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

NASA Astrophysics Data System (ADS)

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

2012-05-01

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

Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol.

PubMed

Ignjatović, Nenad; Uskoković, Vuk; Ajduković, Zorica; Uskoković, Dragan

2013-03-01

Cholecalciferol, vitamin D3, plays an important role in bonemetabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(D,L)-lactide-co-glycolide (HAp/D3/PLGA). Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems.

Pre-filled syringe - a ready-to-use drug delivery system: a review.

PubMed

Ingle, Rahul G; Agarwal, Aayush S

2014-09-01

Fueled by a growing global expectation of the health and medical fields, billions of dollars/euros/pounds are invested every year in the research of new biological and chemical entities. However, little interest is seen in the development of novel drug delivery systems. One such system, pre-filled syringe (PFS), was invented decades ago but is still a rare mode of delivery in many therapeutic segments. This review comprises properties and effects of extractables, leachables and discuss the characteristics of PFS technology; its composition, glass and polymer types, configuration of PFS, advantages over glass, technical and commercial applicability; its significance against patient, industry, quality, environment and cost; and its business potential. We discuss in brief about PFS used in various major and life-threatening disorders and future prospects. It provides showers of knowledge in the field of PFS drug delivery technology to the reader's, industrialist's and researcher's point of view. The PFS drug delivery system offers a wonderful panorama to lifesaving drugs that are currently only available in conventional vials and ampoules in the market. A novel approach of Form Fill Seal technology can be adopted for this particular ready-to-use dosage form also, which opens the new global doors for budding researchers in the field of pre-filled drug delivery system.

Transdermal delivery of scopolamine by natural submicron injectors: in-vivo study in pig.

PubMed

Shaoul, Esther; Ayalon, Ari; Tal, Yossi; Lotan, Tamar

2012-01-01

Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts), comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with T(max) of 30 minutes and C(max) 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery.

Transdermal Delivery of Scopolamine by Natural Submicron Injectors: In-Vivo Study in Pig

PubMed Central

Shaoul, Esther; Ayalon, Ari; Tal, Yossi; Lotan, Tamar

2012-01-01

Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts), comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with Tmax of 30 minutes and Cmax 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery. PMID:22363770

Using exosomes, naturally-equipped nanocarriers, for drug delivery.

PubMed

Batrakova, Elena V; Kim, Myung Soo

2015-12-10

Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell-cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neurodegenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations. Published by Elsevier B.V.

Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

PubMed

Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; Lőbenberg, Raimar; Doschak, Michael R

2015-12-01

Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation. In the following review, we evaluate transdermal drug delivery systems, with a particular focus on delivering therapeutic agents to treat superficial bone pain, notably stress fractures. We further introduce and discuss several small peptide hormones active in bone (such as calcitonins and parathyroid hormone) that have shown potential for transdermal delivery, often under the added augmentation of transdermal drug delivery systems that employ lipo/hydrophilicity, electric charge, and/or microprojection facilitation across the skin barrier.

In vivo evaluation of a self-nanoemulsifying drug delivery system for curcumin.

PubMed

Nazari-Vanani, R; Moezi, L; Heli, H

2017-04-01

Curcumin has attracted particular attention in recent years due to its great variety of beneficial biological and pharmacological activities. However, its efficacy has been limited due to its low bioavailability, and this limitation can be overcome by novel drug delivery systems. Self-nanoemulsifying drug delivery system (SNEDDS) is a novel route to improve oral bioavailability of lipophilic drugs. SNEDDS spontaneously forms fine oil-in-water nanoemulsion by mild agitation. An optimal formula for a SNEDDS comprised ethyl oleate:tween 80:PEG 600 (50:40:10% w/w) with 11.2-nm uniform droplets was developed for curcumin delivery. The SNEDDS was characterized and its loading properties for curcumin were orally evaluated in rat. The results showed a significant increment of 3.95 times in C max , and the curcumin bioavailability was enhanced by 194.2%, compared to the curcumin suspension in water. The development of the SNEDDS formulation had a great potential as a possible alternative for curcumin administration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Staffing Systems of Care for Children and Families: A Report of the Southern Human Resource Development Consortium for Mental Health on Workforce Issues Related to Community-Based Service Delivery for Children and Adolescents with Serious Emotional Disturbance/Mental Illness and Their Families.

ERIC Educational Resources Information Center

Pires, Sheila A.

This report describes the results of a regional needs assessment of workforce issues related to the delivery of community-based services for children and adolescents with serious emotional disturbance or mental illness and their families in a region comprising 12 southern states. The assessment involved a survey of key stakeholders, principally…

Radionuclide-binding compound, a radionuclide delivery system, a method of making a radium complexing compound, a method of extracting a radionuclide, and a method of delivering a radionuclide

DOEpatents

Fisher, Darrell R.; Wai, Chien M.; Chen, Xiaoyuan

2000-01-01

The invention pertains to compounds which specifically bind radionuclides, and to methods of making radionuclide complexing compounds. In one aspect, the invention includes a radionuclide delivery system comprising: a) a calix[n]arene-crown-[m]-ether compound, wherein n is an integer greater than 3, and wherein m is an integer greater than 3, the calix[n]arene-crown-[m]-ether compound comprising at least two ionizable groups; and b) an antibody attached to the calix[n]arene-crown-[m]-ether compound. In another aspect, the invention includes a method of making a radium complexing compound, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising n phenolic hydroxyl groups; b) providing a crown ether precursor, the crown ether precursor comprising a pair of tosylated ends; c) reacting the pair of tosylated ends with a pair of the phenolic hydroxyl groups to convert said pair of phenolic hydroxyl groups to ether linkages, the ether linkages connecting the crown ether precursor to the calix[n]arene to form a calix[n]arene-crown-[m]-ether compound, wherein m is an integer greater than 3; d) converting remaining phenolic hydroxyl groups to esters; e) converting the esters to acids, the acids being proximate a crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound; and f) providing a Ra.sup.2+ ion within the crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound.

Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

PubMed Central

Ignjatović, Nenad; Uskoković, Vuk; Ajduković, Zorica; Uskoković, Dragan

2013-01-01

Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(D,L)-lactide-co-glycolide (HAp/D3/PLGA). Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems. PMID:25382938

Improving health care delivery to aging adults with disabilities: social work with dual eligibles in a climate of health care reform.

PubMed

Bachman, Sara S; Gonyea, Judith G

2012-01-01

Adults aging with disabilities comprise a diverse group. In this article, we identify the prevalence and characteristics of this target population, focusing on adults who are dually eligible for Medicare and Medicaid. We articulate challenges in the delivery of health, social, and support services to adults aging with disabilities, particularly how existing health care policy and financing contributes to fragmentation of care. Finally, we identify opportunities for social workers to advocate for and promote system improvements in the delivery of care for aging adults with disabilities in the current climate of health care reform.

Patenting of nanopharmaceuticals in drug delivery: no small issue.

PubMed

du Toit, Lisa Claire; Pillay, Viness; Choonara, Yahya E; Pillay, Samantha; Harilall, Sheri-lee

2007-01-01

Nanotechnology is a rapidly evolving interdisciplinary field based on the manipulation of matter on a submicron scale, encompassing matter between 1 and 100 nanometers (nm). The currently registered nanotechnology patents comprise 35 countries being involved in the global distribution of these patents. Close to 3000 patents were issued in the USA since 1996 with the term 'nano' in the patents, with a considerable number having application in nanomedicine. The large majority of therapeutic patents are focused on drug delivery systems, highlighting an important application globally. Nanopharmaceutical patents are centered mainly on non-communicable diseases, with cancer receiving the greatest focus, followed by hepatitis. Drug delivery systems employing nanotechnology have the ability to allow superior drug absorption, controlled drug release and reduced side-effects, enhancing the effectiveness of existing drug delivery systems. Nanoparticle-based drug delivery systems may be among the first types of products to generate serious nanotechnology patent disputes as the multi-billion dollar pharmaceutical industry begins to adopt them. This review article aimed to locate patented nanopharmaceuticals in drug delivery online, employing pertinent key terms while searching the patent databases. Awarded and pending patents in the past 20 years pertaining to nanopharmaceutical or nano-enabled systems such as micelles, nanoemulsions, nanogels, liposomes, nanofibres, dendrimer technology and polymer therapeutics are presented in the review article, providing an overview of the diversity of the patent applications.

Engineering Improvements in a Bacterial Therapeutic Delivery System for Breast Cancer

DTIC Science & Technology

2010-09-01

system comprises a nucleotide sequence encoding a toxic or 20 therapeutic RNA (e.g., mRNA, tRNA, rRNA, siRNA, ribozyme , and the like), a protein or an RNA...an RNA molecule (e.g., siRNA, ribozyme and the like, for example). The structures of such therapeutic agents are known and can be adapted to

Efficient dermal delivery of retinyl palmitate: Progressive polarimetry and Raman spectroscopy to evaluate the structure and efficacy.

PubMed

Lee, Jun Bae; Lee, Dong Ryeol; Choi, Nak Cho; Jang, Jihui; Park, Chun Ho; Yoon, Moung Seok; Lee, Miyoung; Won, Kyoungae; Hwang, Jae Sung; Kim, B Moon

2015-10-12

Over the past decades, there has been a growing interest in dermal drug delivery. Although various novel delivery devices and methods have been developed, dermal delivery is still challenging because of problems such as poor drug permeation, instability of vesicles and drug leakage from vesicles induced by fusion of vesicles. To solve the vesicle instability problems in current dermal delivery systems, we developed materials comprised of liquid crystals as a new delivery vehicle of retinyl palmitate and report the characterization of the liquid crystals using a Mueller matrix polarimetry. The stability of the liquid-crystal materials was evaluated using the polarimeter as a novel evaluation tool along with other conventional methods. The dermal delivery of retinyl palmitate was investigated through the use of confocal Raman spectroscopy. The results indicate that the permeation of retinyl palmitate was enhanced by up to 106% compared to that using an ordinary emulsion with retinyl palmitate. Copyright © 2015 Elsevier B.V. All rights reserved.

Directed transport of bacteria-based drug delivery vehicles: bacterial chemotaxis dominates particle shape.

PubMed

Sahari, Ali; Traore, Mahama A; Scharf, Birgit E; Behkam, Bahareh

2014-10-01

Several attenuated and non-pathogenic bacterial species have been demonstrated to actively target diseased sites and successfully deliver plasmid DNA, proteins and other therapeutic agents into mammalian cells. These disease-targeting bacteria can be employed for targeted delivery of therapeutic and imaging cargos in the form of a bio-hybrid system. The bio-hybrid drug delivery system constructed here is comprised of motile Escherichia coli MG1655 bacteria and elliptical disk-shaped polymeric microparticles. The transport direction for these vehicles can be controlled through biased random walk of the attached bacteria in presence of chemoattractant gradients in a process known as chemotaxis. In this work, we utilize a diffusion-based microfluidic platform to establish steady linear concentration gradients of a chemoattractant and investigate the roles of chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles. Our experimental results demonstrate for the first time that bacterial chemotactic response dominates the effect of body shape in extravascular transport; thus, the non-spherical system could be more favorable for drug delivery applications owing to the known benefits of using non-spherical particles for vascular transport (e.g. relatively long circulation time).

Dendrimer-coupled sonophoresis-mediated transdermal drug-delivery system for diclofenac.

PubMed

Huang, Bin; Dong, Wei-Jiang; Yang, Gao-Yi; Wang, Wei; Ji, Cong-Hua; Zhou, Fei-Ni

2015-01-01

The purpose of the present study was to develop a novel transdermal drug-delivery system comprising a polyamidoamine dendrimer coupled with sonophoresis to enhance the permeation of diclofenac (DF) through the skin. The novel transdermal drug-delivery system was developed by using a statistical Plackett-Burman design. Hairless male Wistar rat skin was used for the DF-permeation study. Coupling media concentration, ultrasound-application time, duty cycle, distance from probe to skin, and a third-generation polyamidoamine-dendrimer concentration were selected as independent variables, while in vitro drug release was selected as a dependent variable. Independent variables were found to be statistically significant (P<0.05). DF gel without dendrimer and ultrasound treatment to skin (passive delivery, run 13) showed 56.69 µg/cm(2) cumulative drug permeated through the skin, while the DF-dendrimer gel without sonophoresis treatment (run 14) showed 257.3 µg/cm(2) cumulative drug permeated through the skin after 24 hours. However, when the same gel was applied to sonophoresis-treated skin, drastic permeation enhancement was observed. In the case of run 3, the cumulative drug that permeated through the skin was 935.21 µg/cm(2). It was concluded that dendrimer-coupled sonophoresis-mediated transdermal drug delivery system has the potential to enhance the permeation of DF through the skin.

Targeted self-assembly of functionalized carbon nanotubes on tumors

DOEpatents

Scheinberg, David A.; McDevitt, Michael R.; Villa, Carlos H.; Mulvey, J. Justin

2018-05-22

Provided herein are methods for delivering a molecule in situ to a cell and for treating a cancer via the in situ delivery. The methods comprise contacting or administering to the cell, as two separate components, a morpholino oligonucleotide comprising a targeting moiety followed by a single wall nanotube construct comprising second morpholino oligonucleotides complementary to the first morpholino oligonucleotides and one or both of a therapeutic or diagnostic payload molecule linked to the single wall nanotube construct. Upon self-assembly of a single wall nanotube complex via hybridization of the first morpholino and second complementary morpholino oligonucleotides at the cell, the payload molecule is delivered. Also provided is the two component self-assembly single wall nanotube system and the single wall nanotube construct comprising the second component.

Whether a novel drug delivery system can overcome the problem of biofilms in respiratory diseases?

PubMed

Dua, Kamal; Shukla, Shakti D; Tekade, Rakesh K; Hansbro, Philip M

2017-02-01

Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches. There is very limited information about how the deposition of biofilm on the respiratory devices and lung itself affects the drug delivered, the delivery system, and other implications. The present mini review summarizes the basic introduction to the biofilms and its avoidance using various drug delivery systems with special emphasis on the respiratory diseases. Understanding the approaches, principles, and modes of drug delivery involved in preventing biofilm deposition will be of interest to both biological and formulation scientists, thereby opening avenues to explore the new vistas in biofilm research for identifying better treatments for pulmonary infectious diseases.

System for energy harvesting and/or generation, storage, and delivery

NASA Technical Reports Server (NTRS)

DeGreeff, Jenniffer Leigh (Inventor); Trainor, John T. (Inventor); Fleig, Patrick Franz (Inventor); Lakeman, Charles D. E. (Inventor)

2011-01-01

A device and method for harvesting, generating, storing, and delivering energy to a load, particularly for remote or inaccessible applications. The device preferably comprises one or more energy sources, at least one supercapacitor, at least one rechargeable battery, and a controller. The charging of the energy storage devices and the delivery of power to the load is preferably dynamically varied to maximize efficiency. A low power consumption charge pump circuit is preferably employed to collect power from low power energy sources while also enabling the delivery of higher voltage power to the load. The charging voltage is preferably programmable, enabling one device to be used for a wide range of specific applications.

System for energy harvesting and/or generation, storage, and delivery

NASA Technical Reports Server (NTRS)

DeGreeff, Jenniffer Leigh (Inventor); Trainor, John T. (Inventor); Fleig, Patrick Franz (Inventor); Lakeman, Charles D. E. (Inventor)

2010-01-01

A device and method for harvesting, generating, storing, and delivering energy to a load, particularly for remote or inaccessible applications. The device preferably comprises one or more energy sources, at least one supercapacitor, at least one rechargeable battery, and a controller. The charging of the energy storage devices and the delivery of power to the load is preferably dynamically varied to maximize efficiency. A low power consumption charge pump circuit is preferably employed to collect power from low power energy sources while also enabling the delivery of higher voltage power to the load. The charging voltage is preferably programmable, enabling one device to be used for a wide range of specific applications.

Synthesis and characterization of a multifunctional gold-doxorubicin nanoparticle system for pH triggered intracellular anticancer drug release.

PubMed

Khutale, Ganesh V; Casey, Alan

2017-10-01

A nanoparticle drug carrier system has been developed to alter the cellular uptake and chemotherapeutic performance of an available chemotherapeutic drug. The system comprises of a multifunctional gold nanoparticle based drug delivery system (Au-PEG-PAMAM-DOX) as a novel platform for intracellular delivery of doxorubicin (DOX). Spherical gold nanoparticles were synthesized by a gold chloride reduction, stabilized with thiolated polyethylene glycol (PEG) and then covalently coupled with a polyamidoamine (PAMAM) G4 dendrimer. Further, conjugation of an anti-cancer drug doxorubicin to the dendrimer via amide bond resulted in Au-PEG-PAMAM-DOX drug delivery system. Acellular drug release studies proved that DOX released from Au-PEG-PAMAM-DOX at physiological pH was negligible but it was significantly increased at a weak acidic milieu. The intracellular drug release was monitored with confocal laser scanning microscopy analysis. In vitro viability studies showed an increase in the associated doxorubicin cytotoxicity not attributed to carrier components indicating the efficiency of the doxorubicin was improved, upon conjugation to the nano system. As such it is postulated that the developed pH triggered multifunctional doxorubicin-gold nanoparticle system, could lead to a promising platform for intracellular delivery of variety of anticancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Exhaust gas recirculation system for an internal combustion engine

DOEpatents

Wu, Ko-Jen

2013-05-21

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

Clinical service lines in integrated delivery systems: an initial framework and exploration.

PubMed

Parker, V A; Charns, M P; Young, G J

2001-01-01

The increasing pressures on integrated healthcare delivery systems (IDSs) to provide coordinated and cost-effective care focuses attention on the question of how to best integrate across multiple sites of care. One increasingly common approach to this issue is the development of clinical service lines that integrate specific bundles of services across the operating units of a system. This article presents a conceptual model of service lines and reports results from a descriptive investigation of service line development among members of the Industry Advisory Board--a research consortium comprising IDSs. The experiences of these IDSs (1) provide valuable insights into the range of organizational arrangements and implementation issues that are associated with service line management in healthcare systems and (2) suggest aspects of service line management worthy of further inquiry.

Current Perspectives on Novel Drug Delivery Systems and Therapies for Management of Prostate Cancer: An Inclusive Review.

PubMed

Bhosale, Rohit R; Gangadharappa, H V; Hani, Umme; Ali M Osmani, Riyaz; Vaghela, Rudra; Kulkarni, P K; Koganti, Venkata Sairam

2017-01-01

Prostate cancer (PC) is a prostate gland cells carcinoma, the foremost reason of cancer deaths in men in developed countries, representing most common malignancy in adult males. The key obstacle to achieve practicable therapeutic effect of active drugs and capable hopeful agents including proteins and peptides, and nucleic acid for prostate cancer is the scarcity of targeted drug delivery to cells of prostate cancer. As a result, need for novel systems, strategies or therapeutic approaches to enhance the assortment of active agents meant for prostate cancer becomes an important criterion. Currently cancer research focuses on improving treatment of prostate cancer using various novel drug delivery systems of chemotherapeutic agents. These novel drug delivery systems comprise nanoparticles and liposomes. Also, strategies or therapeutic approaches intended for the prostate cancer include radiation therapy for localized prostate cancer, hormonal therapy for suppressing tumor growth, and gene-and-immunologic therapy. These systems and approaches can deliver the drugs to their selected or targeted cancer cells for the drug release in cancer atmosphere of prostate thereby enhancing the effectiveness of tumor penetration. The objective was to collect and report the recent research findings to manage the PC. Present review encloses existing diverse novel drug delivery systems and approaches intended for the management of PC. The reported miscellaneous novel drug delivery systems along with the diverse therapies are seem to be precise, secure and relatively effective; and in consequence could lead to a new track for obliteration of prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Methods of use for sensor based fluid detection devices

NASA Technical Reports Server (NTRS)

Lewis, Nathan S. (Inventor)

2001-01-01

Methods of use and devices for detecting analyte in fluid. A system for detecting an analyte in a fluid is described comprising a substrate having a sensor comprising a first organic material and a second organic material where the sensor has a response to permeation by an analyte. A detector is operatively associated with the sensor. Further, a fluid delivery appliance is operatively associated with the sensor. The sensor device has information storage and processing equipment, which is operably connected with the device. This device compares a response from the detector with a stored ideal response to detect the presence of analyte. An integrated system for detecting an analyte in a fluid is also described where the sensing device, detector, information storage and processing device, and fluid delivery device are incorporated in a substrate. Methods for use for the above system are also described where the first organic material and a second organic material are sensed and the analyte is detected with a detector operatively associated with the sensor. The method provides for a device, which delivers fluid to the sensor and measures the response of the sensor with the detector. Further, the response is compared to a stored ideal response for the analyte to determine the presence of the analyte. In different embodiments, the fluid measured may be a gaseous fluid, a liquid, or a fluid extracted from a solid. Methods of fluid delivery for each embodiment are accordingly provided.

In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan.

