    McGill, Matthew; Scott, V. Stanley; Izquierdo, Luis Ramos; Marzouk, Joe

    2008-01-01

    A lidar system for measuring optical properties of clouds and aerosols at three wavelengths is depicted. The laser transmitter is based on a Nd:YVO4 laser crystal pumped by light coupled to the crystal via optical fibers from laser diodes that are located away from the crystal to aid in dissipating the heat generated in the diodes and their drive circuits. The output of the Nd:YVO4 crystal has a wavelength of 1064 nm, and is made to pass through frequency-doubling and frequency-tripling crystals. As a result, the net laser output is a collinear superposition of beams at wavelengths of 1064, 532, and 355 nm. The laser operates at a pulse-repetition rate of 5 kHz, emitting per-pulse energies of 50 microJ at 1064 nm, 25 microJ at 532 nm and 50 microJ at 355 nm. An important feature of this system is an integrating sphere located between the laser output and the laser beam expander lenses. The integrating sphere collects light scattered from the lenses. Three energy-monitor detectors are located at ports inside the integrating sphere. Each of these detectors is equipped with filters such that the laser output energy is measured independently for each wavelength. The laser output energy is measured on each pulse to enable the most accurate calibration possible. The 1064-nm and 532-nm photodetectors are, more specifically, single photon-counting modules (SPCMs). When used at 1064 nm, these detectors have approximately 3% quantum efficiency and low thermal noise (fewer than 200 counts per second). When used at 532 nm, the SPCMs have quantum efficiency of about 60%. The photodetector for the 355-nm channel is a photon-counting photomultiplier tube having a quantum efficiency of about 20%. The use of photon-counting detectors is made feasible by the low laser pulse energy. The main advantage of photon-counting is ease of inversion of data without need for complicated calibration schemes like those necessary for analog detectors. The disadvantage of photon-counting detectors

  8. Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery.

    PubMed

    Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

    2016-06-01

    Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely 'NP-gel') with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

  9. Reliability review of the remote tool delivery system locomotor

    SciTech Connect

    Chesser, J.B.

    1999-04-01

    The locomotor being built by RedZone Robotics is designed to serve as a remote tool delivery (RID) system for waste retrieval, tank cleaning, viewing, and inspection inside the high-level waste tanks 8D-1 and 8D-2 at West Valley Nuclear Services (WVNS). The RTD systm is to be deployed through a tank riser. The locomotor portion of the RTD system is designed to be inserted into the tank and is to be capable of moving around the tank by supporting itself and moving on the tank internal structural columns. The locomotor will serve as a mounting platform for a dexterous manipulator arm. The complete RTD system consists of the locomotor, dexterous manipulator arm, cameras, lights, cables, hoses, cable/hose management system, power supply, and operator control station.

  10. THE SUPERCONDUCTION MAGNETS OF THE ILC BEAM DELIVERY SYSTEM.

    SciTech Connect

    PARKER,B.; ANEREELA, M.; ESCALLIE, J.; HE, P.; JAIN, A.; MARONE, A.; NOSOCHKOV, Y.; SERYI, A.

    2007-06-25

    The ILC Reference Design Report was completed early in February 2007. The Magnet Systems Group was formed to translate magnetic field requirements into magnet designs and cost estimates for the Reference Design. As presently configured, the ILC will have more than 13,000 magnetic elements of which more than 2300 will be based on superconducting technology. This paper will describe the major superconducting magnet needs for the ILC as presently determined by the Area Systems Groups, responsible for beam line design, working with the Magnet Systems Group. The superconducting magnet components include Main Linac quadrupoles, Positron Source undulators, Damping Ring wigglers, a complex array of Final Focus superconducting elements in the Beam Delivery System, and large superconducting solenoids in the e{sup +} and e{sup -} Sources, and the Ring to Main Linac lines.

  11. Power Delivery from an Actual Thermoelectric Generation System

    NASA Astrophysics Data System (ADS)

    Kaibe, Hiromasa; Kajihara, Takeshi; Nagano, Kouji; Makino, Kazuya; Hachiuma, Hirokuni; Natsuume, Daisuke

    2014-06-01

    Similar to photovoltaic (PV) and fuel cells, thermoelectric generators (TEGs) supply direct-current (DC) power, essentially requiring DC/alternating current (AC) conversion for delivery as electricity into the grid network. Use of PVs is already well established through power conditioning systems (PCSs) that enable DC/AC conversion with maximum-power-point tracking, which enables commercial use by customers. From the economic, legal, and regulatory perspectives, a commercial PCS for PVs should also be available for TEGs, preferably as is or with just simple adjustment. Herein, we report use of a PV PCS with an actual TEG. The results are analyzed, and proper application for TEGs is proposed.

  12. The Superconducting Magnets of the ILC Beam Delivery System

    SciTech Connect

    Parker, B.; Anerella, M.; Escallier, J.; He, P.; Jain, A.; Marone, A.; Nosochkov, Y.; Seryi, Andrei; /SLAC

    2007-09-28

    The ILC Beam Delivery System (BDS) uses a variety of superconducting magnets to maximize luminosity and minimize background. Compact final focus quadrupoles with multifunction correction coils focus incoming beams to few nanometer spot sizes while focusing outgoing disrupted beams into a separate extraction beam line. Anti-solenoids mitigate effects from overlapping focusing and the detector solenoid field. Far from the interaction point (IP) strong octupoles help minimize IP backgrounds. A low-field but very large aperture dipole is integrated with the detector solenoid to reduce backgrounds from beamstrahlung pairs generated at the IP. Physics requirements and magnetic design solutions for the BDS superconducting magnets are reviewed in this paper.