PubMed

Krauland, Alexander H; Leitner, Verena M; Grabovac, Vjera; Bernkop-Schnürch, Andreas

2006-11-01

The aim of this study was the preparation and in vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. 2-Iminothiolane was covalently attached to chitosan. The resulting conjugate (chitosan-TBA) exhibited 304.9 +/- 63.5 micromol thiol groups per gram polymer. Microparticles were prepared via a new precipitation-micronization technique. The microparticulate delivery system comprised insulin, reduced glutathione and chitosan-TBA (Chito-TBA/Ins) or unmodified chitosan (Chito/Ins) and control microparticles were composed of insulin and mannitol (Mannitol/Ins). Due to a hydration process the size of Chito-TBA/Ins and Chito/Ins microparticles increased in phosphate buffer pH 6.8 2.6- and 2.2-fold, respectively. Fluorescent-labeled insulin-loaded chitosan-TBA microparticles showed a controlled release over 4 h. Chito-TBA/Ins administered nasally to rats led to an absolute bioavailability of 6.9 +/- 1.5%. The blood glucose level decreased for more than 2 h and the calculated absolute pharmacological efficacy was 4.9 +/- 1.4%. Chito/Ins, in comparison, displayed a bioavailability of 4.2 +/- 1.8% and a pharmacological efficacy of 0.7 +/- 0.6%. Mannitol/Ins showed a bioavailability of 1.6 +/- 0.4% and no reduction of the blood glucose level at all. According to these findings microparticles comprising chitosan-TBA seem to have substantial higher potential for nasal insulin administration than unmodified chitosan. Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association

Zn(2+)-Triggered Drug Release from Biocompatible Zirconium MOFs Equipped with Supramolecular Gates.

PubMed

Tan, Li-Li; Li, Haiwei; Zhou, Yue; Zhang, Yuanyuan; Feng, Xiao; Wang, Bo; Yang, Ying-Wei

2015-08-01

A new theranostic nanoplatform, comprising of monodisperse zirconium metal-organic frameworks (MOFs) as drug carriers and carboxylatopillar[5]arene-based supramolecular switches as gating entities, is constructed, and controlled drug release triggered by bio-friendly Zn(2+) ions (abundant in synaptic vesicles) and auxiliary thermal stimulus is realized. This on-command drug delivery system exhibits large pore sizes for drug encapsulation, excellent biodegradability and biocompatibility, extremely low cytotoxicity and premature drug release, and superior dual-stimuli responsiveness, opening a new avenue in targeted drug delivery and controlled release of therapeutic agents, especially in the treatment of central nervous system diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimizing novel penetration enhancing hybridized vesicles for augmenting the in-vivo effect of an anti-glaucoma drug.

PubMed

Naguib, Sarah S; Hathout, Rania M; Mansour, Samar

2017-11-01

Usually the topical delivery of ocular drugs poses a great challenge. Accordingly, the work in this study comprised the use of different hybrids of generally regarded as safe (GRAS) oils and surfactants in order to develop and optimize novel acetazolamide (AZD) entrapped-vesicular systems aiming at improving its ocular delivery and reaching better therapeutic outcomes in the treatment of glaucoma. The phospholipid/cholesterol bilayer of the vesicles was enriched with hybrids of Tween 80, Labrasol, Transcutol and Labrafac lipophile WL in different masses and proportions according to a mixture design viz. D-optimal mixture design. Three models were generated comprising three responses: particles size, percentage of entrapment efficiency and amount of drug released after 24 hours (Q24h). The results demonstrated the ability of the penetration enhancing hybrids in modulating the three responses compared to the conventional liposomes. Transmission electron microscope was used to characterize the selected formulations. Sterilization of selected formulations was carried out using gamma radiation and the effect of gamma radiations on entrapment, particle size and in vitro release were studied. The selected sterilized formulations were tested in-vivo on the eyes of albino rabbits in order to evaluate the efficiency of the novel delivery systems on the intra-ocular pressure reduction (IOP) compared to drug solution and the conventional liposomes. The novel formulations proved their efficiency in reducing the IOP to lower values compared to the conventional liposomes, which pose new successful platform for ocular delivery of AZD and other anti-glaucoma drug analogs.

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

PubMed

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

2008-02-04

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

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

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

PubMed

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

2014-01-01

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

Inhibited-coupling HC-PCF based beam-delivery-system for high power green industrial lasers

NASA Astrophysics Data System (ADS)

Chafer, M.; Gorse, A.; Beaudou, B.; Lekiefs, Q.; Maurel, M.; Debord, B.; Gérôme, F.; Benabid, F.

2018-02-01

We report on an ultra-low loss Hollow-Core Photonic Crystal Fiber (HC-PCF) beam delivery system (GLO-GreenBDS) for high power ultra-short pulse lasers operating in the green spectral range (including 515 nm and 532 nm). The GLOBDS- Green combines ease-of-use, high laser-coupling efficiency, robustness and industrial compatible cabling. It comprises a pre-aligned laser-injection head, a sheath-cable protected HC-PCF and a modular fiber-output head. It enables fiber-core gas loading and evacuation in a hermetic fashion. A 5 m long GLO-BDS were demonstrated for a green short pulse laser with a transmission coefficient larger than 80%, and a laser output profile close to single-mode (M2 <1.3).

Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

PubMed

Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

2005-05-01

Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p < 0.05) better bioavailability than the control system displaying a relative bioavailability of 8.1% The 6 kDa LMWH (300 IU) formulation displayed a relative bioavailability of 10.7% in contrast to the control displaying a relative bioavailability of 2.1%. In conclusion, these results suggest that mucoadhesive thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

Elastic liposomes as novel carriers: recent advances in drug delivery

PubMed Central

Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

2017-01-01

Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. PMID:28761343

Delivery of peptide and protein drugs over the blood-brain barrier.

PubMed

Brasnjevic, Ivona; Steinbusch, Harry W M; Schmitz, Christoph; Martinez-Martinez, Pilar

2009-04-01

Peptide and protein (P/P) drugs have been identified as showing great promises for the treatment of various neurodegenerative diseases. A major challenge in this regard, however, is the delivery of P/P drugs over the blood-brain barrier (BBB). Intense research over the last 25 years has enabled a better understanding of the cellular and molecular transport mechanisms at the BBB, and several strategies for enhanced P/P drug delivery over the BBB have been developed and tested in preclinical and clinical-experimental research. Among them, technology-based approaches (comprising functionalized nanocarriers and liposomes) and pharmacological strategies (such as the use of carrier systems and chimeric peptide technology) appear to be the most promising ones. This review combines a comprehensive overview on the current understanding of the transport mechanisms at the BBB with promising selected strategies published so far that can be applied to facilitate enhanced P/P drug delivery over the BBB.

Elastic liposomes as novel carriers: recent advances in drug delivery.

PubMed

Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

2017-01-01

Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields.

Levels of control exerted by the Isc iron-sulfur cluster system on biosynthesis of the formate hydrogenlyase complex.

PubMed

Pinske, Constanze; Jaroschinsky, Monique; Sawers, R Gary

2013-06-01

The membrane-associated formate hydrogenlyase (FHL) complex of bacteria like Escherichia coli is responsible for the disproportionation of formic acid into the gaseous products carbon dioxide and dihydrogen. It comprises minimally seven proteins including FdhF and HycE, the catalytic subunits of formate dehydrogenase H and hydrogenase 3, respectively. Four proteins of the FHL complex have iron-sulphur cluster ([Fe-S]) cofactors. Biosynthesis of [Fe-S] is principally catalysed by the Isc or Suf systems and each comprises proteins for assembly and for delivery of [Fe-S]. This study demonstrates that the Isc system is essential for biosynthesis of an active FHL complex. In the absence of the IscU assembly protein no hydrogen production or activity of FHL subcomponents was detected. A deletion of the iscU gene also resulted in reduced intracellular formate levels partially due to impaired synthesis of pyruvate formate-lyase, which is dependent on the [Fe-S]-containing regulator FNR. This caused reduced expression of the formate-inducible fdhF gene. The A-type carrier (ATC) proteins IscA and ErpA probably deliver [Fe-S] to specific apoprotein components of the FHL complex because mutants lacking either protein exhibited strongly reduced hydrogen production. Neither ATC protein could compensate for the lack of the other, suggesting that they had independent roles in [Fe-S] delivery to complex components. Together, the data indicate that the Isc system modulates FHL complex biosynthesis directly by provision of [Fe-S] as well as indirectly by influencing gene expression through the delivery of [Fe-S] to key regulators and enzymes that ultimately control the generation and oxidation of formate.

Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy.

PubMed

Rey-Funes, Manuel; Larrayoz, Ignacio M; Fernández, Juan C; Contartese, Daniela S; Rolón, Federico; Inserra, Pablo I F; Martínez-Murillo, Ricardo; López-Costa, Juan J; Dorfman, Verónica B; Martínez, Alfredo; Loidl, César F

2016-06-01

Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats (n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue-PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy. Copyright © 2016 the American Physiological Society.

SU-E-T-649: Quality Assurances for Proton Therapy Delivery Equipment

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

Arjomandy, B; Kase, Y; Flanz, J

2015-06-15

Purpose: The number of proton therapy centers has increased dramatically over the past decade. Currently, there is no comprehensive set of guidelines that addresses quality assurance (QA) procedures for the different technologies used for proton therapy. The AAPM has charged task group 224 (TG-224) to provide recommendations for QA required for accurate and safe dose delivery, using existing and next generation proton therapy delivery equipment. Methods: A database comprised of QA procedures and tolerance limits was generated from many existing proton therapy centers in and outside of the US. These consist of proton therapy centers that possessed double scattering, uniformmore » scanning, and pencil beams delivery systems. The diversity in beam delivery systems as well as the existing devices to perform QA checks for different beam parameters is the main subject of TG-224. Based on current practice at the clinically active proton centers participating in this task group, consensus QA recommendations were developed. The methodologies and requirements of the parameters that must be verified for consistency of the performance of the proton beam delivery systems are discussed. Results: TG-224 provides procedures and QA checks for mechanical, imaging, safety and dosimetry requirements for different proton equipment. These procedures are categorized based on their importance and their required frequencies in order to deliver a safe and consistent dose. The task group provides daily, weekly, monthly, and annual QA check procedures with their tolerance limits. Conclusions: The procedures outlined in this protocol provide sufficient information to qualified medical physicists to perform QA checks for any proton delivery system. Execution of these procedures should provide confidence that proton therapy equipment is functioning as commissioned for patient treatment and delivers dose safely and accurately within the established tolerance limits. The report will be published in late 2015.« less

Main chain acid-degradable polymers for the delivery of bioactive materials

DOEpatents

Frechet, Jean M. J. [Oakland, CA; Standley, Stephany M [Evanston, IL; Jain, Rachna [Milpitas, CA; Lee, Cameron C [Cambridge, MA

2012-03-20

Novel main chain acid degradable polymer backbones and drug delivery systems comprised of materials capable of delivering bioactive materials to cells for use as vaccines or other therapeutic agents are described. The polymers are synthesized using monomers that contain acid-degradable linkages cleavable under mild acidic conditions. The main chain of the resulting polymers readily degrade into many small molecules at low pH, but remain relatively stable and intact at physiological pH. The new materials have the common characteristic of being able to degrade by acid hydrolysis under conditions commonly found within the endosomal or lysosomal compartments of cells thereby releasing their payload within the cell. The materials can also be used for the delivery of therapeutics to the acidic regions of tumors and other sites of inflammation.

Nanotechnology applied to treatment of mucopolysaccharidoses.

PubMed

Schuh, Roselena S; Baldo, Guilherme; Teixeira, Helder F

2016-12-01

Mucopolysaccharidoses (MPS) are genetic disorders caused by the accumulation of glycosaminoglycans due to deficiencies in the lysosomal enzymes responsible for their catabolism. Current treatments are not fully effective and are not available for all MPS types. Accordingly, researchers have tested novel therapies for MPS, including nanotechnology-based enzyme delivery systems and gene therapy. In this review, we aim to analyze some of the approaches involving nanotechnology as alternative treatments for MPS. Areas covered: We analyze nanotechnology-based systems, focusing on the biomaterials, such as polymers and lipids, that comprise these nanostructures, and we have highlighted studies that describe their use as enzyme and gene delivery systems for the treatment of MPS diseases. Expert opinion: Some protocols, such as the use of polymer-based systems or nanostructured carriers associated with enzymes and nanotechnology-based carriers for gene therapy, along with combined approaches, seem to be the future of MPS therapy.

Social Cultural Factors Influencing Appointment of Headteachers in Primary Schools in Eldoret East Sub-County, Kenya

ERIC Educational Resources Information Center

Suter, Esther J.

2017-01-01

Headteachers' position is at the critical point of which all the mechanism of Education system: planning, delivery and management rest. The purpose of the study was to investigate social cultural factors influencing appointment of headteachers in primary schools in Eldoret East Sub-County, Uasin Gishu County. The target population comprised of 275…

A nano particle vector comprised of poly lactic-co-glycolic acid and monophosphoryl lipid A and recombinant Mycobacterium avium subsp paratuberculosis peptides stimulate a pro-immune profile in bovine macrophages

USDA-ARS?s Scientific Manuscript database

Current research and development of antigens for vaccination often center on purified recombinant proteins, viral vectored subunits, and synthetic peptides, most of which suffer from poor immunogenicity and are subject to degradation. For these reasons, efficient delivery systems and potent immunost...

Single-step assembly of cationic lipid-polymer hybrid nanoparticles for systemic delivery of siRNA.

PubMed

Yang, Xian-Zhu; Dou, Shuang; Wang, Yu-Cai; Long, Hong-Yan; Xiong, Meng-Hua; Mao, Cheng-Qiong; Yao, Yan-Dan; Wang, Jun

2012-06-26

The clinical success of therapeutics of small interfering RNA (siRNA) is still hindered by its delivery systems. Cationic polymer or lipid-based vehicles as the major delivery systems of siRNA cannot sufficiently satisfy siRNA therapeutic applications. It is hypothesized that cationic lipid-polymer hybrid nanoparticles may take advantage of both polymeric and lipid-based nanoparticles for siRNA delivery, while diminishing the shortcomings of both. In this study, cationic lipid-polymer hybrid nanoparticles were prepared by a single-step nanoprecipitation of a cationic lipid (N,N-bis(2-hydroxyethyl)-N-methyl-N-(2-cholesteryloxycarbonyl aminoethyl) ammonium bromide, BHEM-Chol) and amphiphilic polymers for systemic delivery of siRNA. The formed hybrid nanoparticles comprised a hydrophobic polylactide core, a hydrophilic poly(ethylene glycol) shell, and a cationic lipid monolayer at the interface of the core and the shell. Such hybrid nanoparticles exhibited excellent stability in serum and showed significantly improved biocompatibility compared to that of pure BHEM-Chol particles. The hybrid nanoparticles were capable of delivering siRNA into BT474 cells and facilitated the escape of loaded siRNA from the endosome into the cytoplasm. The hybrid nanoparticles carrying polo-like kinase 1 (Plk1)-specific siRNA (siPlk1) remarkably and specifically downregulated expression of the oncogene Plk1 and induced cancer cell apoptosis both in vitro and in vivo and significantly suppressed tumor growth following systemic administration. We demonstrate that this system is stable, nontoxic, highly efficient, and easy to scale up, bringing the clinical application of siRNA therapy one important step closer to reality.

Implementation of a school-based social and emotional learning intervention: understanding diffusion processes within complex systems.

PubMed

Evans, Rhiannon; Murphy, Simon; Scourfield, Jonathan

2015-07-01

Sporadic and inconsistent implementation remains a significant challenge for social and emotional learning (SEL) interventions. This may be partly explained by the dearth of flexible, causative models that capture the multifarious determinants of implementation practices within complex systems. This paper draws upon Rogers (2003) Diffusion of Innovations Theory to explain the adoption, implementation and discontinuance of a SEL intervention. A pragmatic, formative process evaluation was conducted in alignment with phase 1 of the UK Medical Research Council's framework for Developing and Evaluating Complex Interventions. Employing case-study methodology, qualitative data were generated with four socio-economically and academically contrasting secondary schools in Wales implementing the Student Assistance Programme. Semi-structured interviews were conducted with 15 programme stakeholders. Data suggested that variation in implementation activity could be largely attributed to four key intervention reinvention points, which contributed to the transformation of the programme as it interacted with contextual features and individual needs. These reinvention points comprise the following: intervention training, which captures the process through which adopters acquire knowledge about a programme and delivery expertise; intervention assessment, which reflects adopters' evaluation of an intervention in relation to contextual needs; intervention clarification, which comprises the cascading of knowledge through an organisation in order to secure support in delivery; and intervention responsibility, which refers to the process of assigning accountability for sustainable delivery. Taken together, these points identify opportunities to predict and intervene with potential implementation problems. Further research would benefit from exploring additional reinvention activity.

Interlending and Document Delivery. IATUL Proceedings, Vol. 16.

ERIC Educational Resources Information Center

Fjallbrant, Nancy, Ed.

1984-01-01

This issue of the IATUL (International Association of Technological University Libraries) Proceedings provides an overview of interlending and document delivery in a number of countries. The document comprises: (1) "Interlibrary Lending in the United Kingdom" (Maurice B. Line); (2) "Interlending and Document Delivery in the Federal…

Nanochanneled Device and Related Methods

NASA Technical Reports Server (NTRS)

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

2013-01-01

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

Utilisation of maternal health care in western rural China under a new rural health insurance system (New Co-operative Medical System).

PubMed

Long, Qian; Zhang, Tuohong; Xu, Ling; Tang, Shenglan; Hemminki, Elina

2010-10-01

To investigate factors influencing maternal health care utilisation in western rural China and its relation to income before (2002) and after (2007) introducing a new rural health insurance system (NCMS). Data from cross-sectional household-based health surveys carried out in ten western rural provinces of China in 2003 and 2008 were used in the study. The study population comprised women giving birth in 2002 or 2007, with 917 and 809 births, respectively. Correlations between outcomes and explanatory variables were studied by logistic regression models and a log-linear model. Between 2002 and 2007, having no any pre-natal visit decreased from 25% to 12% (difference 13%, 95% CI 10-17%); facility-based delivery increased from 45% to 80% (difference 35%, 95% CI 29-37%); and differences in using pre-natal and delivery care between the income groups narrowed. In a logistic regression analysis, women with lower education, from minority groups, or high parity were less likely to use pre-natal and delivery care in 2007. The expenditure for facility-based delivery increased over the period, but the out-of-pocket expenditure for delivery as a percentage of the annual household income decreased. In 2007, it was 14% in the low-income group. NCMS participation was found positively correlated with lower out-of-pocket expenditure for facility-based delivery (coefficient -1.14 P < 0.05) in 2007. Facility-based delivery greatly increased between 2002 and 2007, coinciding with the introduction of the NCMS. The rural poor were still facing substantial payment for facility-based delivery, although NCMS participation reduced the out-of-pocket expenditure on average. © 2010 Blackwell Publishing Ltd.

Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo

PubMed Central

EL Andaloussi, Samir; Lehto, Taavi; Mäger, Imre; Rosenthal-Aizman, Katri; Oprea, Iulian I.; Simonson, Oscar E.; Sork, Helena; Ezzat, Kariem; Copolovici, Dana M.; Kurrikoff, Kaido; Viola, Joana R.; Zaghloul, Eman M.; Sillard, Rannar; Johansson, Henrik J.; Said Hassane, Fatouma; Guterstam, Peter; Suhorutšenko, Julia; Moreno, Pedro M. D.; Oskolkov, Nikita; Hälldin, Jonas; Tedebark, Ulf; Metspalu, Andres; Lebleu, Bernard; Lehtiö, Janne; Smith, C. I. Edvard; Langel, Ülo

2011-01-01

While small interfering RNAs (siRNAs) have been rapidly appreciated to silence genes, efficient and non-toxic vectors for primary cells and for systemic in vivo delivery are lacking. Several siRNA-delivery vehicles, including cell-penetrating peptides (CPPs), have been developed but their utility is often restricted by entrapment following endocytosis. Hence, developing CPPs that promote endosomal escape is a prerequisite for successful siRNA implementation. We here present a novel CPP, PepFect 6 (PF6), comprising the previously reported stearyl-TP10 peptide, having pH titratable trifluoromethylquinoline moieties covalently incorporated to facilitate endosomal release. Stable PF6/siRNA nanoparticles enter entire cell populations and rapidly promote endosomal escape, resulting in robust RNAi responses in various cell types (including primary cells), with minimal associated transcriptomic or proteomic changes. Furthermore, PF6-mediated delivery is independent of cell confluence and, in most cases, not significantly hampered by serum proteins. Finally, these nanoparticles promote strong RNAi responses in different organs following systemic delivery in mice without any associated toxicity. Strikingly, similar knockdown in liver is achieved by PF6/siRNA nanoparticles and siRNA injected by hydrodynamic infusion, a golden standard technique for liver transfection. These results imply that the peptide, in addition to having utility for RNAi screens in vitro, displays therapeutic potential. PMID:21245043

Radiant{trademark} Liquid Radioisotope Intravascular Radiation Therapy System

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

Eigler, N.; Whiting, J.; Chernomorsky, A.

1998-01-16

RADIANT{trademark} is manufactured by United States Surgical Corporation, Vascular Therapies Division, (formerly Progressive Angioplasty Systems). The system comprises a liquid {beta}-radiation source, a shielded isolation/transfer device (ISAT), modified over-the-wire or rapid exchange delivery balloons, and accessory kits. The liquid {beta}-source is Rhenium-188 in the form of sodium perrhenate (NaReO{sub 4}), Rhenium-188 is primarily a {beta}-emitter with a physical half-life of 17.0 hours. The maximum energy of the {beta}-particles is 2.1 MeV. The source is produced daily in the nuclear pharmacy hot lab by eluting a Tungsten-188/Rhenium-188 generator manufactured by Oak Ridge National Laboratory (ORNL). Using anion exchange columns and Milliporemore » filters the effluent is concentrated to approximately 100 mCi/ml, calibrated, and loaded into the (ISAT) which is subsequently transported to the cardiac catheterization laboratory. The delivery catheters are modified Champion{trademark} over-the-wire, and TNT{trademark} rapid exchange stent delivery balloons. These balloons have thickened polyethylene walls to augment puncture resistance; dual radio-opaque markers and specially configured connectors.« less

Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor.

PubMed

Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred; Micera, Silvestro

2009-04-01

The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.

Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin.

PubMed

Wu, Bo; Yu, Ping; Cui, Can; Wu, Ming; Zhang, Yang; Liu, Lei; Wang, Cai-Xia; Zhuo, Ren-Xi; Huang, Shi-Wen

2015-04-01

The development and evaluation of folate-targeted and reduction-triggered biodegradable nanoparticles are introduced to the research on targeted delivery of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA) core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16) reduction-sensitive shell, and a folic acid-targeted ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated cancer cell reductive environment. The experiments on the release process in vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from flow cytometry, confocal image and in vitro cytotoxicity assays revealed that FLPNPs further enhanced cell uptake and generated higher cytotoxicity against human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive and targeted redox-insensitive controls. Furthermore, in vivo animal experiments demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations have proved to be a stable, controllable and targeted anticancer drug delivery system.

Mucoadhesive Chitosan-Pectinate Nanoparticles for the Delivery of Curcumin to the Colon.

PubMed

Alkhader, Enas; Billa, Nashiru; Roberts, Clive J

2017-05-01

In the present study, we report the properties of a mucoadhesive chitosan-pectinate nanoparticulate formulation able to retain its integrity in the milieu of the upper gastrointestinal tract and subsequently, mucoadhere and release curcumin in colon conditions. Using this system, we aimed to deliver curcumin to the colon for the possible management of colorectal cancer. The delivery system comprised of a chitosan-pectinate composite nanopolymeric with a z-average of 206.0 nm (±6.6 nm) and zeta potential of +32.8 mV (±0.5 mV) and encapsulation efficiency of 64%. The nanoparticles mucoadhesiveness was higher at alkaline pH compared to acidic pH. Furthermore, more than 80% release of curcumin was achieved in pectinase-enriched medium (pH 6.4) as opposed to negligible release in acidic and enzyme-restricted media at pH 6.8. SEM images of the nanoparticles after exposure to the various media indicate a retained matrix in acid media as opposed to a distorted/fragmented matrix in pectinase-enriched medium. The data strongly indicates that the system has the potential to be applied as a colon-targeted mucoadhesive curcumin delivery system for the possible treatment of colon cancer.

Case study of a central-station grid-intertie photovoltaic system with V-trough concentration

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

Freilich, J.; Gordon, J.M.

1991-01-01

This presentation is a cast study of an installed, central-station (no storage), utility-intertie photovoltaic (PV) system in Sede Boqer, Israel (latitude 30.9{degree}N). The nominally 12 kW peak PV system is comprised of 189 polycrystalline silicon modules mounted on inexpensive, one-axis north-south horizontal trackers with V-trough mirrors for optical boost. The power conditioning unit operates at a fixed voltage rather than at maximum power point (MPP). The primary task in analyzing the installed system was to investigate the cause of measured power output significantly below the design predictions of the installers, and to recommend system design modifications. Subsequent tasks included themore » quantitative assessment of fixed-voltage operation and of the energetic value of V-trough concentration and one-axis tracking for this system. Sample results show: (1) fixed-voltage operation at the best fixed voltage (BFV) can achieve around 96% of the yearly energy of MPP operation; (2) the sensitivity of the yearly energy delivery to the selection of fixed voltage and its marked asymmetry about the BFV; (3) the influences of inverter current constraints on yearly energy delivery and BFV; and (4) how the separate effects of tracking and optical concentration increase yearly energy delivery.« less

Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

PubMed

Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

2016-01-01

The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

Nanoparticles in the ocular drug delivery

PubMed Central

Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

2013-01-01

Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

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

PubMed Central

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

2014-01-01

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

Star-shaped poly(oligoethylene glycol) copolymer-based gels: Thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery.

PubMed

Soliman, Mahmoud E; Elmowafy, Enas; Casettari, Luca; Alexander, Cameron

2018-05-30

The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides as Delivery Vectors.

PubMed

Kristensen, Mie; Brodin, Birger

2017-09-01

A number of potent drugs for the treatment of brain diseases are available. However, in order for them to reach their target site of action, they must pass the blood-brain barrier (BBB). The capillary endothelium comprises the major barrier of the BBB and allows only passive permeation of some small lipophilic molecules. Brain delivery of the larger biopharmaceuticals, which today includes an increasing number of novel drug entities, is therefore restricted, both due to their molecular size and their hydrophilic nature. Thus, the development of novel drug entities intended for the treatment of brain diseases such as neurodegenerative diseases or brain cancers require a delivery strategy for overcoming the BBB before reaching its final target within the brain. Peptide-based delivery vector is an emerging tool as shuttles for drug delivery across the BBB and one may explore receptor-mediated transcytosis, adsorptive-mediated transcytosis, and the paracellular route. The latter, however, being controversial due to the risk of co-delivery of blood-borne potential harmful substances. On the other hand, a number of studies report on drug delivery across the BBB exploiting receptor-mediated transcytosis and adsorptive-mediated transcytosis, indicating that peptides and peptide vectors may be of use in a central nervous system delivery context. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Emerging Roles for Extracellular Vesicles in Tissue Engineering and Regenerative Medicine

PubMed Central

Lamichhane, Tek N.; Sokic, Sonja; Schardt, John S.; Raiker, Rahul S.; Lin, Jennifer W.

2015-01-01

Extracellular vesicles (EVs)—comprising a heterogeneous population of cell-derived lipid vesicles including exosomes, microvesicles, and others—have recently emerged as both mediators of intercellular information transfer in numerous biological systems and vehicles for drug delivery. In both roles, EVs have immense potential to impact tissue engineering and regenerative medicine applications. For example, the therapeutic effects of several progenitor and stem cell-based therapies have been attributed primarily to EVs secreted by these cells, and EVs have been recently reported to play direct roles in injury-induced tissue regeneration processes in multiple physiological systems. In addition, EVs have been utilized for targeted drug delivery in regenerative applications and possess unique potential to be harnessed as patient-derived drug delivery vehicles for personalized medicine. This review discusses EVs in the context of tissue repair and regeneration, including their utilization as drug carriers and their crucial role in cell-based therapies. Furthermore, the article highlights the growing need for bioengineers to understand, consider, and ultimately design and specifically control the activity of EVs to maximize the efficacy of tissue engineering and regenerative therapies. PMID:24957510

Thiolated chitosan: development and in vivo evaluation of an oral delivery system for leuprolide.

PubMed

Iqbal, Javed; Shahnaz, Gul; Perera, Glen; Hintzen, Fabian; Sarti, Federica; Bernkop-Schnürch, Andreas

2012-01-01

The aim of the present study was to develop an oral delivery system for the peptide drug leuprolide. Gel formulations based on unmodified chitosan/reduced glutathione (GSH) and chitosan-thioglycolic acid (chitosan-TGA)/GSH were prepared, and their effect on the absorption of leuprolide was evaluated in vitro and in vivo in male Sprague Dawley rats. Transport studies were performed with freshly excised rat intestinal mucosa mounted in Ussing-type chambers. Due to the addition of gel formulations comprising 0.5% (m/v) unmodified chitosan/0.5% (m/v) GSH and 0.5% (m/v) chitosan-TGA/0.5% (m/v) GSH, the transport of leuprolide across excised mucosa was improved up to 2.06-fold and 3.79-fold, respectively, in comparison with leuprolide applied in buffer (P(app)=2.87 ± 0.77 × 10⁻⁶ cm/s). In vivo, the addition of oral gel formulation comprising 8 mg of unmodified chitosan, 1mg of GSH and 1mg of leuprolide increased the area under the plasma concentration-time curve (AUC₀₋₈) of leuprolide 1.39-fold in comparison with leuprolide having been administered just in saline. Moreover, the administration of oral gel formulation comprising 8 mg of chitosan-TGA, 1mg of GSH and 1mg of leuprolide resulted in a further enhanced leuprolide plasma concentration, and the area under the plasma concentration-time curve (AUC₀₋₈) of leuprolide was increased 3.72-fold in comparison with the control. With the oral gel formulation comprising 8 mg of chitosan-TGA, a relative bioavailability (versus s.c. injection) of 4.5% was achieved in contrast to the control displaying a relative bioavailability of 1.2%. Thus, according to the achieved results, it is suggested that chitosan-TGA in combination with GSH is a valuable tool for improving the oral bioavailability of the peptide drug leuprolide. Copyright © 2011 Elsevier B.V. All rights reserved.

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin.

PubMed

Chen, Wei-Liang; Li, Fang; Tang, Yan; Yang, Shu-di; Li, Ji-Zhao; Yuan, Zhi-Qiang; Liu, Yang; Zhou, Xiao-Feng; Liu, Chun; Zhang, Xue-Nong

2017-01-01

Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents.

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin

PubMed Central

Chen, Wei-liang; Li, Fang; Tang, Yan; Yang, Shu-di; Li, Ji-zhao; Yuan, Zhi-qiang; Liu, Yang; Zhou, Xiao-feng; Liu, Chun; Zhang, Xue-nong

2017-01-01

Physicochemical properties, including particle size, zeta potential, and drug release behavior, affect targeting efficiency, cellular uptake, and antitumor effect of nanocarriers in a formulated drug-delivery system. In this study, a novel stepwise pH-responsive nanodrug delivery system was developed to efficiently deliver and significantly promote the therapeutic effect of doxorubicin (DOX). The system comprised dimethylmaleic acid-chitosan-urocanic acid and elicited stepwise responses to extracellular and intracellular pH. The nanoparticles (NPs), which possessed negative surface charge under physiological conditions and an appropriate nanosize, exhibited advantageous stability during blood circulation and enhanced accumulation in tumor sites via enhanced permeability and retention effect. The tumor cellular uptake of DOX-loaded NPs was significantly promoted by the first-step pH response, wherein surface charge reversion of NPs from negative to positive was triggered by the slightly acidic tumor extracellular environment. After internalization into tumor cells, the second-step pH response in endo/lysosome acidic environment elicited the on-demand intracellular release of DOX from NPs, thereby increasing cytotoxicity against tumor cells. Furthermore, stepwise pH-responsive NPs showed enhanced antiproliferation effect and reduced systemic side effect in vivo. Hence, the stepwise pH-responsive NPs provide a promising strategy for efficient delivery of antitumor agents. PMID:28652730

Synthetic LDL as targeted drug delivery vehicle

DOEpatents

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

2012-08-28

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

Capillary photoelectrode structures for photoelectrochemical and photocatalytic cells

DOEpatents

Wang, Xudong; Li, Zhaodong; Cai, Zhiyong; Yao, Chunhua

2017-05-02

Photocatalytic structures having a capillary-force based electrolyte delivery system are provided. Also provided are photoelectrochemical and photocatalytic cells incorporating the structures and methods for using the cells to generate hydrogen and/or oxygen from water. The photocatalytic structures use an electrolyte-transporting strip comprising a porous network of cellulose nanofibers to transport electrolyte from a body of the electrolyte to a porous photoelectrode or a porous photocatalytic substrate via capillary force.

New responsibilities in purchasing and developing services.

PubMed

Jerram, Soline; Fox, Ann

2014-06-01

The role of nursing in the NHS commissioning structure in England is developing. Since April 2013 more than 200 clinical commissioning groups (CCGs), which comprise all GP practices in the locality, have taken on responsibility for health budgets in their areas. This article describes the challenges ahead and nurses' responsibilities in CCGs when working with local citizens and across the health and social care system to assure the delivery of high quality, safe services.

Design of a transdermal delivery system for aspirin as an antithrombotic drug.

PubMed

Ammar, H O; Ghorab, M; El-Nahhas, S A; Kamel, R

2006-12-11

Aspirin has become the gold standard to which newer antiplatelet drugs are compared for reducing risks of cardiovascular diseases, while keeping low cost. Oral aspirin has a repertoire of gastrointestinal side effects even at low doses and requires high frequent dosing because it undergoes extensive presystemic metabolism. Transdermal delivery offers an alternative route that bypasses the gut and may be more convenient and safer for aspirin delivery especially during long-term use. This study comprised formulation of aspirin in different topical bases. Release studies revealed that hydrocarbon gel allowed highest drug release. In vitro permeation studies revealed high drug permeation from hydrocarbon gel. Several chemical penetration enhancers were monitored for augmenting the permeation from this base. Combination of propylene glycol and alcohol showed maximum enhancing effect and, hence, was selected for biological investigation. The biological performance of the selected formulation was assessed by measuring the inhibition of platelet aggregation relevant to different dosage regimens aiming to minimize both drug dose and frequency of application. The results demonstrated the feasibility of successfully influencing platelet function and revealed that the drug therapeutic efficacy in transdermal delivery system is dose independent. Biological performance was re-assessed after storage and the results revealed stability and persistent therapeutic efficacy.

The state of medical informatics in India: a roadmap for optimal organization.

PubMed

Sarbadhikari, Suptendra Nath

2005-04-01

In India, the healthcare delivery systems are based on manual record keeping despite a good telecommunication infrastructure. Unfortunately, Indian policy makers are yet to realize the importance of medical informatics (including tele-health, which comprises e-Health and Telemedicine) in delivering healthcare. In the medical curriculum also, nowhere is this treated as a subject or even as a tool for learning. The final aim of most of the medical and paramedical students should be to become good users, and if possible, also experts for advancing medical knowledge base through medical informatics. In view of the fast changing world of medical informatics, it is essential to formulate a flexible syllabus rather than a rigid one for incorporating into the regular curriculum of medical and paramedical education. Only after that one may expect all members of the healthcare delivery systems to adopt and apply medical informatics optimally as a routine tool for their services.

S-protected thiolated chitosan: Synthesis and in vitro characterization

PubMed Central

Dünnhaupt, Sarah; Barthelmes, Jan; Thurner, Clemens C.; Waldner, Claudia; Sakloetsakun, Duangkamon; Bernkop-Schnürch, Andreas

2012-01-01

Purpose of the present study was the generation and evaluation of novel thiolated chitosans, so-named S-protected thiolated chitosans as mucosal drug delivery systems. Stability of all conjugates concerning swelling and disintegration behavior as well as drug release was examined. Mucoadhesive properties were evaluated in vitro on intestinal mucosa. Different thiolated chitosans were generated displaying increasing amounts of attached free thiol groups on the polymer, whereby more than 50% of these thiol groups were linked with 6-mercaptonicotinamide. Based on the implementation of this hydrophobic residue, the swelling behavior was 2-fold decreased, whereas stability was essentially improved. Their mucoadhesive properties were 2- and 14-fold increased compared to corresponding thiolated and unmodified chitosans, respectively. Release studies out of matrix tablets comprising the novel conjugates revealed a controlled release of a model peptide. Accordingly, S-protected thiomers represent a promising type of mucoadhesive polymers for the development of various mucosal drug delivery systems. PMID:22839999

Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

NASA Astrophysics Data System (ADS)

Hong, Sung-Ha; Szili, Endre J.; Jenkins, A. Toby A.; Short, Robert D.

2014-09-01

This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine.

Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review

PubMed Central

Liu, Jie; Gray, Warren D.; Davis, Michael E.; Luo, Ying

2012-01-01

Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell- and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure–function relationship of ligand–dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. PMID:23741608

Electrostatically assembled dendrimer complex with a high-affinity protein binder for targeted gene delivery.

PubMed

Kim, Jong-Won; Lee, Joong-Jae; Choi, Joon Sig; Kim, Hak-Sung

2018-06-10

Although a variety of non-viral gene delivery systems have been developed, they still suffer from low efficiency and specificity. Herein, we present the assembly of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new format for targeted gene delivery. A PAMAM dendrimer modified with histidine and arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection efficiency. An EGFR-specific repebody, composed of leucine-rich repeat (LRR) modules, was employed as a targeting moiety. A polyanionic peptide was genetically fused to the repebody, followed by incubation with an HR-dendrimer and a DNA cargo to assemble the dendrimer complex through an electrostatic interaction. The resulting dendrimer complex was shown to deliver a DNA cargo with high efficiency in a receptor-specific manner. An analysis using a confocal microscope confirmed the internalization of the dendrimer complex and subsequent dissociation of a DNA cargo from the complex. The present approach can be broadly used in a targeted gene delivery in many areas. Copyright © 2018 Elsevier B.V. All rights reserved.

Insulin Patch Pumps: Their Development and Future in Closed-Loop Systems

PubMed Central

Bohannon, Nancy J.V.

2010-01-01

Abstract Steady progress is being made toward the development of a so-called “artificial pancreas,” which may ultimately be a fully automated, closed-loop, glucose control system comprising a continuous glucose monitor, an insulin pump, and a controller. The controller will use individualized algorithms to direct delivery of insulin without user input. A major factor propelling artificial pancreas development is the substantial incidence of—and attendant patient, parental, and physician concerns about—hypoglycemia and extreme hyperglycemia associated with current means of insulin delivery for type 1 diabetes mellitus (T1DM). A successful fully automated artificial pancreas would likely reduce the frequency of and anxiety about hypoglycemia and marked hyperglycemia. Patch-pump systems (“patch pumps”) are likely to be used increasingly in the control of T1DM and may be incorporated into the artificial pancreas systems of tomorrow. Patch pumps are free of tubing, small, lightweight, and unobtrusive. This article describes features of patch pumps that have been approved for U.S. marketing or are under development. Included in the review is an introduction to control algorithms driving insulin delivery, particularly the two major types: proportional integrative derivative and model predictive control. The use of advanced algorithms in the clinical development of closed-loop systems is reviewed along with projected next steps in artificial pancreas development. PMID:20515308

An overview of the NASA electronic components information management system

NASA Technical Reports Server (NTRS)

Kramer, G.; Waterbury, S.

1991-01-01

The NASA Parts Project Office (NPPO) comprehensive data system to support all NASA Electric, Electronic, and Electromechanical (EEE) parts management and technical data requirements is described. A phase delivery approach is adopted, comprising four principal phases. Phases 1 and 2 support Space Station Freedom (SSF) and use a centralized architecture with all data and processing kept on a mainframe computer. Phases 3 and 4 support all NASA centers and projects and implement a distributed system architecture, in which data and processing are shared among networked database servers. The Phase 1 system, which became operational in February of 1990, implements a core set of functions. Phase 2, scheduled for release in 1991, adds functions to the Phase 1 system. Phase 3, to be prototyped beginning in 1991 and delivered in 1992, introduces a distributed system, separate from the Phase 1 and 2 system, with a refined semantic data model. Phase 4 extends the data model and functionality of the Phase 3 system to provide support for the NASA design community, including integration with Computer Aided Design (CAD) environments. Phase 4 is scheduled for prototyping in 1992 to 93 and delivery in 1994.

Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy.

PubMed

Oh, Keun Sang; Kim, Kyungim; Yoon, Byeong Deok; Lee, Hye Jin; Park, Dal Yong; Kim, Eun-Yeong; Lee, Kiho; Seo, Jae Hong; Yuk, Soon Hong

2016-01-01

A mixture of docetaxel (DTX) and Solutol(®) HS 15 (Solutol) transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs) with a DTX-loaded Solutol nanodroplet (as template NPs) core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm) were observed to have an increased average diameter (from 11.7 nm to 156.1 nm) and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects.

Design and preliminary accuracy studies of an MRI-guided transrectal prostate intervention system.

PubMed

Krieger, Axel; Csoma, Csaba; Iordachital, Iulian I; Guion, Peter; Singh, Anurag K; Fichtinger, Gabor; Whitcomb, Louis L

2007-01-01

This paper reports a novel system for magnetic resonance imaging (MRI) guided transrectal prostate interventions, such as needle biopsy, fiducial marker placement, and therapy delivery. The system utilizes a hybrid tracking method, comprised of passive fiducial tracking for initial registration and subsequent incremental motion measurement along the degrees of freedom using fiber-optical encoders and mechanical scales. Targeting accuracy of the system is evaluated in prostate phantom experiments. Achieved targeting accuracy and procedure times were found to compare favorably with existing systems using passive and active tracking methods. Moreover, the portable design of the system using only standard MRI image sequences and minimal custom scanner interfacing allows the system to be easily used on different MRI scanners.