  13. Rosin: a naturally derived excipient in drug delivery systems.

    PubMed

    Kumar, Shobhit; Gupta, Satish Kumar

    2013-01-01

    Natural polymers are primarily attractive because they are biodegradable, inexpensive, and readily available. The most important benefit of natural polymers is that they are capable for chemical modifications. One such biopolymer, rosin, and its derivatives have been pharmaceutically evaluated as microencapsulating materials, film forming agent and as binding agent in formulation of tablets. They are also employed in formulation of chewing gum bases and cosmetics. This review article provides an overview of pharmaceutical use of rosin and its derivatives as excipient in dosage forms as well as novel drug delivery systems. PMID:23808195

  14. Computer-automated silica aerosol generator and animal inhalation exposure system

    PubMed Central

    McKinney, Walter; Chen, Bean; Schwegler-Berry, Diane; Frazer, Dave G.

    2015-01-01

    Inhalation exposure systems are necessary tools for determining the dose response relationship of inhaled toxicants under a variety of exposure conditions. The objective of this study was to develop an automated computer controlled system to expose small laboratory animals to precise concentrations of uniformly dispersed airborne silica particles. An acoustical aerosol generator was developed which was capable of re-suspending particles from bulk powder. The aerosolized silica output from the generator was introduced into the throat of a venturi tube. The turbulent high-velocity air stream within the venturi tube increased the dispersion of the re-suspended powder. That aerosol was then used to expose small laboratory animals to constant aerosol concentrations, up to 20mg/m3, for durations lasting up to 8h. Particle distribution and morphology of the silica aerosol delivered to the exposure chamber were characterized to verify that a fully dispersed and respirable aerosol was being produced. The inhalation exposure system utilized a combination of airflow controllers, particle monitors, data acquisition devices and custom software with automatic feedback control to achieve constant and repeatable exposure environments. The automatic control algorithm was capable of maintaining median aerosol concentrations to within ±0.2 mg/m3 of a user selected target concentration during exposures lasting from 2 to 8 h. The system was able to reach 95% of the desired target value in <10min during the beginning phase of an exposure. This exposure system provided a highly automated tool for conducting inhalation toxicology studies involving silica particles. PMID:23796015

  15. Aerosol delivery and safety of recombinant human deoxyribonuclease in young children with cystic fibrosis: a bronchoscopic study. Pulmozyme Pediatric Broncoscopy Study Group.

    PubMed

    Wagener, J S; Rock, M J; McCubbin, M M; Hamilton, S D; Johnson, C A; Ahrens, R C

    1998-10-01

    The purpose of this study was to assess the delivery to the lungs and the short-term safety of recombinant human deoxyribonuclease (rhDNase, Pulmozyme) in children with cystic fibrosis younger than 5 years of age compared with older children. Patients between the ages of 3 months and 10 years had bronchoscopic examination with bronchoalveolar lavage (BAL) after administration of an aerosol dose of 2.5 mg of rhDNase. After recovery from the procedure, patients were discharged home for an additional 13 days of rhDNase therapy. During this time adverse events were recorded to assess short-term safety. A total of 98 patients were enrolled, 65 (66%) aged 3 months to 5 years and 33 (34%) aged 5 years to 10 years. Deoxyribonuclease concentrations in BAL fluid were variable (interquartile range, 752 to 3943 micrograms/mL epithelial lining fluid [ELF]) and did not depend on patient age, weight, or height or differ when delivered through a mouthpiece or mask. The median value for the BAL DNA concentration in the younger group was 432 micrograms/mL ELF compared with 703 micrograms/mL ELF in the older patients. This study demonstrates the value of bronchoscopy and BAL for assessing nebulized medication delivery in young children and shows that aerosolized medications can be delivered to and are present in comparable amounts in the lower airways of younger and older children. Exposure to rhDNase appears to be safe over 2 weeks in infants and young children with cystic fibrosis. PMID:9787685

  16. Developing system for delivery of optical radiation in medicobiological researches

    NASA Astrophysics Data System (ADS)

    Loschenov, Victor B.; Taraz, Majid

    2004-06-01

    Methods of optical diagnostics and methods of photodynamic therapy are actively used in medico-biological researches. The system for delivery of optical radiation is one of the key methods in these researches. Usually these systems use flexible optical fibers with diameters from 200 to 1000 micron. Two types of systems for delivery are subdivided, first for diagnostic researches, second for therapeutic procedures. Existing diagnostic catheters, which have most widely applied in medicine, have bifurcated with diameter of the tip equal 1.8 mm. These devices, which are called fiber-optical catheters, satisfy the majority endoscopes researches. However, till now the problem of optical-diagnostics inside tissue is not soled. Especially it is important at diagnostics of a mammary gland, livers, thyroid glands tumor, tumor of a brain and some other studies connected with punctures. In these cases, it is necessary that diameter of fiber-optical catheters be less than one millimeter. This work is devoted to the development of these catheters. Also in clinical procedures such as photodynamic therapy (PDT) and interstitial laser photocoagulation (ILP), cylindrical light diffusing tips are rapidly becoming a popular device for the administration of the desired light dose for the illumination of hollow organs, such as bronchus, trachea and oesophagus. This work is devoted to the development of these catheters.