Near-Infrared Imaging Method for the In Vivo Assessment of the Biodistribution of Nanoporous Silicon Particles

PubMed Central

Tasciotti, Ennio; Godin, Biana; Martinez, Jonathan O.; Chiappini, Ciro; Bhavane, Rohan; Liu, Xuewu; Ferrari, Mauro

2011-01-01

In the development of new nanoparticle-based technologies for therapeutic and diagnostic purposes, understanding the fate of nanoparticles in the body is crucial. We recently developed a multistage vector delivery system comprising biodegradable and biocompatible nanoporous silicon particles (first-stage microparticles [S1MPs]) able to host, protect, and deliver second-stage therapeutic and diagnostic nanoparticles (S2NPs) on intravenous injection. This delivery system aims at sequentially overcoming the biologic barriers en route to the target delivery site by separating and assigning tasks to the coordinated logic-embedded vectors constituting it. In this work, by conjugating a near-infrared dye on the surface of the S1MP without compromising the porous structure and potential loading of S2NPs, we were able to monitor the in vivo distribution of S1MPs in healthy mice using an optical imaging system. It was observed that particles predominantly accumulated in the liver and spleen at the end of 24 hours. Further quantification of S1MPs in the major organs of the animals by elemental analysis of silicon using inductively coupled plasma-atomic electron spectroscopy verified the accuracy of in vivo near-infrared imaging as a tool for evaluation of nanovector biodistribution. PMID:21303615

Pharmacologic Effects in vivo in Brain by Vector-Mediated Peptide Drug Delivery

NASA Astrophysics Data System (ADS)

Bickel, Ulrich; Yoshikawa, Takayoshi; Landaw, Elliot M.; Faull, Kym F.; Pardridge, William M.

1993-04-01

Pharmacologic effects in brain caused by systemic administration of neuropeptides are prevented by poor transport of the peptide through the brain vascular endothelium, which comprises the blood-brain barrier in vivo. In the present study, successful application of a chimeric peptide approach to enhance drug delivery through the blood-brain barrier for the purpose of achieving a central nervous system pharmacologic effect is described. The chimeric peptide was formed by linkage of a potent vasoactive intestinal peptide (VIP) analogue, which had been monobiotinylated, to a drug transport vector. The vector consisted of a covalent conjugate of avidin and the OX26 monoclonal antibody to the transferrin receptor. Owing to the high concentration of transferrin receptors on brain capillary endothelia, OX26 targets brain and undergoes receptor-mediated transcytosis through the blood-brain barrier. Systemic infusion of low doses (12 μg/kg) of the VIP chimeric peptide in rats resulted in an in vivo central nervous system pharmacologic effect: a 65% increase in cerebral blood flow. Biotinylated VIP analogue without the brain transport vector was ineffective.

Laser beam alignment and profilometry using diagnostic fluorescent safety mirrors

NASA Astrophysics Data System (ADS)

Lizotte, Todd E.

2011-03-01

There are a wide range of laser beam delivery systems in use for various purposes; including industrial and medical applications. Virtually all such beam delivery systems for practical purposes employ optical systems comprised of mirrors and lenses to shape, focus and guide the laser beam down to the material being processed. The goal of the laser beam delivery is to set the optimum parameters and to "fold" the beam path to reduce the mechanical length of the optical system, thereby allowing a physically compact system. In many cases, even a compact system can incorporate upwards of six mirrors and a comparable number of lenses all needing alignment so they are collinear. One of the major requirements for use of such systems in industry is a method of safe alignment. The alignment process requires that the aligner determine where the beam strikes each element. The aligner should also preferably be able to determine the shape or pattern of the laser beam at that point and its relative power. These alignments are further compounded in that the laser beams generated are not visible to the unaided human eye. Such beams are also often of relatively high power levels, and are thereby a significant hazard to the eyes of the aligner. Obvious an invisible beam makes it nearly impossible to align laser system without some form of optical assistance. The predominant method of visually aligning the laser beam delivery is the use of thermal paper, paper cards or fluorescing card material. The use of paper products which have limited power handling capability or coated plastics can produce significant debris and contaminants within the beam line that ultimately damage the optics. The use of the cards can also create significant laser light scatter jeopardizing the safety of the person aligning the system. This paper covers a new safety mirror design for use with at various UV and Near IR wavelengths (193 nm to 1064 nm) within laser beam delivery systems and how its use can provide benefits covering eye safety, precise alignment and beam diagnostics.

Self-assembled lipid bilayer materials

DOEpatents

Sasaki, Darryl Y.; Waggoner, Tina A.; Last, Julie A.

2005-11-08

The present invention is a self-assembling material comprised of stacks of lipid bilayers formed in a columnar structure, where the assembly process is mediated and regulated by chemical recognition events. The material, through the chemical recognition interactions, has a self-regulating system that corrects the radial size of the assembly creating a uniform diameter throughout most of the structure. The materials form and are stable in aqueous solution. These materials are useful as structural elements for the architecture of materials and components in nanotechnology, efficient light harvesting systems for optical sensing, chemical processing centers, and drug delivery vehicles.

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

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

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

Three-dimensional illumination procedure for photodynamic therapy of dermatology

NASA Astrophysics Data System (ADS)

Hu, Xiao-ming; Zhang, Feng-juan; Dong, Fei; Zhou, Ya

2014-09-01

Light dosimetry is an important parameter that affects the efficacy of photodynamic therapy (PDT). However, the irregular morphologies of lesions complicate lesion segmentation and light irradiance adjustment. Therefore, this study developed an illumination demo system comprising a camera, a digital projector, and a computing unit to solve these problems. A three-dimensional model of a lesion was reconstructed using the developed system. Hierarchical segmentation was achieved with the superpixel algorithm. The expected light dosimetry on the targeted lesion was achieved with the proposed illumination procedure. Accurate control and optimization of light delivery can improve the efficacy of PDT.

PILOT: An intelligent distributed operations support system

NASA Technical Reports Server (NTRS)

Rasmussen, Arthur N.

1993-01-01

The Real-Time Data System (RTDS) project is exploring the application of advanced technologies to the real-time flight operations environment of the Mission Control Centers at NASA's Johnson Space Center. The system, based on a network of engineering workstations, provides services such as delivery of real time telemetry data to flight control applications. To automate the operation of this complex distributed environment, a facility called PILOT (Process Integrity Level and Operation Tracker) is being developed. PILOT comprises a set of distributed agents cooperating with a rule-based expert system; together they monitor process operation and data flows throughout the RTDS network. The goal of PILOT is to provide unattended management and automated operation under user control.

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

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

Schempf, H.; Bares, J.E.

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

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

PubMed

Ghai, Damanjeet; Sinha, Vivek Ranjan

2012-07-01

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

Blood brain barrier: a challenge for effectual therapy of brain tumors.

PubMed

Bhowmik, Arijit; Khan, Rajni; Ghosh, Mrinal Kanti

2015-01-01

Brain tumors are one of the most formidable diseases of mankind. They have only a fair to poor prognosis and high relapse rate. One of the major causes of extreme difficulty in brain tumor treatment is the presence of blood brain barrier (BBB). BBB comprises different molecular components and transport systems, which in turn create efflux machinery or hindrance for the entry of several drugs in brain. Thus, along with the conventional techniques, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle for treatment of brain tumors. In this review, we have elucidated some critical insights into the composition and function of BBB and along with it we have discussed the effective methods for delivery of drugs to the brain and therapeutic strategies overcoming the barrier.

Transportation systems analyses. Volume 2: Technical/programmatics

NASA Astrophysics Data System (ADS)

1993-05-01

The principal objective of this study is to accomplish a systems engineering assessment of the nation's space transportation infrastructure. This analysis addresses the necessary elements to perform man delivery and return, cargo transfer, cargo delivery, payload servicing, and the exploration of the Moon and Mars. Specific elements analyzed, but not limited to, include the Space Exploration Initiative (SEI), the National Launch System (NLS), the current expendable launch vehicle (ELV) fleet, ground facilities, the Space Station Freedom (SSF), and other civil, military and commercial payloads. The performance of this study entails maintaining a broad perspective on the large number of transportation elements that could potentially comprise the U.S. space infrastructure over the next several decades. To perform this systems evaluation, top-level trade studies are conducted to enhance our understanding of the relationships between elements of the infrastructure. This broad 'infrastructure-level perspective' permits the identification of preferred infrastructures. Sensitivity analyses are performed to assure the credibility and usefulness of study results. This report documents the three principal transportation systems analyses (TSA) efforts during the period 7 November 92 - 6 May 93. The analyses are as follows: Mixed-Fleet (STS/ELV) strategies for SSF resupply; Transportation Systems Data Book - overview; and Operations Cost Model - overview/introduction.

A nano particle vector comprised of poly lactic-co-glycolic acid and monophosphoryl lipid A and recombinant Mycobacterium avium subsp paratuberculosis peptides stimulate a pro-immune profile in bovine macrophages.

PubMed

Souza, Cleverson D; Bannantine, John P; Brown, Wendy C; Norton, M Grant; Davis, William C; Hwang, Julianne K; Ziaei, Parissa; Abdellrazeq, Gaber S; Eren, Meaghan V; Deringer, James R; Laws, Elizabeth; Cardieri, Maria Clara D

2017-05-14

We evaluated the potential of a nanoparticle (NP) delivery system to improve methods of delivery of candidate peptide-based vaccines for Paratuberculosis in cattle. Peptides derived from Mycobacterium avium subsp. paratuberculosis (Map), and the pro-inflammatory monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly (d,l-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with macrophages to examine their effects on survival and function. PLGA/MPLA NPs, with and without Map antigens, are efficiently phagocytized by macrophages with no evidence of toxicity. PLGA/MPLA NP formulations did not alter the level of expression of MHC I or II molecules. Expression of TNFα and IL12p40 was increased in Map-loaded NPs. T-cell proliferation studies using a model peptide from Anaplasma marginale demonstrated that a CD4 T-cell recall response could be elicited with macrophages pulsed with the peptide encapsulated in the PLGA/MPLA NP. These findings indicate PLGA/MPLA NPs can be used as a vehicle for delivery and testing of candidate peptide-based vaccines. These results will assist on more in depth studies on PLGA NP delivery systems that may lead to the development of a peptide-based vaccine for cattle. © 2017 The Society for Applied Microbiology.

Exosomes as Drug Delivery Vehicles for Parkinson’s Disease Therapy

PubMed Central

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

2015-01-01

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

Financial Management and Relationship Skills Education: Gauging Consumer Interest and Delivery Preferences

ERIC Educational Resources Information Center

Futris, Ted G.; Nielsen, Robert B.; Barton, Allen W.

2011-01-01

The study reported here explored level of interest and preferred delivery method of Extension programming related to financial management and relationship skills education. These two subjects comprise areas of Extension that often receive less recognition but appear as pertinent issues in the lives of many individuals. Using a diverse sample of…

Socio-demographic determinants of skilled birth attendant at delivery in rural southern Ghana.

PubMed

Manyeh, Alfred Kwesi; Akpakli, David Etsey; Kukula, Vida; Ekey, Rosemond Akepene; Narh-Bana, Solomon; Adjei, Alexander; Gyapong, Margaret

2017-07-11

Maternal mortality is the subject of the United Nations' fifth Millennium Development Goal, which is to reduce the maternal mortality ratio by three quarters from 1990 to 2015. The giant strides made by western countries in dropping of their maternal mortality ratio were due to the recognition given to skilled attendants at delivery. In Ghana, nine in ten mothers receive antenatal care from a health professional whereas only 59 and 68% of deliveries are assisted by skilled personnel in 2008 and 2010 respectively. This study therefore examines the determinants of skilled birth attendant at delivery in rural southern Ghana. This study comprises of 1874 women of reproductive age who had given birth 2 years prior to the study whose information were extracted from the Dodowa Health and Demographic Surveillance System. The univariable and multivariable associations between exposure variables (risk factors) and skilled birth attendant at delivery were explored using logistic regression. Out of a total of 1874 study participants, 98.29% of them receive antenatal care services during pregnancy and only 68.89% were assisted by skilled person at their last delivery prior to the survey. The result shows a remarkable influence of maternal age, level of education, parity, socioeconomic status and antenatal care attendance on skilled attendants at delivery. Although 69% of women in the study had skilled birth attendants at delivery, women from poorest households, higher parity, uneducated, and not attending antenatal care and younger women were more likely to deliver without a skilled birth attendants at delivery. Future intervention in the study area to bridge the gap between the poor and least poor women, improve maternal health and promote the use of skilled birth at delivery is recommended.

LOADING MACHINE FOR REACTORS

DOEpatents

Simon, S.L.

1959-07-01

An apparatus is described for loading or charging slugs of fissionable material into a nuclear reactor. The apparatus of the invention is a "muzzle loading" type comprising a delivery tube or muzzle designed to be brought into alignment with any one of a plurality of fuel channels. The delivery tube is located within the pressure shell and it is also disposed within shielding barriers while the fuel cantridges or slugs are forced through the delivery tube by an externally driven flexible ram.

Development and in vivo evaluation of an oral delivery system for low molecular weight heparin based on thiolated polycarbophil.

PubMed

Kast, Constantia E; Guggi, Davide; Langoth, Nina; Bernkop-Schnürch, Andreas

2003-06-01

It was the purpose of this study to develop a new oral drug delivery system for low molecular weight heparin (LMWH) providing an improved bioavailability and a prolonged therapeutic effect. The permeation enhancing polycarbophil-cysteine conjugate (PCP-Cys) used in this study displayed 111.4 +/- 6.4 microM thiol groups per gram polymer. Permeation studies on freshly excised intestinal mucosa were performed in Ussing chambers demonstrating a 2-fold improved uptake of heparin as a result of the addition of 0.5% (w/v) PCP-Cys and the permeation mediator glutathione (GSH). Tablets containing PCP-Cys, GSH, and 279 IU of LMWH showed a sustained drug release over 4 h. To guarantee the swelling of the polymeric carrier matrix in the small intestine tablets were enteric coated. They were orally given to rats. For tablets being based on the thiomer/GSH system an absolute bioavailability of 19.9 +/- 9.3% (means +/- SD; n = 5) vs. intravenous injection could be achieved. whereas tablets comprising unmodified PCP did not lead to a significant (p < 0.01) heparin concentration in plasma. The permeation enhancing effect and subsequently a therapeutic heparin level was maintained for 24 h after a single dose. Because of the strong and prolonged lasting permeation enhancing effect of the thiomer/GSH system, the oral bioavailability of LMWH could be significantly improved. This new delivery system represents therefore a promising tool for the oral administration of heparin.

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. Copyright © 2016. Published by Elsevier B.V.

S-protected thiolated chitosan: synthesis and in vitro characterization.

PubMed

Dünnhaupt, Sarah; Barthelmes, Jan; Thurner, Clemens C; Waldner, Claudia; Sakloetsakun, Duangkamon; Bernkop-Schnürch, Andreas

2012-10-01

Purpose of the present study was the generation and evaluation of novel thiolated chitosans, so-named S-protected thiolated chitosans as mucosal drug delivery systems. Stability of all conjugates concerning swelling and disintegration behavior as well as drug release was examined. Mucoadhesive properties were evaluated in vitro on intestinal mucosa. Different thiolated chitosans were generated displaying increasing amounts of attached free thiol groups on the polymer, whereby more than 50% of these thiol groups were linked with 6-mercaptonicotinamide. Based on the implementation of this hydrophobic residue, the swelling behavior was 2-fold decreased, whereas stability was essentially improved. Their mucoadhesive properties were 2- and 14-fold increased compared to corresponding thiolated and unmodified chitosans, respectively. Release studies out of matrix tablets comprising the novel conjugates revealed a controlled release of a model peptide. Accordingly, S-protected thiomers represent a promising type of mucoadhesive polymers for the development of various mucosal drug delivery systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer.

PubMed

Park, Jeenah; Thomas, Scott; Zhong, Allison Y; Wolfe, Alan R; Krings, Gregor; Terranova-Barberio, Manuela; Pawlowska, Nela; Benet, Leslie Z; Munster, Pamela N

2018-01-08

Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.

Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics.

PubMed

Maier, Martin A; Jayaraman, Muthusamy; Matsuda, Shigeo; Liu, Ju; Barros, Scott; Querbes, William; Tam, Ying K; Ansell, Steven M; Kumar, Varun; Qin, June; Zhang, Xuemei; Wang, Qianfan; Panesar, Sue; Hutabarat, Renta; Carioto, Mary; Hettinger, Julia; Kandasamy, Pachamuthu; Butler, David; Rajeev, Kallanthottathil G; Pang, Bo; Charisse, Klaus; Fitzgerald, Kevin; Mui, Barbara L; Du, Xinyao; Cullis, Pieter; Madden, Thomas D; Hope, Michael J; Manoharan, Muthiah; Akinc, Akin

2013-08-01

In recent years, RNA interference (RNAi) therapeutics, most notably with lipid nanoparticle-based delivery systems, have advanced into human clinical trials. The results from these early clinical trials suggest that lipid nanoparticles (LNPs), and the novel ionizable lipids that comprise them, will be important materials in this emerging field of medicine. A persistent theme in the use of materials for biomedical applications has been the incorporation of biodegradability as a means to improve biocompatibility and/or to facilitate elimination. Therefore, the aim of this work was to further advance the LNP platform through the development of novel, next-generation lipids that combine the excellent potency of the most advanced lipids currently available with biodegradable functionality. As a representative example of this novel class of biodegradable lipids, the lipid evaluated in this work displays rapid elimination from plasma and tissues, substantially improved tolerability in preclinical studies, while maintaining in vivo potency on par with that of the most advanced lipids currently available.

[Social medicine and dental health].

PubMed

Grünfeld, B

1976-03-01

Some socio-medical aspects of preventive and curative dental care. Preventive and early curative dental care is considered as an integral part of general health behavior in the individual. Different variables possibly determining such behavior are discussed. Demographic factors as age, sex, place of residence, as well as family and educational background, income and vocation seem to be of importance. A dental health delivery system free of charge to everyone in the age group 6-18, eventually up to 21 years has been available for several years in Norway. We assume that this has had a great impact upon the motivations for a positive atitude towards preventive care, particularly since economic barriers have been reduced simultaneously with shift in the popular value aspects of having good dental health status. Plans for a future incorporation of dental care into a total national health service, comprising the entire population, in order to make the delivery system feasible for everyone, will probably stimulate a still wider interest and motivation for preventive and early dental care.

Evaluation of critical formulation parameters in design and differentiation of self-microemulsifying drug delivery systems (SMEDDSs) for oral delivery of aciclovir.

PubMed

Janković, Jovana; Djekic, Ljiljana; Dobričić, Vladimir; Primorac, Marija

2016-01-30

The study investigated the influence of formulation parameters for design of self-microemulsifying drug delivery systems (SMEDDSs) comprising oil (medium chain triglycerides) (10%), surfactant (Labrasol(®), polysorbate 20, or Kolliphor(®) RH40), cosurfactant (Plurol(®) Oleique CC 497) (q.s. ad 100%), and cosolvent (glycerol or macrogol 400) (20% or 30%), and evaluate their potential as carriers for oral delivery of a poorly permeable antivirotic aciclovir (acyclovir). The drug loading capacity of the prepared formulations ranged from 0.18-31.66 mg/ml. Among a total of 60 formulations, three formulations meet the limits for average droplet size (Z-ave) and polydispersity index (PdI) that have been set for SMEDDSs (Z-ave≤100nm, PdI<0.250) upon spontaneous dispersion in 0.1M HCl and phosphate buffer pH 7.2. SMEDDSs with the highest aciclovir loading capacity (24.06 mg/ml and 21.12 mg/ml) provided the in vitro drug release rates of 0.325 mg cm(-2)min(-1) and 0.323 mg cm(-2)min(-1), respectively, and significantly enhanced drug permeability in the parallel artificial membrane permeability assay (PAMPA), in comparison with the pure drug substance. The results revealed that development of SMEDDSs with enhanced drug loading capacity and oral delivery potential, required optimization of hydrophilic ingredients, in terms of size of hydrophilic moiety of the surfactant, surfactant-to-cosurfactant mass ratio (Km), and log P of the cosolvent. Copyright © 2015 Elsevier B.V. All rights reserved.

Acoustic manipulation: Bessel beams and active carriers

NASA Astrophysics Data System (ADS)

Rajabi, Majid; Mojahed, Alireza

2017-10-01

In this paper, we address the interaction of zero-order acoustic Bessel beams as an acoustic manipulation tool, with an active spherical shell, as a carrier in drug, agent, or material delivery systems, in order to investigate the controllability of exerted acoustic radiation force as the driver. The active body is comprised of a spherical elastic shell stimulated in its monopole mode of vibrations with the same frequency as the incident wave field via an internally bonded and spatially uniformly excited piezoelectric actuator. The main aim of this work is to examine the performance of a nondiffracting and self-reconstructing zero-order Bessel beam to obtain the full manipulability condition of active carriers in comparison with the case of a plane wave field. The results unveil some unique potentials of the Bessel beams in the company of active carriers, with emphasis on the consumed power of the actuation system. This paper will widen the path toward the single-beam robust acoustic manipulation techniques and may lead to the prospect of combined tweezers and fields, with applications in delivery systems, microswimmers, and trapper designs.

Fuel injector

DOEpatents

Lambeth, Malcolm David Dick [Bromley, GB

2001-02-27

A fuel injector comprises first and second housing parts, the first housing part being located within a bore or recess formed in the second housing part, the housing parts defining therebetween an inlet chamber, a delivery chamber axially spaced from the inlet chamber, and a filtration flow path interconnecting the inlet and delivery chambers to remove particulate contaminants from the flow of fuel therebetween.

Nebuliser systems for drug delivery in cystic fibrosis.

PubMed

Daniels, Tracey; Mills, Nicola; Whitaker, Paul

2013-04-30

Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures. Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use.

Id-1 and Id-2 genes and products as therapeutic targets for treatment of breast cancer and other types of carcinoma

DOEpatents

Desprez, Pierre-Yves; Campisi, Judith

2014-09-30

A method for treatment and amelioration of breast, cervical, ovarian, endometrial, squamous cells, prostate cancer and melanoma in a patient comprising targeting Id-1 or Id-2 gene expression with a delivery vehicle comprising a product which modulates Id-1 or Id-2 expression.

Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides.

PubMed

Holm, René; Porter, Christopher J H; Edwards, Glenn A; Müllertz, Anette; Kristensen, Henning G; Charman, William N

2003-09-01

The potential for lipidic self-microemulsifying drug delivery systems (SMEDDS) containing triglycerides with a defined structure, where the different fatty acids on the glycerol backbone exhibit different metabolic fate, to improve the lymphatic transport and the portal absorption of a poorly water-soluble drug, halofantrine, were investigated in fasted lymph cannulated canines. Two different structured triglycerides were incorporated into the SMEDDS; 1,3-dioctanoyl-2-linoleyl-sn-glycerol (C8:0-C18:2-C8:0) (MLM) and 1,3-dilinoyl-2-octanoyl-sn-glycerol (C18:2-C8:0-C18:2) (LML). A previously optimised SMEDDS formulation for halofantrine, comprising of triglyceride, Cremophor EL, Maisine 35-1 and ethanol was selected for bioavailability assessment. The extent of lymphatic transport via the thoracic duct was 17.9% of the dose for the animals dosed with the MLM SMEDDS and 27.4% for LML. Also the plasma availability was affected by the triglyceride incorporated into the multi-component delivery system and availabilities of 56.9% (MLM) and 37.2% (LML) were found. These data indicate that the pharmaceutical scientist can use the structure of the lipid to affect the relative contribution of the two absorption pathways. The MLM formulation produced a total bioavailability of 74.9%, which is higher than the total absorption previously observed after post-prandial administration. This could indicate the utility of disperse lipid-base formulations based on structured triglycerides for the oral delivery of halofantrine, and potentially other lipophilic drugs.

[A day in the busy obstetric unit from the anesthesiologist point of view, experience at the Cleveland clinic; Cleveland, Ohio].

PubMed

Ootaki, Chiyo; Barsoum, Sabri

2009-10-01

Cleveland Clinic Labor and Delivery Unit is a syntactical delivery facility and comprised of 16 delivery rooms, 3 operating rooms, 3 triage rooms, and 1 recovery room that has a capacity of 6 beds, 43 postpartum rooms, 2 nurseries, and 1 neonatal intensive care unit (NICU). Cleveland Clinic Labor and Delivery Unit (LDU) had 3,691 delivery cases in 2007. The ratio of neuraxial analgesia (NA) during labor is 84.2% (2,348/ 2,787), using epidural anesthesia or combined spinalepidural anesthesia (CSEA). This article introduces the obstetrical (OB) anesthesia practice at the Cleveland Clinic and our novel anesthetic regime as typical of one typical busy day.

Alkali metal ion battery with bimetallic electrode

DOEpatents

Boysen, Dane A; Bradwell, David J; Jiang, Kai; Kim, Hojong; Ortiz, Luis A; Sadoway, Donald R; Tomaszowska, Alina A; Wei, Weifeng; Wang, Kangli

2015-04-07

Electrochemical cells having molten electrodes having an alkali metal provide receipt and delivery of power by transporting atoms of the alkali metal between electrode environments of disparate chemical potentials through an electrochemical pathway comprising a salt of the alkali metal. The chemical potential of the alkali metal is decreased when combined with one or more non-alkali metals, thus producing a voltage between an electrode comprising the molten the alkali metal and the electrode comprising the combined alkali/non-alkali metals.

Studies of aggregated nanoparticles steering during magnetic-guided drug delivery in the blood vessels

NASA Astrophysics Data System (ADS)

Hoshiar, Ali Kafash; Le, Tuan-Anh; Amin, Faiz Ul; Kim, Myeong Ok; Yoon, Jungwon

2017-04-01

Magnetic-guided targeted drug delivery (TDD) systems can enhance the treatment of diverse diseases. Despite the potential and promising results of nanoparticles, aggregation prevents precise particle guidance in the vasculature. In this study, we developed a simulation platform to investigate aggregation during steering of nanoparticles using a magnetic field function. The magnetic field function (MFF) comprises a positive and negative pulsed magnetic field generated by electromagnetic coils, which prevents adherence of particles to the vessel wall during magnetic guidance. A commonly used Y-shaped vessel was simulated and the performance of the MFF analyzed; the experimental data were in agreement with the simulation results. Moreover, the effects of various parameters on magnetic guidance were evaluated and the most influential identified. The simulation results presented herein will facilitate more precise guidance of nanoparticles in vivo.

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

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

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

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

Automated hybridization/imaging device for fluorescent multiplex DNA sequencing

DOEpatents

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

1995-11-28

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

Automated hybridization/imaging device for fluorescent multiplex DNA sequencing

DOEpatents

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

1995-01-01

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

Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy

PubMed Central

Oh, Keun Sang; Kim, Kyungim; Yoon, Byeong Deok; Lee, Hye Jin; Park, Dal Yong; Kim, Eun-yeong; Lee, Kiho; Seo, Jae Hong; Yuk, Soon Hong

2016-01-01

A mixture of docetaxel (DTX) and Solutol® HS 15 (Solutol) transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs) with a DTX-loaded Solutol nanodroplet (as template NPs) core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm) were observed to have an increased average diameter (from 11.7 nm to 156.1 nm) and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects. PMID:27042062

Novel polymerizable surfactants with pH-sensitive amphiphilicity and cell membrane disruption for efficient siRNA delivery.

PubMed

Wang, Xu-Li; Ramusovic, Sergej; Nguyen, Thanh; Lu, Zheng-Rong

2007-01-01

Small interfering RNA (siRNA) is a promising new therapeutic modality that can specifically silence disease-related genes. The main challenge for successful clinical development of therapeutic siRNA is the lack of efficient delivery systems. In this study, we have designed and synthesized a small library of novel multifunctional siRNA carriers, polymerizable surfactants with pH-sensitive amphiphilicity based on the hypothesis that pH-sensitive amphiphilicity and environmentally sensitive siRNA release can result in efficient siRNA delivery. The polymerizable surfactants comprise a protonatable amino head group, two cysteine residues, and two lipophilic tails. The surfactants demonstrated pH-sensitive amphiphilic hemolytic activity or cell membrane disruption with rat red blood cells. Most of the surfactants resulted in low hemolysis at pH 7.4 and high hemolysis at reduced pH (6.5 and 5.4). The pH-sensitive cell membrane disruption can facilitate endosomal-lysosomal escape of siRNA delivery systems at the endosomal-lysosomal pH. The surfactants formed compact nanoparticles (160-260 nm) with siRNA at N/P ratios of 8 and 10 via charge complexation with the amino head group, lipophilic condensation, and autoxidative polymerization of dithiols. The siRNA complexes with the surfactants demonstrated low cytotoxicity. The cellular siRNA delivery efficiency and RNAi activity of the surfactants correlated well with their pH-sensitive amphiphilic cell membrane disruption. The surfactants mediated 40-88% silencing of luciferase expression with 100 nM siRNA and 35-75% with 20 nM siRNA in U87-luc cells. Some of the surfactants resulted in similar or higher gene silencing efficiency than TransFast. EHCO with no hemolytic activity at pH 7.4 and 6.5 and high hemolytic activity at pH 5.4 resulted in the best siRNA delivery efficiency. The polymerizable surfactants with pH-sensitive amphiphilicity are promising for efficient siRNA delivery.

Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery

NASA Astrophysics Data System (ADS)

Hayward, Stephen L.; Francis, David M.; Sis, Matthew J.; Kidambi, Srivatsan

2015-10-01

The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) “(PLL/SPS)4.5” followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited HALNP monolayer further facilitated complete nanoparticle immobilization, cell adhesion, and provided nanoparticle confinement for controlled linear release profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the first study to demonstrate the successful embedment of a translatable lipid based nanocarrier into a substrate that allows for temporal and spatial release of both hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we believe the development of our HALNP embedded PEM system is significant and will catalyze the usage of substrate mediated delivery platforms in biomedical applications.

Creating Accountable Care Organizations: The Extended Hospital Medical Staff

PubMed Central

Fisher, Elliott S.; Staiger, Douglas O.; Bynum, Julie P.W.; Gottlieb, Daniel J.

2007-01-01

Many current policies and approaches to performance measurement and payment reform focus on individual providers; they risk reinforcing the fragmented care and lack of coordination experienced by patients with serious illness. In this paper we show that Medicare beneficiaries receive most of their care from relatively coherent local delivery systems comprising physicians and the hospitals where they work or admit their patients. Efforts to create accountable care organizations at this level—the extended hospital medical staff—deserve consideration as a potential means of improving the quality and lowering the cost of care. PMID:17148490

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2011-08-01

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

Preventive medical care in remote Aboriginal communities in the Northern Territory: a follow-up study of the impact of clinical guidelines, computerised recall and reminder systems, and audit and feedback.

PubMed

Bailie, Ross S; Togni, Samantha J; Si, Damin; Robinson, Gary; d'Abbs, Peter H N

2003-07-30

Interventions to improve delivery of preventive medical services have been shown to be effective in North America and the UK. However, there are few studies of the extent to which the impact of such interventions has been sustained, or of the impact of such interventions in disadvantaged populations or remote settings. This paper describes the trends in delivery of preventive medical services following a multifaceted intervention in remote community health centres in the Northern Territory of Australia. The intervention comprised the development and dissemination of best practice guidelines supported by an electronic client register, recall and reminder systems and associated staff training, and audit and feedback. Clinical records in seven community health centres were audited at regular intervals against best practice guidelines over a period of three years, with feedback of audit findings to health centre staff and management. Levels of service delivery varied between services and between communities. There was an initial improvement in service levels for most services following the intervention, but improvements were in general not fully sustained over the three year period. Improvements in service delivery are consistent with the international experience, although baseline and follow-up levels are in many cases higher than reported for comparable studies in North America and the UK. Sustainability of improvements may be achieved by institutionalisation of relevant work practices and enhanced health centre capacity.

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

PubMed

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

2010-07-01

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

Characterization of gelation process and drug release profile of thermosensitive liquid lecithin/poloxamer 407 based gels as carriers for percutaneous delivery of ibuprofen.

PubMed

Djekic, Ljiljana; Krajisnik, Danina; Martinovic, Martina; Djordjevic, Dragana; Primorac, Marija

2015-07-25

Suitability of liquid lecithin (i.e., solution of lecithin in soy bean oil with ∼ 60% w/w of phospholipids) for formation of gels, upon addition of water solution of poloxamer 407, was investigated, and formulated systems were evaluated as carriers for percutaneous delivery of ibuprofen. Formulation study of pseudo-ternary system liquid lecithin/poloxamer 407/water at constant liquid lecithin/poloxamer 407 mass ratio (2.0) revealed that minimum concentrations of liquid lecithin and poloxamer 407 required for formation of gel like systems were 15.75% w/w and 13.13% w/w, respectively, while the maximum content of water was 60.62% w/w. The systems comprising water concentrations in a range from 55 to 60.62% w/w were soft semisolids suitable for topical application, and they were selected for physicochemical and biopharmaceutical evaluation. Analysis of conductivity results and light microscopy examination revealed that investigated systems were water dilutable dispersions of spherical oligolamellar associates of phospholipids and triglyceride molecules in the copolymer water solution. Rheological behavior evaluation results indicated that the investigated gels were thermosensitive shear thinning systems. Ibuprofen (5% w/w) was incorporated by dispersing into the previously prepared carriers. Drug-loaded systems were physically stable at storage temperature from 5 ± 3°C to 40 ± 2°C, for 30 days. In vitro ibuprofen release was in accordance with the Higuchi model (rH>0.95) and sustained for 12h. The obtained results implicated that formulated LLPBGs, optimized regarding drug release and organoleptic properties, represent promising carriers for sustained percutaneous drug delivery of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Combustion process for synthesis of carbon nanomaterials from liquid hydrocarbon

DOEpatents

Diener, Michael D.; Alford, J. Michael; Nabity, James; Hitch, Bradley D.

2007-01-02

The present invention provides a combustion apparatus for the production of carbon nanomaterials including fullerenes and fullerenic soot. Most generally the combustion apparatus comprises one or more inlets for introducing an oxygen-containing gas and a hydrocarbon fuel gas in the combustion system such that a flame can be established from the mixed gases, a droplet delivery apparatus for introducing droplets of a liquid hydrocarbon feedstock into the flame, and a collector apparatus for collecting condensable products containing carbon nanomaterials that are generated in the combustion system. The combustion system optionally has a reaction zone downstream of the flame. If this reaction zone is present the hydrocarbon feedstock can be introduced into the flame, the reaction zone or both.

Self-assembled lipid--polymer hybrid nanoparticles: a robust drug delivery platform.

PubMed

Zhang, Liangfang; Chan, Juliana M; Gu, Frank X; Rhee, June-Wha; Wang, Andrew Z; Radovic-Moreno, Aleksandar F; Alexis, Frank; Langer, Robert; Farokhzad, Omid C

2008-08-01

We report the engineering of a novel lipid-polymer hybrid nanoparticle (NP) as a robust drug delivery platform, with high drug encapsulation yield, tunable and sustained drug release profile, excellent serum stability, and potential for differential targeting of cells or tissues. The NP comprises three distinct functional components: (i) a hydrophobic polymeric core where poorly water-soluble drugs can be encapsulated; (ii) a hydrophilic polymeric shell with antibiofouling properties to enhance NP stability and systemic circulation half-life; and (iii) a lipid monolayer at the interface of the core and the shell that acts as a molecular fence to promote drug retention inside the polymeric core, thereby enhancing drug encapsulation efficiency, increasing drug loading yield, and controlling drug release. The NP is prepared by self-assembly through a single-step nanoprecipitation method in a reproducible and predictable manner, making it potentially suitable for scale-up.

Self-Assembled Lipid-Polymer Hybrid Nanoparticles: A Robust Drug Delivery Platform

PubMed Central

Zhang, Liangfang; Chan, Juliana M; Gu, Frank X; Rhee, June-Wha; Wang, Andrew Z; Radovic-Moreno, Aleksandar F; Alexis, Frank; Langer, Robert; Farokhzad, Omid C

2014-01-01

We report the engineering of a novel lipid-polymer hybrid nanoparticle (NP) as a robust drug delivery platform, with high drug encapsulation yield, tunable and sustained drug release profile, excellent serum stability, and potential for differential targeting of cells or tissues. The NP is comprised of three distinct functional components: i) a hydrophobic polymeric core where poorly water-soluble drugs can be encapsulated; ii) a hydrophilic polymeric shell with anti-biofouling properties to enhance NP stability and systemic circulation half-life; and iii) a lipid monolayer at the interface of the core and the shell that acts as a molecular fence to promote drug retention inside the polymeric core, thereby enhancing drug encapsulation efficiency, increasing drug loading yield, and controlling drug release. The NP is prepared by self-assembly through a single-step nanoprecipitation method in a reproducible and predictable manner, making it potentially suitable for scale-up PMID:19206374

Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced DNA vaccine delivery.

PubMed

Nawwab Al-Deen, F M; Selomulya, C; Kong, Y Y; Xiang, S D; Ma, C; Coppel, R L; Plebanski, M

2014-02-01

Dendritic cells (DC) targeting vaccines require high efficiency for uptake, followed by DC activation and maturation. We used magnetic vectors comprising polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles, with hyaluronic acid (HA) of different molecular weights (<10 and 900 kDa) to reduce cytotoxicity and to facilitate endocytosis of particles into DCs via specific surface receptors. DNA encoding Plasmodium yoelii merozoite surface protein 1-19 and a plasmid encoding yellow fluorescent gene were added to the magnetic complexes with various % charge ratios of HA: PEI. The presence of magnetic fields significantly enhanced DC transfection and maturation. Vectors containing a high-molecular-weight HA with 100% charge ratio of HA: PEI yielded a better transfection efficiency than others. This phenomenon was attributed to their longer molecular chains and higher mucoadhesive properties aiding DNA condensation and stability. Insights gained should improve the design of more effective DNA vaccine delivery systems.

High-intensity focused ultrasound (HIFU) array system for image-guided ablative therapy (IGAT)

NASA Astrophysics Data System (ADS)

Kaczkowski, Peter J.; Keilman, George W.; Cunitz, Bryan W.; Martin, Roy W.; Vaezy, Shahram; Crum, Lawrence A.

2003-06-01

Recent interest in using High Intensity Focused Ultrasound (HIFU) for surgical applications such as hemostasis and tissue necrosis has stimulated the development of image-guided systems for non-invasive HIFU therapy. Seeking an all-ultrasound therapeutic modality, we have developed a clinical HIFU system comprising an integrated applicator that permits precisely registered HIFU therapy delivery and high quality ultrasound imaging using two separate arrays, a multi-channel signal generator and RF amplifier system, and a software program that provides the clinician with a graphical overlay of the ultrasound image and therapeutic protocol controls. Electronic phasing of a 32 element 2 MHz HIFU annular array allows adjusting the focus within the range of about 4 to 12 cm from the face. A central opening in the HIFU transducer permits mounting a commercial medical imaging scanhead (ATL P7-4) that is held in place within a special housing. This mechanical fixture ensures precise coaxial registration between the HIFU transducer and the image plane of the imaging probe. Recent enhancements include development of an acoustic lens using numerical simulations for use with a 5-element array. Our image-guided therapy system is very flexible and enables exploration of a variety of new HIFU therapy delivery and monitoring approaches in the search for safe, effective, and efficient treatment protocols.

Ophthalmic gels: Past, present and future.

PubMed

Al-Kinani, Ali A; Zidan, Ghada; Elsaid, Naba; Seyfoddin, Ali; Alani, Adam W G; Alany, Raid G

2018-02-15

Aqueous gels formulated using hydrophilic polymers (hydrogels) along with those based on stimuli responsive polymers (in situ gelling or gel forming systems) continue to attract increasing interest for various eye health-related applications. They allow the incorporation of a variety of ophthalmic pharmaceuticals to achieve therapeutic levels of drugs and bioactives at target ocular sites. The integration of sophisticated drug delivery technologies such as nanotechnology-based ones with intelligent and environment responsive systems can extend current treatment duration to provide more clinically relevant time courses (weeks and months instead of hours and days) which will inevitably reduce dose frequency, increase patient compliance and improve clinical outcomes. Novel applications and design of contact lenses and intracanalicular delivery devices along with the move towards integrating gels into various drug delivery devices like intraocular pumps, injections and implants has the potential to reduce comorbidities caused by glaucoma, corneal keratopathy, cataract, diabetic retinopathies and age-related macular degeneration. This review describes ophthalmic gelling systems with emphasis on mechanism of gel formation and application in ophthalmology. It provides a critical appraisal of the techniques and methods used in the characterization of ophthalmic preformed gels and in situ gelling systems along with a thorough insight into the safety and biocompatibility of these systems. Newly developed ophthalmic gels, hydrogels, preformed gels and in situ gelling systems including the latest in the area of stimuli responsive gels, molecularly imprinted gels, nanogels, 3D printed hydrogels; 3D printed devices comprising ophthalmic gels are covered. Finally, new applications of gels in the production of artificial corneas, corneal wound healing and hydrogel contact lenses are described. Copyright © 2017 Elsevier B.V. All rights reserved.

Lipid based nanoemulsifying resveratrol for improved physicochemical characteristics, in vitro cytotoxicity and in vivo antiangiogenic efficacy.

PubMed

Pund, Swati; Thakur, Rohit; More, Umesh; Joshi, Amita

2014-08-01

Resveratrol, a dietary non-flavonoid polyphenolic phytoalexin, has gained attention in cancer chemoprevention. However, poor aqueous solubility and cellular bioavailability has limited its therapeutic application. We formulated a lipid based delivery system of resveratrol with self nanoemulsifying ability. Several edible and safe lipids, surfactants and cosolvents were screened for solubilization of resevratrol. Developed formulation comprised of Acrysol K 150 as a lipid and mixture of Labrasol and Transcutol HP as the surfactant system, as these components showed higher solubility. Pseudoternary phase diagram was constructed to identify the region of nanoemulsification. The formulations showed rapid emulsification with an average globule diameter; 85nm to 120nm and slight negative zeta potential. The nanocompositions exhibited cloud point above 55°C and were stable toward the gastrointestinal pH and thermodynamic stress testing. As compared to pristine resveratrol, the developed delivery system showed significant increase in vitro cytotoxicity in MCF-7 breast cancer cells. In vivo chick chorioallantoic membrane assay revealed enhanced antiangiogenic activity of composition with high lipid level. Briefly, lipid based nanoemulsifying resveratrol dramatically enhanced the anticancer and antiangiogenic activities, thus increasing its potential application in cancer chemotherapy. Copyright © 2014 Elsevier B.V. All rights reserved.

The system with zwitterionic lactose-based surfactant for complexation and delivery of small interfering ribonucleic acid—A structural and spectroscopic study

NASA Astrophysics Data System (ADS)

Skupin, Michalina; Sobczak, Krzysztof; Zieliński, Ryszard; Kozak, Maciej

2016-05-01

Systems suitable for the effective preparation of complexes with siRNA (small interfering RNA) are at the center of interest in the area of research work on the delivery of the RNA-based drugs (RNA-therapeutics). This article presents results of a study on the structural effects associated with siRNA complexation by a surfactant comprising a lactose group (N-(3-propanesulfone)-N-dodecyl-amino-beta-D-lactose hydrochloride, LA12). The double stranded siRNA oligomer (21 base pairs) used in this study is responsible for silencing a gene that can be important in the therapy of myotonic dystrophy type 1. The obtained siRNA/LA12 lipoplexes were studied using the methods of small angle scattering of synchrotron radiation, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and electrophoretic mobility tests. Lipoplexes form in solution stable lamellar or cubic phases. The surfactant selected for the study shows much lower cytotoxicity and good complexation abilities of siRNA than dicationic or polycationic surfactants.