  17. Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

    PubMed

    Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Herrmann, Paulo S P; Araújo-Moreira, Fernando M; García-Hernández, Mar; Ruiz-Hitzky, Eduardo

    2014-12-30

    New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays. PMID:25455784

  18. Delivery of Probiotics in the Space Food System

    NASA Technical Reports Server (NTRS)

    Castro, S. L.; Ott, C. M.; Douglas, G. L.

    2014-01-01

    The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers during spaceflight, counteracting the immune dysregulation that has been documented in spaceflight. Specifically, the probiotic Lactobacillus acidophilus has been shown to promote health benefits including antagonism towards and inhibition of virulence related gene expression in pathogens, mucosal stimulation of immune cells, and a reduction in the occurrence and duration of cold and flu-like symptoms. The optimum delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. This work proposes to determine whether L. acidophilus is more viable, and therefore more likely to confer immune benefit, when delivered in a capsule form or when delivered in nonfat dry milk powder with a resuscitation opportunity upon rehydration, following 0, 4, and 8 months of storage at -80degC, 4degC, and 22degC, and both prior to and after challenge with simulated gastric and intestinal juices. We hypothesize that the low moisture neutral dairy matrix provided by the nonfat dry milk, and the rehydration step prior to consumption, will extend probiotic viability and stress tolerance compared to a capsule during potential storage conditions in spaceflight and in simulated digestion conditions.

  19. Delivery of Probiotics in the Space Food System

    NASA Technical Reports Server (NTRS)

    Castro, S. L.; Ott, C. M.; Douglas, G. L.

    2014-01-01

    The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers during spaceflight, counteracting the immune dysregulation that has been documented in spaceflight [1]. Specifically, the probiotic Lactobacillus acidophilus has been shown to promote health benefits including antagonism towards and inhibition of virulence related gene expression in pathogens, mucosal stimulation of immune cells, and a reduction in the occurrence and duration of cold and flu-like symptoms [2-5]. The optimum delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. This work proposes to determine whether L. acidophilus is more viable, and therefore more likely to confer immune benefit, when delivered in a capsule form or when delivered in nonfat dry milk powder with a resuscitation opportunity upon rehydration, following 0, 4, and 8 months of storage at -80degC, 4degC, and 22degC, and both prior to and after challenge with simulated gastric and intestinal juices. We hypothesize that the low moisture neutral dairy matrix provided by the nonfat dry milk, and the rehydration step prior to consumption, will extend probiotic viability and stress tolerance compared to a capsule during potential storage conditions in spaceflight and in simulated digestion conditions.

  20. A Universal Delivery System for Percutaneous Heart Valve Implantation.

    PubMed

    Bartosch, Marco; Peters, Heiner; Spriestersbach, Hendrik; O H-Ici, Darach; Berger, Felix; Schmitt, Boris

    2016-09-01

    Transcatheter heart valve implantation is an emerging technology and an alternative to surgical valve replacement. Most existing systems consist of valves sewn into balloon-expandable stents with a delivery catheter functioning with the specific valve only. The aim of this study was to develop a universally applicable delivery system (DS) for plane stents, valves sewn into both balloon-expandable and self-expandable stents and feasible for use with different access routes. A DS was designed and manufactured in five different diameters. The requirements were derived from the implants, the implantation technique and the cardiovascular geometry of the experimental sheep. The combination of a self-expandable Nitinol stent and a jugular access point represented the major challenge as both flexibility and rigidity of the DS were required. To fulfill these contradicting mechanical properties the sheaths were comprised of a soft outer polymer tube with a stainless steel coiled spring inside. Tissue-engineered and pericardial pulmonary valves were implanted. Also polymeric and balloon-expandable stents were delivered to various positions in the vascular system. The initial success rate was 70.5%. After refinement of the DS, a success rate of 83.3% was achieved with the remaining failed implantations resulting from inadequate sizes of the prostheses. PMID:26864537

  1. A Powder Delivery System (PoDS) for Mars in situ Science

    NASA Astrophysics Data System (ADS)

    Bryson, C.; Blake, D.; Saha, C.; Sarrazin, P.

    2004-12-01

    Many instruments proposed for in situ Mars science investigations work best with fine-grained samples of rocks or soils. Such instruments include the mineral analyzer CheMin [1] and any instrument that requires samples having high surface areas (e.g., mass spectrometers, organic analyzers, etc). The Powder Delivery System (PoDS) is designed to deliver powders of selected grain sizes from a sample acquisition device such as an arm-deployed robotic driller or corer to an instrument suite located on the body of a rover/lander. PoDS is capable of size-selective sampling of crushed rocks, soil or drill powder for delivery to instruments that require specific grain sizes (e.g. 5-50 mg of less than150 micron powder for CheMin). Sample material is transported as an aerosol of particles and gas by vacuum advection. In the laboratory a venturi pump driven by compressed air provides the impulse. On Mars, the ambient atmosphere is a source of CO2 that can be captured and compressed by adsorption pumping during diurnal temperature cycling [2]. The lower atmospheric pressure on the surface of Mars (7 torr) will affect fundamental parameters of gas-particle interaction such as Reynolds, Stocks and Knudsen numbers [3]. However, calculations show that the PoDS will operate under both Martian and terrestrial atmospheric conditions. Cyclone separators with appropriate particle size selection ranges remove particles from the aerosol stream. The vortex flow inside the cyclone causes grains larger than a specific size to be collected, while smaller grains remain entrained in the gas. Cyclones are very efficient inertial and centrifugal particle separators with cut sizes (d50) as low as 4 microns. Depending on the particle size ranges desired, a series of cyclones with descending cut sizes may be used, the simplest case being a single cyclone for particle deposition without mass separation. Transmission / membrane filters of appropriate pore sizes may also be used to collect powder from

  2. Alginate based hydrogel as a potential biopolymeric carrier for drug delivery and cell delivery systems: present status and applications.

    PubMed

    Giri, Tapan Kumar; Thakur, Deepa; Alexander, Amit; Ajazuddin; Badwaik, Hemant; Tripathi, Dulal Krishna

    2012-11-01

    Alginate is a non-toxic, biocompatible and biodegradable natural polymer with a number of peculiar physicochemical properties for which it has wide applications in drug delivery and cell delivery systems. Hydrogel formation can be obtained by interactions of anionic alginates with multivalent inorganic cations by simple ionotropic gelation method. Hydrophilic polymeric network of three dimensional cross linked structures of hydrogels absorb substantial amount of water or biological fluids. Among the numerous biomaterials used for hydrogel formation alginate has been and will continue to be one of the most important biomaterial. Therefore, in view of the vast literature support, we focus in this review on alginate - based hydrogel as drug delivery and cell delivery carriers for biomedical applications. Various properties of alginates, their hydrogels and also various techniques used for preparing alginate hydrogels have been reviewed. PMID:22998675

  3. Non-coding RNAs: Therapeutic Strategies and Delivery Systems.

    PubMed

    Ling, Hui

    2016-01-01

    The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer. PMID:27573903

  4. Demonstrated delivery/employment systems for unattended ground sensors

    NASA Astrophysics Data System (ADS)

    Taylor, Robert R.; Bendowski, Michael A.; McFeaters, Ryan C.

    1997-07-01

    This paper describes the payload delivery system developed and proven to deploy an electronic warfare device to specific, predetermined locations on the battlefield. Initially called the Artillery Delivered Expendable Jammer (AD/EXJAM), it is now designated the Air Delivered-Ground (Deployed) Expendable Jammer (AD-G/EXJAM). The initial units were demonstrated from 155 MM artillery; the later units, from UAV's, helicopters and slow moving, fixed wing aircraft. While these two delivery systems were originally designed specifically for the EXJAM system, the concept is directly applicable to unattended ground sensors that require unmanned remote emplacement. Keys to the success of the jammer included design, development and field testing of power supplies, antennas, deployment systems and packaging to allow payloads to withstand high-g impact and other severe environments typically encountered. The artillery deployed systems were designed to be `wooden' rounds needing no special handling and storing. These systems treat the payload as independent elements which are self-ejected from a fired M483A1 or M864 round and are completely automatic upon hitting the ground. The more recent payloads can be delivered from UAV's and include remote control capabilities, increased operating life and increased power output. The present payload is packaged into a cylindrical shape, approximately six inches in diameter and 6.5 inches long and are contained within a carrier, attached to an Unmanned Air Vehicle (UAV) or any other air vehicle. Upon reaching the dispensing point, the release command can be issue by either the UAV or a separate ground control unit in RF contact with the carrier. The carrier then begins a timed dispensing sequence that has been selected for optimum payload emplacement in the target area. New developments include a design and subsystem demonstration of a tactical munitions dispenser variant of the deployment system. Operational characteristics of any specific

  5. Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.

    PubMed

    Saucier-Sawyer, Jennifer K; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J; Zhang, Junwei; Quijano, Elias; Saltzman, W Mark

    2015-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One NP produced significantly higher brain uptake (∼0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects. PMID:26453169

  6. Delivery of dietary triglycerides to Caenorhabditis elegans using lipid nanoparticles: Nanoemulsion-based delivery systems.