The system with zwitterionic lactose-based surfactant for complexation and delivery of small interfering ribonucleic acid—A structural and spectroscopic study

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

Skupin, Michalina; Sobczak, Krzysztof; Zieliński, Ryszard

Systems suitable for the effective preparation of complexes with siRNA (small interfering RNA) are at the center of interest in the area of research work on the delivery of the RNA-based drugs (RNA-therapeutics). This article presents results of a study on the structural effects associated with siRNA complexation by a surfactant comprising a lactose group (N-(3-propanesulfone)-N-dodecyl-amino-beta-D-lactose hydrochloride, LA12). The double stranded siRNA oligomer (21 base pairs) used in this study is responsible for silencing a gene that can be important in the therapy of myotonic dystrophy type 1. The obtained siRNA/LA12 lipoplexes were studied using the methods of small anglemore » scattering of synchrotron radiation, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and electrophoretic mobility tests. Lipoplexes form in solution stable lamellar or cubic phases. The surfactant selected for the study shows much lower cytotoxicity and good complexation abilities of siRNA than dicationic or polycationic surfactants.« less

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved.

PubMed

Inrig, Stephen J; Tiro, Jasmin A; Melhado, Trisha V; Argenbright, Keith E; Craddock Lee, Simon J

2014-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. To better understand how to implement a decentralized regional delivery "hub & spoke" model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow's RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow's RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting.

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved

PubMed Central

Inrig, Stephen J.; Tiro, Jasmin A.; Melhado, Trisha V.; Argenbright, Keith E.; Craddock Lee, Simon J.

2017-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. Objectives To better understand how to implement a decentralized regional delivery “hub & spoke” model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow’s RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Methods and Design The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow’s RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. Discussion This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting. PMID:28713882

Impact of Delivery Modality, Student GPA, and Time-Lapse since High School on Successful Completion of College-Level Math after Taking Developmental Math

ERIC Educational Resources Information Center

Acosta, Diane; North, Teresa Lynn; Avella, John

2016-01-01

This study considered whether delivery modality, student GPA, or time since high school affected whether 290 students who had completed a developmental math series as a community college were able to successfully complete college-level math. The data used in the study was comprised of a 4-year period historical student data from Odessa College…

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

PubMed

Hoyer, Herbert; Greindl, Melanie; Bernkop-Schnürch, Andreas

2009-02-01

A new oral patch delivery system has been designed to increase the overall oral bioavailability of drugs within the gastrointestinal tract. The patch system consists of four layered films: a mucoadhesive matrix layer, a water insoluble backing layer, a middle layer and an enteric surface layer. The separation layer between the two matrix layers contained lactose, starch and confectioners' sugar. The matrix layer, exhibiting a diameter of 2.5 mm and a weight of 5 mg, comprised Polycarbophil-cysteine conjugate (49%), fluoresceine isothiocyanate-dextran (26%), glutathione (5%), and mannitol (20%). A standard tablet formulation consisting of the same matrix served as control. Entire fluoresceine isothiocyanate-dextran (FD(4)) was released from the delivery system within 2 h. For in vivo studies patch systems were administered orally to male Sprague-Dawley rats. Maximum FD(4) concentration in blood of the patch system was 46.1 +/- 8.9 ng/mL and was reached 3 h after administration. In contrast c(max) of control tablets displayed 50.5 +/- 14.9 ng/mL after 2 h and the absorption of FD(4) after administration in oral solution was negligible. The absolute bioavailability of orally administered patch systems and control tablets was 0.54% and 0.32% respectively. Results of this study indicate that a prolonged and higher oral bioavailability of FD(4) is obtained with patches than with tablets.

[Quality of birth care in maternity hospitals of Rio de Janeiro, Brazil].

PubMed

d'Orsi, Eleonora; Chor, Dóra; Giffin, Karen; Angulo-Tuesta, Antonia; Barbosa, Gisele Peixoto; Gama, Andrea de Souza; Reis, Ana Cristina; Hartz, Zulmira

2005-08-01

To evaluate the quality of birth care based on the World Health Organization guidelines. A case-control study was carried out in a public and a private maternity hospitals contracted by the Brazilian Health System in the city of Rio de Janeiro, Brazil, from October 1998 to March 1999. The sample comprised 461 women in the public maternity hospital (230 vaginal deliveries and 231 Cesarean sections) and 448 women in the private one (224 vaginal deliveries and 224 Cesarean sections). Data was collected through interviews with puerperal women and review of medical records. A summarization score of quality of delivery care was constructed. There was low frequency of practices that should be encouraged, such as having an accompanying person (1% in the private hospital for both vaginal delivery and C-sections), freedom of movements throughout labor (9.6% of C-sections in the public hospital and 9.9% of vaginal deliveries in the private hospital) and breastfeeding in the delivery room (6.9% of C-sections in the public hospital and 8.0% of C-sections in the private hospital). There was a high frequency of known harmful practices such as enema administration (38.4%); routine pubic shaving; routine intravenous infusion (88.8%); routine use of oxytocin (64.4%), strict bed rest throughout labor (90.1%) and routine supine position in labor (98.7%) in vaginal deliveries. The best summarizing scores were seen in the public maternity hospital. The two maternity hospitals have a high frequency of interventions during birth care. In spite of providing care to higher risk pregnant women, the public maternity hospital has a less interventionist profile than the private one. Procedures carried out on a routine basis should be pondered based on evidence of their benefits.

Targeting homeostasis in drug delivery using bioresponsive hydrogel microforms.

PubMed

Wilson, A Nolan; Guiseppi-Elie, Anthony

2014-01-30

A drug delivery platform comprising a biocompatible, bioresponsive hydrogel and possessing a covalently tethered peptide-drug conjugate was engineered to achieve stasis, via a closed control loop, of the external biochemical activity of the actuating protease. The delivery platform contains a peptide-drug conjugate covalently tethered to the hydrogel matrix, which in the presence of the appropriate protease, was cleaved and the drug released into the bathing environment. This platform was developed and investigated in silico using a finite element modeling (FEM) approach. Firstly, the primary governing phenomena guiding drug release profiles were investigated, and it was confirmed that under transport-limited conditions, the diffusion of the enzyme within the hydrogel and the coupled enzyme kinetics accurately model the system and are in agreement with published results. Secondly, the FEM model was used to investigate the release of a competitive protease inhibitor, MAG283, via cleavage of Acetyl-Pro-Leu-Gly|Leu-MAG-283 by MMP9 in order to achieve targeted homeostasis of MMP-9 activity, such as in the pathophysiology of chronic wounds, via closed-loop feedback control. The key engineering parameters for the delivery device are the radii of the hydrogel microspheres and the concentration of the peptide-inhibitor conjugate. Homeostatic drug delivery, where the focus turns away from the drug release rate and turns toward achieving targeted control of biochemical activity within a biochemical pathway, is an emerging approach in drug delivery methodologies for which the potential has not yet been fully realized. Copyright © 2013 Elsevier B.V. All rights reserved.

Telepsychiatry as an Economically Better Model for Reaching the Unreached: A Retrospective Report from South India

PubMed Central

Moirangthem, Sydney; Rao, Sabina; Kumar, Channaveerachari Naveen; Narayana, Manjunatha; Raviprakash, Neelaveni; Math, Suresh Bada

2017-01-01

Aim: In a resource-poor country such as India, telepsychiatry could be an economical method to expand health-care services. This study was planned to compare the costing and feasibility of three different service delivery models. The end user was a state-funded long-stay Rehabilitation Center (RC) for the homeless. Methodology: Model A comprised patients going to a tertiary care center for clinical care, Model B was community outreach service, and Model C comprised telepsychiatry services. The costing included expenses incurred by the health system to complete a single consultation for a patient on an outpatient basis. It specifically excluded the cost borne by the care-receiver. No patients were interviewed for the study. Results: The RC had 736 inmates, of which 341 had mental illness of very long duration. On comparing the costing, Model A costed 6047.5 INR (100$), Model B costed 577.1 INR (9.1$), and Model C costed 137.2 INR (2.2$). Model C was found fifty times more economical when compared to Model A and four times more economical when compared to Model B. Conclusion: Telepsychiatry services connecting tertiary center and a primary health-care center have potential to be an economical model of service delivery compared to other traditional ones. This resource needs to be tapped in a better fashion to reach the unreached. PMID:28615759

Telepsychiatry as an Economically Better Model for Reaching the Unreached: A Retrospective Report from South India.

PubMed

Moirangthem, Sydney; Rao, Sabina; Kumar, Channaveerachari Naveen; Narayana, Manjunatha; Raviprakash, Neelaveni; Math, Suresh Bada

2017-01-01

In a resource-poor country such as India, telepsychiatry could be an economical method to expand health-care services. This study was planned to compare the costing and feasibility of three different service delivery models. The end user was a state-funded long-stay Rehabilitation Center (RC) for the homeless. Model A comprised patients going to a tertiary care center for clinical care, Model B was community outreach service, and Model C comprised telepsychiatry services. The costing included expenses incurred by the health system to complete a single consultation for a patient on an outpatient basis. It specifically excluded the cost borne by the care-receiver. No patients were interviewed for the study. The RC had 736 inmates, of which 341 had mental illness of very long duration. On comparing the costing, Model A costed 6047.5 INR (100$), Model B costed 577.1 INR (9.1$), and Model C costed 137.2 INR (2.2$). Model C was found fifty times more economical when compared to Model A and four times more economical when compared to Model B. Telepsychiatry services connecting tertiary center and a primary health-care center have potential to be an economical model of service delivery compared to other traditional ones. This resource needs to be tapped in a better fashion to reach the unreached.

Nanochanneled Device and Related Methods

NASA Technical Reports Server (NTRS)

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

2016-01-01

A nanochannel delivery device and method of manufacturing and use. The nanochannel delivery device comprises an inlet, an outlet, and a nanochannel. The nanochannel may be oriented parallel to the primary plane of the nanochannel delivery device. The inlet and outlet may be in direct fluid communication with the nanochannel. Considerable advances have been made in the field oftherapeutic agent (e.g. drug) delivery technology over thelast three decades, resulting in many breakthroughs in clinicalmedicine. The creation of therapeutic agent deliverydevices that are capable of delivering therapeutic agents incontrolled ways is still a challenge. One of the majorrequirements for an implantable drug delivery device iscontrolled release of therapeutic agents, ranging from smalldrug molecules to larger biological molecules. It is particularlydesirable to achieve a continuous passive drug releaseprofile consistent with zero order kinetics whereby theconcentration of drug in the bloodstream remains constantthroughout an extended delivery period.These devices have the potential to improve therapeuticefficacy, diminish potentially life-threatening side effects,improve patient compliance, minimize the intervention ofhealthcare personnel, reduce the duration of hospital stays,and decrease the diversion of regulated drugs to abusiveuses.Nanochannel delivery devices may be used in drug deliveryproducts for the effective administration of drugs. Inaddition, nanochannel delivery devices can be used in otherapplications where controlled release of a substance overtime is needed. Embodiments of this invention comprise a nanochanneldelivery device having nanochannels within a structureconfigured to yield high mechanical strength and high flowrates. Various fabrication protocols may be used to form thenanochannel delivery device. Embodiments of the fabricateddevices feature horizontal nanochannel lay-out (e.g., thenanochannel is parallel to the primary plane of the device),high molecule transport rate, high mechanical strength,optional multilayered lay-out, amenability to select channellining materials, and possible transparent top cover. Basedon silicon microfabrication technology, the dimensions ofthe nanochannel area as well as concomitant microchannelareas can be precisely controlled, thus providing a predictable,reliable, constant release rate of drug (or other) moleculesover an extended time period. In certain embodiments,the nanochannel delivery device can be used to builda multilayered nanochannel structure.

Immobilized lipid-bilayer materials

DOEpatents

Sasaki, Darryl Y.; Loy, Douglas A.; Yamanaka, Stacey A.

2000-01-01

A method for preparing encapsulated lipid-bilayer materials in a silica matrix comprising preparing a silica sol, mixing a lipid-bilayer material in the silica sol and allowing the mixture to gel to form the encapsulated lipid-bilayer material. The mild processing conditions allow quantitative entrapment of pre-formed lipid-bilayer materials without modification to the material's spectral characteristics. The method allows for the immobilization of lipid membranes to surfaces. The encapsulated lipid-bilayer materials perform as sensitive optical sensors for the detection of analytes such as heavy metal ions and can be used as drug delivery systems and as separation devices.

Power and Thermal Technology for Air and Space-Scientific Research Program Delivery Order 0003: Electrical Technology Component Development

DTIC Science & Technology

2007-03-01

specific contact resistivity of Ti/AlNi/Au 24 21 The full view 3D model of the IGBT ………………………………….. 25 22 2D temperature distribution of the SiC...comprised of multiple materials. The representative geometry of a Si isolated gated bipolar transistor ( IGBT ) was chosen for the initial simulation...samples annealed at 650°C for 30 minutes in either the tube furnace with an oxygen gettering system or in the vacuum chamber, represented the superior

International Space Station (ISS)

NASA Image and Video Library

2002-03-08

Launched aboard the Space Shuttle Endeavor on June 6, 2002, these four astronauts comprised the prime crew for NASA's STS-111 mission. Astronaut Kenneth D. Cockrell (front right) was mission commander, and astronaut Paul S. Lockhart (front left) was pilot. Astronauts Philippe Perrin (rear left), representing the French Space Agency, and Franklin R. Chang-Diaz were mission specialists assigned to extravehicular activity (EVA) work on the International Space Station (ISS). In addition to the delivery and installation of the Mobile Base System (MBS), this crew dropped off the Expedition Five crew members at the orbital outpost, and brought back the Expedition Four trio at mission's end.

Instrumental rotation for persistent fetal occiput posterior position: a way to decrease maternal and neonatal injury?

PubMed

Vidal, Fabien; Simon, Caroline; Cristini, Christelle; Arnaud, Catherine; Parant, Olivier

2013-01-01

To evaluate immediate perineal and neonatal morbidity associated with instrumental rotations performed with Thierry's spatulas for the management of persistent posterior occiput (OP) positions. Retrospective study including all persistent occiput posterior positions with vaginal OP delivery, from August 2006 to September 2007. Occiput anterior deliveries following successful instrumental rotation were included as well. We compared maternal and neonatal immediate outcomes between spontaneous deliveries, rotational and non rotational assisted deliveries, using χ(2) and Anova tests. 157 patients were enrolled, comprising 46 OP spontaneous deliveries, 58 assisted OP deliveries and 53 deliveries after rotational procedure. Instrumental rotation failed in 9 cases. Mean age and parity were significantly higher in the spontaneous delivery group, while labor duration was shorter. There were no significant differences in the rate of severe perineal tears and neonatal adverse outcomes between the 3 groups. Instrumental rotation using Thierry's spatulas was not associated with a reduced risk of maternal and neonatal morbidity for persistent OP deliveries. Further studies are required to define the true interest of such procedure in modern obstetrics.

Instrumental Rotation for Persistent Fetal Occiput Posterior Position: A Way to Decrease Maternal and Neonatal Injury?

PubMed Central

Vidal, Fabien; Simon, Caroline; Cristini, Christelle; Arnaud, Catherine; Parant, Olivier

2013-01-01

Objective To evaluate immediate perineal and neonatal morbidity associated with instrumental rotations performed with Thierry’s spatulas for the management of persistent posterior occiput (OP) positions. Methods Retrospective study including all persistent occiput posterior positions with vaginal OP delivery, from August 2006 to September 2007. Occiput anterior deliveries following successful instrumental rotation were included as well. We compared maternal and neonatal immediate outcomes between spontaneous deliveries, rotational and non rotational assisted deliveries, using χ2 and Anova tests. Results 157 patients were enrolled, comprising 46 OP spontaneous deliveries, 58 assisted OP deliveries and 53 deliveries after rotational procedure. Instrumental rotation failed in 9 cases. Mean age and parity were significantly higher in the spontaneous delivery group, while labor duration was shorter. There were no significant differences in the rate of severe perineal tears and neonatal adverse outcomes between the 3 groups. Conclusion Instrumental rotation using Thierry’s spatulas was not associated with a reduced risk of maternal and neonatal morbidity for persistent OP deliveries. Further studies are required to define the true interest of such procedure in modern obstetrics. PMID:24205122

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

PubMed

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

2008-02-28

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

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

PubMed

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

2017-02-14

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

Dry-powder formulations of non-covalent protein complexes with linear or miktoarm copolymers for pulmonary delivery.

PubMed

Nieto-Orellana, Alejandro; Coghlan, David; Rothery, Malcolm; Falcone, Franco H; Bosquillon, Cynthia; Childerhouse, Nick; Mantovani, Giuseppe; Stolnik, Snow

2018-04-05

Pulmonary delivery of protein therapeutics has considerable clinical potential for treating both local and systemic diseases. However, poor protein conformational stability, immunogenicity and protein degradation by proteolytic enzymes in the lung are major challenges to overcome for the development of effective therapeutics. To address these, a family of structurally related copolymers comprising polyethylene glycol, mPEG 2k , and poly(glutamic acid) with linear A-B (mPEG 2k -lin-GA) and miktoarm A-B 3 (mPEG 2k -mik-(GA) 3 ) macromolecular architectures was investigated as potential protein stabilisers. These copolymers form non-covalent nanocomplexes with a model protein (lysozyme) which can be formulated into dry powders by spray-drying using common aerosol excipients (mannitol, trehalose and leucine). Powder formulations with excellent aerodynamic properties (fine particle fraction of up to 68%) were obtained with particle size (D 50 ) in the 2.5 µm range, low moisture content (<5%), and high glass transitions temperatures, i.e. formulation attributes all suitable for inhalation application. In aqueous medium, dry powders rapidly disintegrated into the original polymer-protein nanocomplexes which provided protection towards proteolytic degradation. Taken together, the present study shows that dry powders based on (mPEG 2k -polyGA)-protein nanocomplexes possess potentials as an inhalation delivery system. Copyright © 2018 Elsevier B.V. All rights reserved.

A receptor-targeted nanocomplex vector system optimized for respiratory gene transfer.

PubMed

Tagalakis, Aristides D; McAnulty, Robin J; Devaney, James; Bottoms, Stephen E; Wong, John B; Elbs, Martin; Writer, Michele J; Hailes, Helen C; Tabor, Alethea B; O'Callaghan, Christopher; Jaffe, Adam; Hart, Stephen L

2008-05-01

Synthetic vectors for cystic fibrosis (CF) gene therapy are required that efficiently and safely transfect airway epithelial cells, rather than alveolar epithelial cells or macrophages, and that are nonimmunogenic, thus allowing for repeated delivery. We have compared several vector systems against these criteria including GL67, polyethylenimine (PEI) 22 and 25 kd and two new, synthetic vector formulations, comprising a cationic, receptor-targeting peptide K(16)GACSERSMNFCG (E), and the cationic liposomes (L) DHDTMA/DOPE or DOSEP3/DOPE. The lipid and peptide formulations self assemble into receptor-targeted nanocomplexes (RTNs) LED-1 and LED-2, respectively, on mixing with plasmid (D). LED-1 transfected airway epithelium efficiently, while LED-2 and GL67 preferentially transfected alveolar cells. PEI transfected airway epithelial cells with high efficiency, but was more toxic to the mice than the other formulations. On repeat dosing, LED-1 was equally as effective as the single dose, while GL67 was 30% less effective and PEI 22 kd displayed a 90% reduction of efficiency on repeated delivery. LED-1 thus was the only formulation that fulfilled the criteria for a CF gene therapy vector while GL67 and LED-2 may be appropriate for other respiratory diseases. Opportunities for PEI depend on a solution to its toxicity problems. LED-1 formulations were stable to nebulization, the most appropriate delivery method for CF.

Diamond encapsulated photovoltaics for transdermal power delivery.

PubMed

Ahnood, A; Fox, K E; Apollo, N V; Lohrmann, A; Garrett, D J; Nayagam, D A X; Karle, T; Stacey, A; Abberton, K M; Morrison, W A; Blakers, A; Prawer, S

2016-03-15

A safe, compact and robust means of wireless energy transfer across the skin barrier is a key requirement for implantable electronic devices. One possible approach is photovoltaic (PV) energy delivery using optical illumination at near infrared (NIR) wavelengths, to which the skin is highly transparent. In the work presented here, a subcutaneously implantable silicon PV cell, operated in conjunction with an external NIR laser diode, is developed as a power delivery system. The biocompatibility and long-term biostability of the implantable PV is ensured through the use of an hermetic container, comprising a transparent diamond capsule and platinum wire feedthroughs. A wavelength of 980 nm is identified as the optimum operating point based on the PV cell's external quantum efficiency, the skin's transmission spectrum, and the wavelength dependent safe exposure limit of the skin. In bench-top experiments using an external illumination intensity of 0.7 W/cm(2), a peak output power of 2.7 mW is delivered to the implant with an active PV cell dimension of 1.5 × 1.5 × 0.06 mm(3). This corresponds to a volumetric power output density of ~20 mW/mm(3), significantly higher than power densities achievable using inductively coupled coil-based approaches used in other medical implant systems. This approach paves the way for further ministration of bionic implants. Copyright © 2015 Elsevier B.V. All rights reserved.