    PubMed

    Colmenares, Daniel; Sun, Quancai; Shen, Peiyi; Yue, Yiren; McClements, D Julian; Park, Yeonhwa

    2016-07-01

    The nematode Caenorhabditis elegans is a powerful tool for studying food bioactives on specific biochemical pathways. However, many food bioactives are highly hydrophobic with extremely low water-solubilities, thereby making them difficult to study using C. elegans. The purpose of this study was to develop nanoemulsion-based systems to deliver hydrophobic molecules in a form that could be ingested by C. elegans. Optical microscopy showed that oil-in-water nanoemulsions with a range of particle diameters (40-500nm) could be ingested by C. elegans. The amount of lipid ingested depended on the size and concentration of the nanoparticles. Fatty acid analysis showed incorporation of conjugated linoleic acid and there was a significant reduction in the fat levels of C. elegans when they were incubated with nanoemulsions containing conjugated linoleic acid, which suggested that this hydrophobic lipid was successfully delivered to the nematodes. The incorporation of hydrophobic molecules into nanoemulsion based-delivery systems may therefore enable their activities to be studied using C. elegans. PMID:26920318

  7. Systemic Delivery of Blood-Brain Barrier Targeted Polymeric Nanoparticles Enhances Delivery to Brain Tissue

    PubMed Central

    Saucier-Sawyer, Jennifer K.; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J.; Zhang, Junwei; Quijano, Elias; Saltzman, W. Mark

    2016-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer nanoparticle systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All nanoparticle preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One nanoparticle produced significantly higher brain uptake (~0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad nanoparticles provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing nanoparticle transport across the BBB does not necessarily yield proportional pharmacological effects. PMID:26453169

  8. Code System to Calculate Particle Penetration Through Aerosol Transport Lines.

    1999-07-14

    Version 00 Distribution is restricted to US Government Agencies and Their Contractors Only. DEPOSITION1.03 is an interactive software program which was developed for the design and analysis of aerosol transport lines. Models are presented for calculating aerosol particle penetration through straight tubes of arbitrary orientation, inlets, and elbows. An expression to calculate effective depositional velocities of particles on tube walls is derived. The concept of maximum penetration is introduced, which is the maximum possible penetrationmore » through a sampling line connecting any two points in a three-dimensional space. A procedure to predict optimum tube diameter for an existing transport line is developed. Note that there is a discrepancy in this package which includes the DEPOSITION 1.03 executable and the DEPOSITION 2.0 report. RSICC was unable to obtain other executables or reports.« less

  9. Dual-aureole and sun spectrometer system for airborne measurements of aerosol optical properties.

    PubMed

    Zieger, Paul; Ruhtz, Thomas; Preusker, Rene; Fischer, Jürgen

    2007-12-10

    We have designed an airborne spectrometer system for the simultaneous measurement of the direct sun irradiance and the aureole radiance in two different solid angles. The high-resolution spectral radiation measurements are used to derive vertical profiles of aerosol optical properties. Combined measurements in two solid angles provide better information about the aerosol type without additional and elaborate measuring geometries. It is even possible to discriminate between absorbing and nonabsorbing aerosol types. Furthermore, they allow to apply additional calibration methods and simplify the detection of contaminated data (e.g., by thin cirrus clouds). For the characterization of the detected aerosol type a new index is introduced that is the slope of the aerosol phase function in the forward scattering region. The instrumentation is a flexible modular setup, which has already been successfully applied in airborne and ground-based field campaigns. We describe the setup as well as the calibration of the instrument. In addition, example vertical profiles of aerosol optical properties--including the aureole measurements--are shown and discussed. PMID:18071387

  10. Characterization of a Quadrotor Unmanned Aircraft System for Aerosol-Particle-Concentration Measurements.

    PubMed

    Brady, James M; Stokes, M Dale; Bonnardel, Jim; Bertram, Timothy H

    2016-02-01

    High-spatial-resolution, near-surface vertical profiling of atmospheric chemical composition is currently limited by the availability of experimental platforms that can sample in constrained environments. As a result, measurements of near-surface gradients in trace gas and aerosol particle concentrations have been limited to studies conducted from fixed location towers or tethered balloons. Here, we explore the utility of a quadrotor unmanned aircraft system (UAS) as a sampling platform to measure vertical and horizontal concentration gradients of trace gases and aerosol particles at high spatial resolution (1 m) within the mixed layer (0-100 m). A 3D Robotics Iris+ autonomous quadrotor UAS was outfitted with a sensor package consisting of a two-channel aerosol optical particle counter and a CO2 sensor. The UAS demonstrated high precision in both vertical (±0.5 m) and horizontal positions (±1 m), highlighting the potential utility of quadrotor UAS drones for aerosol- and trace-gas measurements within complex terrain, such as the urban environment, forest canopies, and above difficult-to-access areas such as breaking surf. Vertical profiles of aerosol particle number concentrations, acquired from flights conducted along the California coastline, were used to constrain sea-spray aerosol-emission rates from coastal wave breaking. PMID:26730457

  11. Noble gas storage and delivery system for ion propulsion

    NASA Technical Reports Server (NTRS)

    Back, Dwight Douglas (Inventor); Ramos, Charlie (Inventor)

    2001-01-01

    A method and system for storing and delivering a noble gas for an ion propulsion system where an adsorbent bearing a noble gas is heated within a storage vessel to desorb the noble gas which is then flowed through a pressure reduction device to a thruster assembly. The pressure and flow is controlled using a flow restrictor and low wattage heater which heats an adsorbent bed containing the noble gas propellant at low pressures. Flow rates of 5-60 sccm can be controlled to within about 0.5% or less and the required input power is generally less than 50 W. This noble gas storage and delivery system and method can be used for earth orbit satellites, and lunar or planetary space missions.

  12. Diagnosing delivery problems in the White House Information Distribution System

    SciTech Connect

    Nahabedian, M.; Shrobe, H.

    1996-12-31

    As part of a collaboration with the White House Office of Media Affairs, members of the MIT Artificial Intelligence Laboratory designed a system, called COMLINK, which distributes a daily stream of documents released by the Office of Media Affairs. Approximately 4000 direct subscribers receive information from this service but more than 100,000 people receive the information through redistribution channels. The information is distributed via Email and the World Wide Web. In such a large scale distribution scheme, there is a constant problem of subscriptions becoming invalid because the user`s Email account has terminated. This causes a backwash of hundreds of {open_quotes}bounced mail{close_quotes} messages per day which must be processed by the operators of the COMLINK system. To manage this annoying but necessary task, an expert system named BMES was developed to diagnose the failures of information delivery.

  13. Optical fiber-based photomechanical molecular delivery system

    NASA Astrophysics Data System (ADS)

    Nakano, Koki; Sato, Shunichi; Kawauchi, Satoko; Ashida, Hiroshi; Nishidate, Izumi

    2014-02-01

    Molecular delivery based on nanosecond pulsed laser-induced photomechanical waves (PMWs) enables endoscopic application by using an optical fiber for laser transmission. In our previous fiber system, a laser target, which was a black natural rubber film as a laser absorbing material covered with an optically transparent polyethylene terephthalate disk to confine the laser-induced plasma, was attached to the output end of a 1 mm core diameter quartz fiber. There were two problems in that system: 1) the outer diameter was large (~2.7 mm) and 2) available peak pressure rapidly decreased with increasing pulse number. In this study, we developed a new fiber delivery system to overcome these problems. As a laser absorbing material, we used a cap-type silicone rubber containing carbon black, into which the fiber output end can simply be inserted. The fiber end surface works to confine the laser-induced plasma. The outer diameter of the fiber system was reduced to ~1.4 mm. At an output laser fluence of 1.2 J/cm2, peak pressure of the first PMW pulse exceeded ~40 MPa. With successive 10 laser pulses, decreasing rate of the peak pressure was 22%, which was considerably lower than that with the previous fiber system (82%), enabling generation of at least successive 30 pulses of PMW with the same cap-type target. With this fiber system, we attempted transfer of plasmid DNA encoding EGFP (enhanced green fluorescence protein) to the rat skin as a test tissue in vivo, showing site-selective efficient gene expression.

  14. Studies of Ice Nucleating Aerosol Particles in Arctic Cloud Systems

    NASA Technical Reports Server (NTRS)

    Rogers, David C.; DeMott, Paul J.; Kreidenweis, Sonia M.

    2001-01-01

    The focus of this research is to improve the understanding of ice nucleating aerosol particles (IN) and the role they play in ice formation in Arctic clouds. IN are important for global climate issues in a variety of ways. The primary effect is their role in determining the phase (liquid or solid) of cloud particles. The microscale impact is on cloud particle size, growth rate, shape, fall speed, concentration, radiative properties, and scavenging of gases and aerosols. On a larger scale, ice formation affects the development of precipitation (rate, amount, type, and distribution), latent heat release (rate and altitude), ambient humidity, the persistence of clouds, and cloud albedo. The overall goals of our FIRE 3 research are to characterize the concentrations and variability of Arctic IN during the winter-spring transition, to compare IN measurements with ice concentrations in Arctic clouds, and to examine selected IN samples for particle morphology and chemical there are distinguishable chemical signatures. The results can be combined with other measurements of aerosols, gaseous species, and cloud characteristics in order to understand the processes that determine the phase and concentration of cloud particles.

  15. Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems

    PubMed Central

    Chen, Yulin; Ma, Ping; Gui, Shuangying

    2014-01-01

    Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed. PMID:24995330

  16. Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

    PubMed Central

    Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.

    2011-01-01

    From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

  17. Orange oil stability in spray dry delivery systems.

    PubMed

    Subramaniam, Anandaraman; Veazey, Robert L; Schober, Amanda; Rada, Alison; Rong, Yunhong; van Sleeuwen, Rutger M T; Golding, Robert; Zhang, Suying; Normand, Valery

    2013-09-12

    The oxidation stability of orange oil flavours encapsulated in carbohydrate based spray dry delivery systems is assessed through accelerated shelf life testing, compatible with the physical state of the delivery system. It is demonstrated here that the oxidative shelf life stability is limited by the diffusion of oxygen through the carbohydrate matrix. Determination of the evolution of orange oil oxidation products with time and correlations with simple but accurate sensory data allows for prediction of absolute shelf life. The oxidative shelf life appears to be dependent only on the number average molecular weight of carbohydrates in the matrix and is not affected by the substitution of small sugars (e.g., maltose for sucrose). A maximum of 2 years shelf life at 25 °C is predicted if sugar dimers are the predominant species in the matrix. The drawback to extended oxidative stability is a low physical stability under humid conditions promoting local softening in the sample. Maltose, having low hygroscopicity, improves the physical stability compared to sucrose. The best compromise between physical (caking) and chemical (oxidation) stability is obtained for carbohydrate compositions with number average molecular weight of 560 g mol(-1) that do not contain sucrose (stability against oxidation: 20 months at 25 °C and stability against humidity: 50% RH at 25 °C). PMID:23911456

  18. Development of antimigraine transdermal delivery systems of pizotifen malate.

    PubMed

    Serna-Jiménez, C E; del Rio-Sancho, S; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; López-Castellano, A; Merino, V

    2015-08-15

    The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate. PMID:26196273

  19. Design of a Multiple Drug Delivery System Directed at Periodontitis

    PubMed Central

    Sundararaj, Sharath C.; Thomas, Mark V.; Peyyala, Rebecca; Dziubla, Thomas D.; Puleo, David A.