Guidebook for value for money assessment.

DOT National Transportation Integrated Search

2013-12-01

The Federal Highway Administrations (FHWA) Office of Innovative Program Delivery (OIPD) has developed a Public-Private Partnership (P3) Toolkit comprising tools and guidance documents to assist in educating public sector policymakers, legislative ...

21 CFR 201.150 - Drugs; processing, labeling, or repacking.

Code of Federal Regulations, 2010 CFR

2010-04-01

... part thereof, from such establishment, become void ab initio if the drug comprising such shipment... ab initio with respect to the person who introduced such shipment or delivery into interstate...

21 CFR 201.150 - Drugs; processing, labeling, or repacking.

Code of Federal Regulations, 2013 CFR

2013-04-01

... part thereof, from such establishment, become void ab initio if the drug comprising such shipment... ab initio with respect to the person who introduced such shipment or delivery into interstate...

21 CFR 201.150 - Drugs; processing, labeling, or repacking.

Code of Federal Regulations, 2012 CFR

2012-04-01

... part thereof, from such establishment, become void ab initio if the drug comprising such shipment... ab initio with respect to the person who introduced such shipment or delivery into interstate...

21 CFR 201.150 - Drugs; processing, labeling, or repacking.

Code of Federal Regulations, 2011 CFR

2011-04-01

... part thereof, from such establishment, become void ab initio if the drug comprising such shipment... ab initio with respect to the person who introduced such shipment or delivery into interstate...

21 CFR 201.150 - Drugs; processing, labeling, or repacking.

Code of Federal Regulations, 2014 CFR

2014-04-01

... part thereof, from such establishment, become void ab initio if the drug comprising such shipment... ab initio with respect to the person who introduced such shipment or delivery into interstate...

Multiple feed powder splitter

DOEpatents

Lewis, Gary K.; Less, Richard M.

2001-01-01

A device for providing uniform powder flow to the nozzles when creating solid structures using a solid fabrication system such as the directed light fabrication (DLF) process. In the DLF process, gas entrained powders are passed through the focal point of a moving high-power laser light which fuses the particles in the powder to a surface being built up in layers. The invention is a device providing uniform flow of gas entrained powders to the nozzles of the DLF system. The device comprises a series of modular splitters which are slidably interconnected and contain an integral flow control mechanism. The device can take the gas entrained powder from between one to four hoppers and split the flow into eight tubular lines which feed the powder delivery nozzles of the DLF system.

Multiple feed powder splitter

DOEpatents

Lewis, Gary K.; Less, Richard M.

2002-01-01

A device for providing uniform powder flow to the nozzles when creating solid structures using a solid fabrication system such as the directed light fabrication (DLF) process. In the DLF process, gas entrained powders are passed through the focal point of a moving high-power laser light which fuses the particles in the powder to a surface being built up in layers. The invention is a device providing uniform flow of gas entrained powders to the nozzles of the DLF system. The device comprises a series of modular splitters which are slidably interconnected and contain an integral flow control mechanism. The device can take the gas entrained powder from between one to four hoppers and split the flow into eight tubular lines which feed the powder delivery nozzles of the DLF system.

Design of a line-VISAR interferometer system for the Sandia Z Machine

NASA Astrophysics Data System (ADS)

Galbraith, J.; Austin, K.; Baker, J.; Bettencourt, R.; Bliss, E.; Celeste, J.; Clancy, T.; Cohen, S.; Crosley, M.; Datte, P.; Fratanduono, D.; Frieders, G.; Hammer, J.; Jackson, J.; Johnson, D.; Jones, M.; Koen, D.; Lusk, J.; Martinez, A.; Massey, W.; McCarville, T.; McLean, H.; Raman, K.; Rodriguez, S.; Spencer, D.; Springer, P.; Wong, J.

2017-08-01

A joint team comprised of Lawrence Livermore National Laboratory (LLNL) and Sandia National Laboratory (SNL) personnel is designing a line-VISAR (Velocity Interferometer System for Any Reflector) for the Sandia Z Machine, Z Line-VISAR. The diagnostic utilizes interferometry to assess current delivery as a function of radius during a magnetically-driven implosion. The Z Line-VISAR system is comprised of the following: a two-leg line-VISAR interferometer, an eight-channel Gated Optical Imager (GOI), and a fifty-meter transport beampath to/from the target of interest. The Z Machine presents unique optomechanical design challenges. The machine utilizes magnetically driven pulsed power to drive a target to elevated temperatures and pressures useful for high energy density science. Shock accelerations exceeding 30g and a strong electromagnetic pulse (EMP) are generated during the shot event as the machine discharges currents of over 25 million amps. Sensitive optical components must be protected from shock loading, and electrical equipment must be adequately shielded from the EMP. The optical design must accommodate temperature and humidity fluctuations in the facility as well as airborne hydrocarbons from the pulsed power components. We will describe the engineering design and concept of operations of the Z Line-VISAR system. Focus will be on optomechanical design.

Using Survival Analysis to Understand Patterns of Sustainment within a System-Driven Implementation of Multiple Evidence-Based Practices for Children's Mental Health Services.

PubMed

Brookman-Frazee, Lauren; Zhan, Chanel; Stadnick, Nicole; Sommerfeld, David; Roesch, Scott; Aarons, Gregory A; Innes-Gomberg, Debbie; Bando, Lillian; Lau, Anna S

2018-01-01

Evidence-based practice (EBP) implementation requires substantial resources in workforce training; yet, failure to achieve long-term sustainment can result in poor return on investment. There is limited research on EBP sustainment in mental health services long after implementation. This study examined therapists' continued vs. discontinued practice delivery based on administrative claims for reimbursement for six EBPs [Cognitive Behavioral Interventions for Trauma in Schools (CBITS), Child-Parent Psychotherapy, Managing and Adapting Practices (MAP), Seeking Safety (SS), Trauma-Focused Cognitive Behavior Therapy (TF-CBT), and Positive Parenting Program] adopted in a system-driven implementation effort in public mental health services for children. Our goal was to identify agency and therapist factors associated with a sustained EBP delivery. Survival analysis (i.e., Kaplan-Meier survival functions, log-rank tests, and Cox regressions) was used to analyze 19 fiscal quarters (i.e., approximately 57 months) of claims data from the Prevention and Early Intervention Transformation within the Los Angeles County Department of Mental Health. These data comprised 2,322,389 claims made by 6,873 therapists across 88 agencies. Survival time was represented by the time elapsed from therapists' first to final claims for each practice and for any of the six EBPs. Results indicate that therapists continued to deliver at least one EBP for a mean survival time of 21.73 months (median = 18.70). When compared to a survival curve of the five other EBPs, CBITS, SS, and TP demonstrated a higher risk of delivery discontinuation, whereas MAP and TF-CBT demonstrated a lower risk of delivery discontinuation. A multivariate Cox regression model revealed that agency (centralization and service setting) and therapist (demographics, discipline, and case-mix characteristics) characteristics were significantly associated with risk of delivery discontinuation for any of the six EBPs. This study illustrates a novel application of survival analysis to administrative claims data in system-driven implementation of multiple EBPs. Findings reveal variability in the long-term continuation of therapist-level delivery of EBPs and highlight the importance of both agency and workforce characteristics in the sustained delivery of EBPs. Findings direct the field to potential targets of sustainment interventions (e.g., strategic assignment of therapists to EBP training and strategic selection of EBPs by agencies).

Defining an at-risk population for obstetric anal sphincter laceration.

PubMed

Minaglia, Steven M; Kimata, Chieko; Soules, Karen A; Pappas, Tamara; Oyama, Ian A

2009-11-01

The purpose of this study was to calculate the number of cesarean deliveries needed to prevent 1 case of obstetric anal sphincter laceration associated with operative vaginal delivery in an at-risk cohort. An institutional, computerized database was used to analyze women with obstructed labor who could have been managed by either operative vaginal or cesarean delivery from September 2006 to March 2008. Women with 1 or more of the following diagnoses comprised the cohort: cephalopelvic disproportion (CPD), arrest of descent, maternal exhaustion, and fetal distress. Fifty (23.9%) out of a total of 209 women managed by operative vaginal delivery experienced an anal sphincter laceration compared to none of 254 women in the cesarean delivery group (P < .0001). The ARR therefore was 23.9% (95% confidence interval, 18.1-29.7) and the NNT was 4.2 (95% confidence interval, 3.4-5.5). Five cesarean deliveries are needed to prevent 1 anal sphincter laceration associated with operative vaginal delivery in this cohort.

Variable delivery, fixed displacement pump

DOEpatents

Sommars, Mark F.

2001-01-01

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

Self-assembling peptide amphiphiles and related methods for growth factor delivery

DOEpatents

Stupp, Samuel I [Chicago, IL; Donners, Jack J. J. M.; Silva, Gabriel A [Chicago, IL; Behanna, Heather A [Chicago, IL; Anthony, Shawn G [New Stanton, PA

2009-06-09

Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

Self-assembling peptide amphiphiles and related methods for growth factor delivery

DOEpatents

Stupp, Samuel I [Chicago, IL; Donners, Jack J. J. M.; Silva, Gabriel A [Chicago, IL; Behanna, Heather A [Chicago, IL; Anthony, Shawn G [New Stanton, PA

2012-03-20

Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

Self-assembling peptide amphiphiles and related methods for growth factor delivery

DOEpatents

Stupp, Samuel I; Donners, Jack J.J.M.; Silva, Gabriel A; Behanna, Heather A; Anthony, Shawn G

2013-11-12

Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

Operative vaginal delivery in case of persistent occiput posterior position after manual rotation failure: a 6-month follow-up on pelvic floor function.

PubMed

Guerby, Paul; Parant, Olivier; Chantalat, Elodie; Vayssiere, Christophe; Vidal, Fabien

2018-07-01

To compare the short- and long-term perineal consequences (at 6 months postpartum) and short-term neonatal consequences of instrumental rotation (IR) to those induced by assisted delivery (AD) in the occiput posterior (OP) position, in case of manual rotation failure. A prospective observational cohort study; tertiary referral hospital including all women presenting with persistent OP position who delivered vaginally after manual rotation failure with attempted IR or AD in OP position from September 2015 to October 2016. Maternal and neonatal outcomes of all attempted IR deliveries were compared with OP operative vaginal deliveries. Main outcomes measured were pelvic floor function at 6 months postpartum including Wexner score for anal incontinence and ICIQ-FLUTS for urinary symptoms. Perineal morbidity comprised severe perineal tears, corresponding to third and fourth degree lacerations. Fetal morbidity parameters comprised low neonatal Apgar scores, acidaemia, major and minor fetal injuries and neonatal intensive care unit admissions. Among 5265 women, 495 presented with persistent OP positions (9.4%) and 111 delivered after manual rotation failure followed by AD delivery: 58 in the IR group and 53 in the AD in OP group. The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.7% vs. 24.5%; p < 0.001) without increasing neonatal morbidity. At 6 months postpartum, AD in OP position was associated with higher rate of anal incontinence (30% vs. 5.5%, p = 0.001) and with more urinary symptoms, dyspareunia and perineal pain. OP operative deliveries are associated with significant perineal morbidity and pelvic floor dysfunction at 6 months postpartum.

Advances in RNAi therapeutic delivery to leukocytes using lipid nanoparticles.

PubMed

Ramishetti, Srinivas; Landesman-Milo, Dalit; Peer, Dan

2016-11-01

Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials for liver diseases and solid tumors, but remain a challenge for manipulating leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest pathogens and defend the body through a complex network. They are also involved in the pathogeneses of inflammation, viral infection, autoimmunity and cancers. Modulating gene expression in leukocytes using siRNAs holds great promise to treat leukocyte-mediated diseases. Leukocytes are notoriously hard to transduce with siRNAs and are spread throughout the body often located deep in tissues, therefore developing an efficient systemic delivery strategy is still a challenge. Here, we discuss recent advances in siRNA delivery to leukocyte subsets such as macrophages, monocytes, dendritic cells and lymphocytes. We focus mainly on lipid-based nanoparticles (LNPs) comprised of new generation of ionizable lipids and their ability to deliver siRNA to primary or malignant leukocytes in a targeted manner. Special emphasis is made on LNPs targeted to subsets of leukocytes and we detail a novel microfluidic mixing technology that could aid in changing the landscape of process development of LNPs from a lab tool to a potential novel therapeutic modality.

Transforming youth mental health services and supports in Ireland.

PubMed

Illback, Robert J; Bates, Tony

2011-02-01

Young people in the Republic of Ireland do not have access to appropriate mental health services and supports, necessitating transformational change in delivery systems. Describe ongoing development and change efforts facilitated by Headstrong--The National Centre for Youth Mental Health. Discusses findings from a national needs assessment, core strategies within the change initiative, progress in system-building, and preliminary descriptive and outcome data. Five demonstration sites comprised of four counties and a city neighbourhood are operational and preliminary data are promising with respect to implementation and outcomes. Effective change initiatives require vision and leadership, competence- and capacity-building, participative planning and engagement, adequate and thoughtfully deployed resources, and a comprehensive change management approach. © 2011 Blackwell Publishing Asia Pty Ltd.

Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain.

PubMed

Patel, Mayur M; Patel, Bhoomika M

2017-02-01

CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting. Several approaches have been investigated to allow therapeutics to cross the BBB. As the molecular structure of the BBB is better elucidated, several key approaches for brain targeting include physiological transport mechanisms such as adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, cell-mediated endocytosis, and the use of peptide vectors. Drug-delivery approaches comprise delivery from microspheres, biodegradable wafers, and colloidal drug-carrier systems (e.g., liposomes, nanoparticles, nanogels, dendrimers, micelles, nanoemulsions, polymersomes, exosomes, and quantum dots). The current review discusses the latest advancements in these approaches, with a major focus on articles published in 2015 and 2016. In addition, we also cover the alternative delivery routes, such as intranasal and convection-enhanced diffusion methods, and disruption of the BBB for brain targeting.

Guidebook for risk assessment in public private partnerships.

DOT National Transportation Integrated Search

2013-12-01

The Federal Highway Administrations (FHWA) Office of Innovative Program Delivery (OIPD) has developed a P3 Toolkit comprising tools and guidance documents to assist in educating public sector policymakers, legislative and executive staff, and tran...

21 CFR 701.9 - Exemptions from labeling requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., become void ab initio if the cosmetic comprising such shipment, delivery, or part is adulterated or... a cosmetic under paragraph (a)(2) of this section shall become void ab initio with respect to the...

The economic, institutional, and political determinants of public health delivery system structures.

PubMed

Ingram, Richard C; Scutchfield, F Douglas; Mays, Glen P; Bhandari, Michelyn W

2012-01-01

A typology of local public health systems was recently introduced, and a large degree of structural transformation over time was discovered in the systems analyzed. We present a qualitative exploration of the factors that determine variation and change in the seven structural configurations that comprise the local public health delivery system typology. We applied a 10-item semistructured telephone interview protocol to representatives from the local health agency in two randomly selected systems from each configuration--one that had maintained configuration over time and one that had changed configuration over time. We assessed the interviews for patterns of variation between the configurations. Four key determinants of structural change emerged: availability of financial resources, interorganizational relationships, public health agency organization, and political relationships. Systems that had changed were more likely to experience strengthened partnerships between public health agencies and other community organizations and enjoy support from policy makers, while stable systems were more likely to be characterized by strong partnerships between public health agencies and other governmental bodies and less supportive relationships with policy makers. This research provides information regarding the determinants of system change, and may help public health leaders to better prepare for the impacts of change in the areas discussed. It may also help those who are seeking to implement change to determine the contextual factors that need to be in place before change can happen, or how best to implement change in the face of contextual factors that are beyond their control.

Expanding Alternative Delivery Systems.

ERIC Educational Resources Information Center

Baltzer, Jan A.

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

Transportation systems analyses: Volume 1: Executive Summary

NASA Astrophysics Data System (ADS)

1993-05-01

The principal objective of this study is to accomplish a systems engineering assessment of the nation's space transportation infrastructure. This analysis addresses the necessary elements to perform man delivery and return, cargo transfer, cargo delivery, payload servicing, and the exploration of the Moon and Mars. Specific elements analyzed, but not limited to, include the Space Exploration Initiative (SEI), the National Launch System (NLS), the current expendable launch vehicle (ELV) fleet, ground facilities, the Space Station Freedom (SSF), and other civil, military and commercial payloads. The performance of this study entails maintaining a broad perspective on the large number of transportation elements that could potentially comprise the U.S. space infrastructure over the next several decades. To perform this systems evaluation, top-level trade studies are conducted to enhance our understanding of the relationships between elements of the infrastructure. This broad 'infrastructure-level perspective' permits the identification of preferred infrastructures. Sensitivity analyses are performed to assure the credibility and usefulness of study results. This executive summary of the transportation systems analyses (TSM) semi-annual report addresses the SSF logistics resupply. Our analysis parallels the ongoing NASA SSF redesign effort. Therefore, there could be no SSF design to drive our logistics analysis. Consequently, the analysis attempted to bound the reasonable SSF design possibilities (and the subsequent transportation implications). No other strategy really exists until after a final decision is rendered on the SSF configuration.

A Closer Look at 804: A Summary of Considerations for DoD Program Managers

DTIC Science & Technology

2011-12-01

aimed at changing the culture from one that is fo- cused typically on a single delivery to a new model that comprises multiple deliveries to es...under the Agency CIOs, and de - velop flexible budget models that align with modular development. • Launch an interactive platform for pre-RFP agency...permission@sei.cmu.edu. TM Carnegie Mellon Software Engineering Institute (stylized), Carnegie Mellon Software Engineering Institute (and de - sign), Simplex

Solvent exchange-induced in situ forming gel comprising ethyl cellulose-antimicrobial drugs.

PubMed

Phaechamud, Thawatchai; Mahadlek, Jongjan

2015-10-15

Solvent-exchanged in situ forming gel is a drug delivery system which is in sol form before administration. When it contacts with the body fluid, then the water miscible organic solvent dissipates and water penetrates into the system, leading the polymer precipitation as in situ gel at the site of injection. The aim of this research was to study the parameters affecting the gel properties, drug release and antimicrobial activities of the in situ forming gels prepared from ethyl cellulose (EC) dissolved in N-methyl pyrrolidone (NMP) to deliver the antimicrobial agents (doxycycline hyclate, metronidazole and benzyl peroxide) for periodontitis treatment. The gel appearance, pH, viscosity, rheology, syringeability, gel formation, rate of water diffusion into the gels, in vitro degradation, drug release behavior and antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans and Porphyrommonas gingivalis were determined. Increasing the amount of EC increased the viscosity of system while still exhibiting Newtonian flow and increased the work of syringeability whereas decreased the releasing of drug. The system transformed into the rigid gel formation after being injected into the simulated gingival crevicular fluid. The developed systems containing 5% w/w antimicrobial agent showed the antimicrobial activities against all test bacteria. Thus the developed solvent exchange-induced in situ forming gels comprising EC-antimicrobial drugs exhibited potential use for periodontitis treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

ALternate Site Cardiac ResYNChronization (ALSYNC): a prospective and multicentre study of left ventricular endocardial pacing for cardiac resynchronization therapy.

PubMed

Morgan, John M; Biffi, Mauro; Gellér, László; Leclercq, Christophe; Ruffa, Franco; Tung, Stanley; Defaye, Pascal; Yang, Zhongping; Gerritse, Bart; van Ginneken, Mireille; Yee, Raymond; Jais, Pierre

2016-07-14

The ALternate Site Cardiac ResYNChronization (ALSYNC) study evaluated the feasibility and safety of left ventricular endocardial pacing (LVEP) using a market-released pacing lead implanted via a single pectoral access by a novel atrial transseptal lead delivery system. ALSYNC was a prospective clinical investigation with a minimum of 12-month follow-up in 18 centres of cardiac resynchronization therapy (CRT)-indicated patients, who had failed or were unsuitable for conventional CRT. The ALSYNC system comprises the investigational lead delivery system and LVEP lead. Patients required warfarin therapy post-implant. The primary study objective was safety at 6-month follow-up, which was defined as freedom from complications related to the lead delivery system, implant procedure, or the lead ≥70%. The ALSYNC study enrolled 138 patients. The LVEP lead implant success rate was 89.4%. Freedom from complications meeting the definition of primary endpoint was 82.2% at 6 months (95% CI 75.6-88.8%). In the study, 14 transient ischaemic attacks (9 patients, 6.8%), 5 non-disabling strokes (5 patients, 3.8%), and 23 deaths (17.4%) were observed. No death was from a primary endpoint complication. At 6 months, the New York Heart Association class improved in 59% of patients, and 55% had LV end-systolic volume reduction of 15% or greater. Those patients enrolled after CRT non-response showed similar improvement with LVEP. The ALSYNC study demonstrates clinical feasibility, and provides an early indication of possible benefit and risk of LVEP. NCT01277783. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

21 CFR 501.100 - Animal food; exemptions from labeling.

Code of Federal Regulations, 2014 CFR

2014-04-01

... become void ab initio if the food comprising such shipment, delivery, or part is adulterated or... a food under paragraph (d)(2) of this section shall become void ab initio with respect to the person...