    2013-01-01

    Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions. PMID:23948165

  20. Advanced drug delivery systems of curcumin for cancer chemoprevention.

    PubMed

    Bansal, Shyam S; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V; Gupta, Ramesh C

    2011-08-01

    Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. PMID:21546540

  1. Microemulsion Drug Delivery System: For Bioavailability Enhancement of Ampelopsin

    PubMed Central

    Solanki, Shailendra Singh; Sarkar, Brajesh; Dhanwani, Rakesh Kumar

    2012-01-01

    Ampelopsin, one of the most common flavonoids, reported to possess numerous pharmacological activities and shows poor aqueous solubility. The purpose of this study was to enhance the dissolution rate and bioavailability of this drug by developing a novel delivery system that is microemulsion (ME) and to study the effect of microemulsion (ME) on the oral bioavailability of ampelopsin. Capmul MCM-based ME formulation with Cremophor EL as surfactant and Transcutol as cosurfactant was developed for oral delivery of ampelopsin. Optimised ME was evaluated for its transparency, viscosity, percentage assay and so forth. Solubilisation capacity of the ME system was also determined. The prepared ME was compared with the pure drug solution and commercially available tablet for in vitro drug release. The optimised ME formulation containing ampelopsin, Capmul MCM (5.5%), Cremophor EL (25%), Transcutol P (8.5%), and distilled water showed higher in vitro drug release, as compared to plain drug suspension and the suspension of commercially available tablet. These results demonstrate the potential use of ME for improving the bioavailability of poor water soluble compounds, such as ampelopsin. PMID:22830055

  2. Pulsatile Release of Parathyroid Hormone from an Implantable Delivery System

    PubMed Central

    Liu, Xiaohua; Pettway, Glenda J.; McCauley, Laurie K.; Ma, Peter X.

    2007-01-01

    Intermittent (pulsatile) administration of parathyroid hormone (PTH) is known to improve bone micro-architecture, mineral density and strength. Therefore, daily injection of PTH has been clinically used for the treatment of osteoporosis. However, this regimen of administration is not convenient and is not a favorable choice of patients. In this study, an implantable delivery system has been developed to achieve pulsatile release of PTH. A well-defined cylindrical device was first fabricated with a biodegradable polymer, poly(lactic acid) (PLLA), using a reverse solid free form fabrication technique. Three-component polyanhydrides composed of sebacic acid, 1,3-bis(p-carboxyphenoxy) propane and poly(ethylene glycol) were synthesized and used as isolation layers. The polyanhydride isolation layers and PTH-loaded alginate layers were then stacked alternately within the delivery device. The gap between the stacked PTH-releasing core and the device frame was filled with PLLA to seal. Multi-pulse PTH release was achieved using the implantable device. The lag time between two adjacent pulses were modulated by the composition and the film thickness of the polyanhydride. The released PTH was demonstrated to be biologically active using an in vitro assay. Timed sequential release of multiple drugs has also been demonstrated. The implantable device holds promise for both systemic and local therapies. PMID:17576005

  3. Smart drug delivery systems: from fundamentals to the clinic.

    PubMed

    Alvarez-Lorenzo, Carmen; Concheiro, Angel

    2014-07-25

    Forty years after the first reports on stimuli-responsive phase transitions in synthetic hydrogels, the first medicines based on responsive components are approaching the market. Sensitiveness to internal or external signals of the body can be achieved by means of materials (mostly polymers, but also lipids and metals) that modify their properties as a function of the intensity of the signal and that enable the transduction into changes in the delivery system that affect its ability to host/release a therapeutic substance. Integration of responsive materials into implantable depots, targetable nanocarriers and even insertable medical devices can endow them with activation-modulated and feedback-regulated control of drug release. This review offers a critical overview of therapeutically-interesting stimuli to trigger drug release and the evolution of responsive materials suitable as functional excipients, illustrated with recent examples of formulations in clinical trials or already commercially available, which can provide a perspective on the current state of the art on smart drug delivery systems. PMID:24805962

  4. Amino acids as cryoprotectants for liposomal delivery systems.

    PubMed

    Mohammed, Afzal R; Coombes, Allan G A; Perrie, Yvonne

    2007-04-01

    Liposomes provide an efficient delivery system for solubilisation and delivery of both small and macro molecules. However, they suffer from the disadvantage of instability when stored as aqueous dispersions. Cryoprotection of the liposomal systems provides an effective approach to overcome poor stability whilst maintaining formulation characteristics, although, the formulation of a freeze-dried product requires the consideration of not only the selection of an appropriate cryoprotectant, but also needs careful consideration of the processing parameters including pre-freezing conditions, primary and secondary drying protocols along with optimisation of cryoprotectant concentration. This current work investigates the application of amino acids as potential cryoprotectants for the stabilisation of liposomes, and results indicate that amino acids show biphasic nature of stabilisation with 4 mol of cryoprotectant per mole of the lipid exhibiting optimum cryoprotection. The investigations of process parameters showed that the pre-freezing temperatures below the glass transition of the amino acids followed by drying for over 6h resulted in stable formulations. Studies investigating the efficiency of drug retention showed that the cryoprotection offered by lysine was similar to that shown by trehalose, suggesting that amino acids act as effective stabilizers. ESEM analysis was carried out to monitor morphology of the rehydrated liposomes. PMID:17317117

  5. Design of a multiple drug delivery system directed at periodontitis.

    PubMed

    Sundararaj, Sharath C; Thomas, Mark V; Peyyala, Rebecca; Dziubla, Thomas D; Puleo, David A

    2013-11-01

    Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions. PMID:23948165

  6. The Smart Drug Delivery System and Its Clinical Potential.

    PubMed

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

  7. Spatiotemporal drug delivery using laser-generated-focused ultrasound system.

    PubMed

    Di, Jin; Kim, Jinwook; Hu, Quanyin; Jiang, Xiaoning; Gu, Zhen

    2015-12-28

    Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation. PMID:26299506

  8. The Smart Drug Delivery System and Its Clinical Potential

    PubMed Central

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

  9. The visualization of surgical smoke produced by energy delivery devices: significance and effectiveness of evacuation systems

    NASA Astrophysics Data System (ADS)

    de Boorder, Tjeerd; Verdaasdonk, Rudolf; Klaessens, John

    2007-02-01

    Devices delivering energy to biological tissues (eg lasers, RF and ultrasound) can induce surgical smoke consisting of particles, vapor, gasses and aerosols. Besides interfering with the view of the surgeon, the smoke is a risk for the health of both the users and patients. In literature, it has been shown that surgical smoke can contain carcinogenic and harmful biological agents. However, the impact on health of the users and patients is widely debated. The use of smoke evacuation systems in the OR is usually governed by economical reason instead of safety issues. A special image enhancement technique is used to study the behavior of smoke and aerosols and the effectiveness of smoke evacuation systems. A back scatter illumination technique using 1 μs light flashes at video rate was applied to image the smoke production of various surgical devices without and with smoke evacuation while ablating biological tissues. The effectiveness of various smoke evacuation devices and strategies were compared. The ablative thermal devices produced smoke but also aerosols. If the thermal energy was delivered in high peak pulses, the presence of aerosols was more significant. Ultrasound based devices produce mainly aerosols. The distance to the target, the opening of the evacuation nozzle and the dimension of aerosols were leading for the effectiveness of the smoke evacuation. The smoke visualization technique has proven an effective tool for study the effectiveness of smoke and aerosols evacuation. The results can contribute to the necessity to use evacuation systems in the OR.

  10. Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

    PubMed Central

    Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

    2013-01-01

    Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

  11. Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety

    PubMed Central

    Donnelly, Ryan F.; Raj Singh, Thakur Raghu; Woolfson, A. David

    2010-01-01

    Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN. PMID:20297904

  12. Spatial service delivery system for smart licensing & enforcement management

    NASA Astrophysics Data System (ADS)

    Wahap, N. A.; Ismail, N. M.; Nor, N. M.; Ahmad, N.; Omar, M. F.; Termizi, A. A. A.; Zainal, D.; Noordin, N. M.; Mansor, S.

    2016-06-01

    Spatial information has introduced a new sense of urgency for a better understanding of the public needs in term of what, when and where they need services and through which devices, platform or physical locations they need them. The objective of this project is to value- add existing license management process for business premises which comes under the responsibility of Local Authority (PBT). Manipulation of geospatial and tracing technology via mobile platform allows enforcement officers to work in real-time, use a standardized system, improve service delivery, and optimize operation management. This paper will augment the scope and capabilities of proposed concept namely, Smart Licensing/Enforcement Management (SLEm). It will review the current licensing and enforcement practice of selected PBT in comparison to the enhanced method. As a result, the new enhanced system is expected to offer a total solution for licensing/enforcement management whilst increasing efficiency and transparency for smart city management and governance.

  13. Preparing a health care delivery system for Space Station

    NASA Technical Reports Server (NTRS)

    Logan, J. S.; Stewart, G. R.

    1985-01-01

    NASA's Space Station is viewed as the beginning of man's permanent presence in space. This paper presents the guidelines being developed by NASA's medical community in preparing a quality, permanent health care delivery system for Space Station. The guidelines will be driven by unique Space Station requirements such as mission duration, crew size, orbit altitude and inclination, EVA frequency and rescue capability. The approach will emphasize developing a health care system that is modular and flexible. It will also incorporate NASA's requirements for growth capability, commonality, maintainability, and advanced technology development. Goals include preventing unnecessary rescue attempts, as well as maintaining the health and safety of the crew. Proper planning will determine the levels of prevention, diagnosis, and treatment necessary to achieve these goals.