Transdermal delivery of therapeutic agent

NASA Technical Reports Server (NTRS)

Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

2008-01-01

A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

A novel folate-modified self-microemulsifying drug delivery system of curcumin for colon targeting.

PubMed

Zhang, Lin; Zhu, Weiwei; Yang, Chunfen; Guo, Hongxia; Yu, Aihua; Ji, Jianbo; Gao, Yan; Sun, Min; Zhai, Guangxi

2012-01-01

The objective of this study was to prepare, characterize, and evaluate a folate-modified self-microemulsifying drug delivery system (FSMEDDS) with the aim to improve the solubility of curcumin and its delivery to the colon, facilitating endocytosis of FSMEDDS mediated by folate receptors on colon cancer cells. Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. Then, three lipophilic folate derivatives (folate-polyethylene glycol-distearoylphosphatidylethanolamine, folate-polyethylene glycol-cholesteryl hemisuccinate, and folate-polyethylene glycol-cholesterol) used as a surfactant were added to curcumin-loaded SMEDDS formulations. An in situ colon perfusion method in rats was used to optimize the formulation of FSMEDDS. Curcumin-loaded FSMEDDS was then filled into colon-targeted capsules and the in vitro release was investigated. Cytotoxicity studies and cellular uptake studies was used in this research. The optimal formulation of FSMEDDS obtained with the established in situ colon perfusion method in rats was comprised of 57.5% Cremophor(®) EL, 32.5% Transcutol(®) HP, 10% Capryol™ 90, and a small amount of folate-polyethylene glycol-cholesteryl hemisuccinate (the weight ratio of folate materials to Cremophor EL was 1:100). The in vitro release results indicated that the obtained formulation of curcumin could reach the colon efficiently and release the drug immediately. Cellular uptake studies analyzed with fluorescence microscopy and flow cytometry indicated that the FSMEDDS formulation could efficiently bind with the folate receptors on the surface of positive folate receptors cell lines. In addition, FSMEDDS showed greater cytotoxicity than SMEDDS in the above two cells. FSMEDDS-filled colon-targeted capsules are a potential carrier for colon delivery of curcumin.

Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide/protein in the treatment of ocular diseases

PubMed Central

Patel, Sulabh P.; Vaishya, Ravi; Patel, Ashaben; Agrahari, Vibhuti; Pal, Dhananjay; Mitra, Ashim K.

2016-01-01

This manuscript is focused on the development of pentablock (PB) copolymer based sustained release formulation for the treatment of posterior segment ocular diseases. We have successfully synthesized biodegradable and biocompatible PB copolymers for the preparation of nanoparticles (NPs) and thermosensitive gel. Achieving high drug loading with hydrophilic biotherapeutics (peptides /proteins) is a challenging task. Moreover, small intravitreal injection volume (≤100 μL) requires high loading to develop a long term (6 months) sustained release formulation. We have successfully investigated various formulation parameters to achieve maximum peptide/protein (octreotide, insulin, lysozyme, IgG-Fab, IgG, and catalase) loading in PB NPs. Improvement in drug loading can facilitate delivery of larger doses of therapeutic proteins via limited injection volume. A composite formulation comprised of NPs in gel system exhibited sustained release (without burst effect) of peptides and proteins, may serve as a platform technology for the treatment of posterior segment ocular diseases. PMID:26964498

Effectively delivering a unique hsp90 inhibitor using star polymers.

PubMed

Kim, Seong Jong; Ramsey, Deborah M; Boyer, Cyrille; Davis, Thomas P; McAlpine, Shelli R

2013-07-25

We report the synthesis of a novel heat shock protein 90 (hsp90) inhibitor conjugated to a star polymer. Using reversible addition-fragmentation chain-transfer (RAFT) polymerization, we prepared star polymers comprised of PEG attached to a predesigned functional core. The stars were cross-linked using disulfide linkers, and a tagged version of our hsp90 inhibitor was conjugated to the polymer core to generate nanoparticles (14 nM). Dynamic light scattering showed that the nanoparticles were stable in cell growth media for 5 days, and HPLC analysis of compound-release at 3 different pH values showed that release was pH dependent. Cell cytotoxicity studies and confocal microscopy verify that our hsp90 inhibitor was delivered to cells using this nanoparticle delivery system. Further, delivery of our hsp90 inhibitor using star polymer induces apoptosis by a caspase 3-dependent pathway. These studies show that we can deliver our hsp90 inhibitor effectively using star polymers, and induce apoptosis by the same pathway as the parent compound.

Parallel NGO Networks for HIV Control: Risks and Opportunities for NGO Contracting

PubMed Central

Zaidi, Shehla; Gul, Xaher; Nishtar, Noureen

2013-01-01

Policy measures for preventive and promotive services are increasingly reliant on contracting of NGOs. Contracting is a neo-liberal response relying on open market competition for service delivery tenders. In contracting of health services a common assumption is a monolithic NGO market. A case study of HIV control in Pakistan shows that in reality the NGO market comprises of parallel NGO networks having widely different service packages, approaches and agendas. These parallel networks had evolved over time due to vertical policy agendas. Contracting of NGOs for provision of HIV services was faced with uneven capacities and turf rivalries across both NGO networks. At the same time contracting helped NGO providers belonging to different clusters to move towards standardized service delivery for HIV prevention. Market based measures such as contracting need to be accompanied with wider policy and system measures that overcome silos in NGO working by facilitating a common construct on the health issue, cohesive priorities and integrated working. PMID:23445705

Self-assembled nanoparticles comprising aptide-SN38 conjugates for use in targeted cancer therapy

NASA Astrophysics Data System (ADS)

Kim, Hyungjun; Lee, Yonghyun; Kang, Sukmo; Choi, Minsuk; Lee, Soyoung; Kim, Sunghyun; Gujrati, Vipul; Kim, Jinjoo; Jon, Sangyong

2016-12-01

Self-assembled nanoparticles (NPs) have been intensively utilized as cancer drug delivery carriers because hydrophobic anticancer drugs may be efficiently loaded into the particle cores. In this study, we synthesized and evaluated the therapeutic index of self-assembled NPs chemically conjugated to a fibronectin extra domain B-specific peptide (APTEDB) and an anticancer agent SN38. The APTEDB-SN38 formed self-assembled structures with a diameter of 58 ± 3 nm in an aqueous solution and displayed excellent drug loading, solubility, and stability properties. A pharmacokinetic study revealed that the blood circulation half-life of SN38 following injection of the APTEDB-SN38 NPs was markedly higher than that of the small molecule CPT-11. The APTEDB-SN38 NPs delivered SN38 to tumor sites by both passive and active targeting. Finally, the APTEDB-SN38 NPs exhibited potent antitumor activities and low toxicities against EDB-expressing tumors (LLC, U87MG) in mice. This system merits further preclinical and clinical investigations for SN38 delivery.

Gene Therapy in Heart Failure.

PubMed

Fargnoli, Anthony S; Katz, Michael G; Bridges, Charles R; Hajjar, Roger J

2017-01-01

Heart failure is a significant burden to the global healthcare system and represents an underserved market for new pharmacologic strategies, especially therapies which can address root cause myocyte dysfunction. Modern drugs, surgeries, and state-of-the-art interventions are costly and do not improve survival outcome measures. Gene therapy is an attractive strategy, whereby selected gene targets and their associated regulatory mechanisms can be permanently managed therapeutically in a single treatment. This in theory could be sustainable for the patient's life. Despite the promise, however, gene therapy has numerous challenges that must be addressed together as a treatment plan comprising these key elements: myocyte physiologic target validation, gene target manipulation strategy, vector selection for the correct level of manipulation, and carefully utilizing an efficient delivery route that can be implemented in the clinic to efficiently transfer the therapy within safety limits. This chapter summarizes the key developments in cardiac gene therapy from the perspective of understanding each of these components of the treatment plan. The latest pharmacologic gene targets, gene therapy vectors, delivery routes, and strategies are reviewed.

Scaffold of Selenium Nanovectors and Honey Phytochemicals for Inhibition of Pseudomonas aeruginosa Quorum Sensing and Biofilm Formation.

PubMed

Prateeksha; Singh, Braj R; Shoeb, M; Sharma, S; Naqvi, A H; Gupta, Vijai K; Singh, Brahma N

2017-01-01

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro . Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery.

On-board processing satellite network architecture and control study

NASA Technical Reports Server (NTRS)

Campanella, S. Joseph; Pontano, B.; Chalmers, H.

1987-01-01

For satellites to remain a vital part of future national and international communications, system concepts that use their inherent advantages to the fullest must be created. Network architectures that take maximum advantage of satellites equipped with onboard processing are explored. Satellite generations must accommodate various services for which satellites constitute the preferred vehicle of delivery. Such services tend to be those that are widely dispersed and present thin to medium loads to the system. Typical systems considered are thin and medium route telephony, maritime, land and aeronautical radio, VSAT data, low bit rate video teleconferencing, and high bit rate broadcast of high definition video. Delivery of services by TDMA and FDMA multiplexing techniques and combinations of the two for individual and mixed service types are studied. The possibilities offered by onboard circuit switched and packet switched architectures are examined and the results strongly support a preference for the latter. A detailed design architecture encompassing the onboard packet switch and its control, the related demand assigned TDMA burst structures, and destination packet protocols for routing traffic are presented. Fundamental onboard hardware requirements comprising speed, memory size, chip count, and power are estimated. The study concludes with identification of key enabling technologies and identifies a plan to develop a POC model.

Compressor-fan unitary structure for air conditioning system

NASA Astrophysics Data System (ADS)

Dreiman, N.

2015-08-01

An extremely compact, therefore space saving unitary structure of short axial length is produced by radial integration of a revolving piston rotary compressor and an impeller of a centrifugal fan. The unitary structure employs single motor to run as the compressor so the airflow fan and eliminates duality of motors, related power supply and control elements. Novel revolving piston rotary compressor which provides possibility for such integration comprises the following: a suction gas delivery system which provides cooling of the motor and supplies refrigerant into the suction chamber under higher pressure (supercharged); a modified discharge system and lubricating oil supply system. Axial passages formed in the stationary crankshaft are used to supply discharge gas to a condenser, to return vaporized cooling agent from the evaporator to the suction cavity of the compressor, to pass a lubricant and to accommodate wiring supplying power to the unitary structure driver -external rotor electric motor.

Leveraging the U.S. Criminal Justice System to Access Women for HIV Interventions.

PubMed

Meyer, Jaimie P; Muthulingam, Dharushana; El-Bassel, Nabila; Altice, Frederick L

2017-12-01

The criminal justice (CJ) system can be leveraged to access women for HIV prevention and treatment programs. Research is lacking on effective implementation strategies tailored to the specific needs of CJ-involved women. We conducted a scoping review of published studies in English from the United States that described HIV interventions, involved women or girls, and used the CJ system as an access point for sampling or intervention delivery. We identified 350 studies and synthesized data from 42 unique interventions, based in closed (n = 26), community (n = 7), or multiple/other CJ settings (n = 9). A minority of reviewed programs incorporated women-specific content or conducted gender-stratified analyses. CJ systems are comprised of diverse access points, each with unique strengths and challenges for implementing HIV treatment and prevention programs for women. Further study is warranted to develop women-specific and trauma-informed content and evaluate program effectiveness.

C-Language Integrated Production System, Version 6.0

NASA Technical Reports Server (NTRS)

Riley, Gary; Donnell, Brian; Ly, Huyen-Anh Bebe; Ortiz, Chris

1995-01-01

C Language Integrated Production System (CLIPS) computer programs are specifically intended to model human expertise or other knowledge. CLIPS is designed to enable research on, and development and delivery of, artificial intelligence on conventional computers. CLIPS 6.0 provides cohesive software tool for handling wide variety of knowledge with support for three different programming paradigms: rule-based, object-oriented, and procedural. Rule-based programming: representation of knowledge as heuristics - essentially, rules of thumb that specify set of actions performed in given situation. Object-oriented programming: modeling of complex systems comprised of modular components easily reused to model other systems or create new components. Procedural-programming: representation of knowledge in ways similar to those of such languages as C, Pascal, Ada, and LISP. Version of CLIPS 6.0 for IBM PC-compatible computers requires DOS v3.3 or later and/or Windows 3.1 or later.

Designing personal exercise monitoring employing multiple modes of delivery: implications from a qualitative study on heart rate monitoring.

PubMed

Segerståhl, Katarina; Oinas-Kukkonen, Harri

2011-12-01

Various personal monitoring technologies have been introduced for supporting regular physical activity, which is of critical importance in reducing the risks of several chronic diseases. Recent studies suggest that combining multiple modes of delivery, such as text messages and mobile monitoring devices with web applications, holds potential for effectively supporting physical exercise. Of particular interest is how the functionality and content of these systems should be distributed across the different modes for successful outcomes. The aim of this study was to: (a) investigate how users incorporate a system employing two modes of delivery - a wearable heart rate monitor and a web service - into their training and (b) to analyze benefits and limitations in personal exercise monitoring and how they relate to the different modes in use. A qualitative field study employing diaries and semi-structured interviews was carried out with 30 participants who used a heart rate monitoring system comprising a wearable heart rate monitor, Polar FT60 and a web service, Polar Personal Trainer for a period of 21 days. The data were systematically analyzed to identify specific benefits and limitations associated with the system characteristics and modes as perceived by the end-users. The benefits include supporting exploratory learning, controlling target behavior, rectifying behaviors, motivation and logging support. The limitations are associated with information for validating the system, virtual coaching, task-technology fit, data integrity and privacy concerns. Mobile interfaces enable exploratory learning and controlling of target behaviors in situ, while web services can effectively support users' need for cognition within the early stages of adoption and long-term training with intelligent coaching functionality. This study explains several benefits and limitations in personal exercise monitoring. These can be addressed with crossmedial design, i.e., strategic distribution of functionality and content across modes within the system. Our findings suggest that personal exercise monitoring systems may be improved by more systematically combining mobile and web-based functionality. 2011 Elsevier Ireland Ltd. All rights reserved.

Status of the James Webb Space Telescope Observatory

NASA Technical Reports Server (NTRS)

Clampin, Mark

2013-01-01

The James Webb Space Telescope (JWST) is the largest cryogenic, space telescope ever built, and will address a broad range of scientific goals from first light in the universe and re-ionization, to characterization of the atmospheres of extrasolar planets. Recently, significant progress has been made in the construction of the observatory with the completion of all 21 flight mirrors that comprise the telescope's optical chain, and the start of flight instrument deliveries to the Goddard Space Flight Center. In this paper we discuss the design of the observatory, and focus on the recent milestone achievements in each of the major observatory sub-systems.

Latest advances in the manufacturing of 3D rechargeable lithium microbatteries

NASA Astrophysics Data System (ADS)

Ferrari, Stefania; Loveridge, Melanie; Beattie, Shane D.; Jahn, Marcus; Dashwood, Richard J.; Bhagat, Rohit

2015-07-01

Recent advances in micro- and nano-electromechanical systems (MEMS/NEMS) technology have led to a niche industry of diverse small-scale devices that include microsensors, micromachines and drug-delivery systems. For these devices, there is an urgent need to develop Micro Lithium Ion Batteries (MLIBs) with dimensions on the scale 1-10 mm3 enabling on-board power delivery. Unfortunately, power limitations are inherent in planar 2D cells and only the advent of 3D designs and microarchitectures will lead to a real breakthrough in the microbattery technology. During the last few years, many efforts to optimise MLIBs were discussed in literature, both in the planar and 3D configurations. This review highlights the importance of 3D microarchitectured electrodes to fabricate batteries that can be device-integrated with exceptionally high specific power density coupled with exquisite miniaturisation. A wide literature overview is provided and recent advances in manufacturing routes to 3D-MLIBs comprising materials synthesis, device formulation, device testing are herein discussed. The advent of simple, economic and easily scalable fabrication processes such as 3D printing will have a decisive role in the growing field of micropower sources and microdevices.

Non-immunogenic, hydrophilic/cationic block copolymers and uses thereof

DOEpatents

Scales, Charles W.; Huang, Faqing; McCormick, Charles L.

2010-05-18

The present invention provides novel non-immunogenic, hydrophilic/cationic block copolymers comprising a neutral-hydrophilic polymer and a cationic polymer, wherein both polymers have well-defined chain-end functionality. A representative example of such a block copolymer comprises poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly(N-[3-(dimethylamino)propyl]methacrylamide) (PDMAPMA). Also provided is a synthesis method thereof in aqueous media via reversible addition fragmentation chain transfer (RAFT) polymerization. Further provided are uses of these block copolymers as drug delivery vehicles and protection agents.

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system.

PubMed

Chen, Zhi-Qiang; Liu, Ying; Zhao, Ji-Hui; Wang, Lan; Feng, Nian-Ping

2012-01-01

Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin. A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats. The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor(®) EL:Transcutol(®) P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS. The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.

Modular radiochemistry synthesis system

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R.; Amarasekera, Bernard; Van Dam, Michael R.; Olma, Sebastian; Williams, Dirk; Eddings, Mark; Shen, Clifton Kwang-Fu

2016-11-01

A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

Modular radiochemistry synthesis system

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R.; Amarasekera, Bernard; Van Dam, R. Michael; Olma, Sebastian; Williams, Dirk; Eddings, Mark; Shen, Clifton Kwang-Fu

2015-12-15

A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

Modular radiochemistry synthesis system

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R; Amarasekera, Bernard; Van Dam, R. Michael; Olma, Sebastian; Williams, Dirk; Eddings, Mark A; Shen, Clifton Kwang-Fu

2015-02-10

A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

Integration and verification testing of the Large Synoptic Survey Telescope camera

NASA Astrophysics Data System (ADS)

Lange, Travis; Bond, Tim; Chiang, James; Gilmore, Kirk; Digel, Seth; Dubois, Richard; Glanzman, Tom; Johnson, Tony; Lopez, Margaux; Newbry, Scott P.; Nordby, Martin E.; Rasmussen, Andrew P.; Reil, Kevin A.; Roodman, Aaron J.

2016-08-01

We present an overview of the Integration and Verification Testing activities of the Large Synoptic Survey Telescope (LSST) Camera at the SLAC National Accelerator Lab (SLAC). The LSST Camera, the sole instrument for LSST and under construction now, is comprised of a 3.2 Giga-pixel imager and a three element corrector with a 3.5 degree diameter field of view. LSST Camera Integration and Test will be taking place over the next four years, with final delivery to the LSST observatory anticipated in early 2020. We outline the planning for Integration and Test, describe some of the key verification hardware systems being developed, and identify some of the more complicated assembly/integration activities. Specific details of integration and verification hardware systems will be discussed, highlighting some of the technical challenges anticipated.

Methods and apparatuses for cutting, abrading, and drilling

DOEpatents

Bingham, Dennis N.; Swainston, Richard C.; Palmer, Gary L.; Ferguson, Russell L.

2001-01-01

Methods and apparatuses for treating a surface of a work piece are described. In one implementation, a laser delivery subsystem is configured to direct a laser beam toward a treatment zone on a work surface. A cryogenic material delivery subsystem is operably coupled with the laser delivery subsystem and is configured to direct a stream comprising cryogenic material toward the treatment zone. Both the laser beam and stream cooperate to treat material of the work surface within the treatment zone. In one aspect, a nozzle assembly provides the laser beam and stream of cryogenic material along a common flow axis. In another aspect, the laser beam and stream are provided along different axes.

Understanding electrostatic charge behaviour in aircraft fuel systems

NASA Astrophysics Data System (ADS)

Ogilvy, Jill A.; Hooker, Phil; Bennett, Darrell

2015-10-01

This paper presents work on the simulation of electrostatic charge build-up and decay in aircraft fuel systems. A model (EC-Flow) has been developed by BAE Systems under contract to Airbus, to allow the user to assess the effects of changes in design or in refuel conditions. Some of the principles behind the model are outlined. The model allows for a range of system components, including metallic and non-metallic pipes, valves, filters, junctions, bends and orifices. A purpose-built experimental rig was built at the Health and Safety Laboratory in Buxton, UK, to provide comparison data. The rig comprises a fuel delivery system, a test section where different components may be introduced into the system, and a Faraday Pail for measuring generated charge. Diagnostics include wall currents, charge densities and pressure losses. This paper shows sample results from the fitting of model predictions to measurement data and shows how analysis may be used to explain some of the observed trends.

Wireless energizing system for an automated implantable sensor.

PubMed

Swain, Biswaranjan; Nayak, Praveen P; Kar, Durga P; Bhuyan, Satyanarayan; Mishra, Laxmi P

2016-07-01

The wireless drive of an automated implantable electronic sensor has been explored for health monitoring applications. The proposed system comprises of an automated biomedical sensing system which is energized through resonant inductive coupling. The implantable sensor unit is able to monitor the body temperature parameter and sends back the corresponding telemetry data wirelessly to the data recoding unit. It has been observed that the wireless power delivery system is capable of energizing the automated biomedical implantable electronic sensor placed over a distance of 3 cm from the power transmitter with an energy transfer efficiency of 26% at the operating resonant frequency of 562 kHz. This proposed method ensures real-time monitoring of different human body temperatures around the clock. The monitored temperature data have been compared with a calibrated temperature measurement system to ascertain the accuracy of the proposed system. The investigated technique can also be useful for monitoring other body parameters such as blood pressure, bladder pressure, and physiological signals of the patient in vivo using various implantable sensors.

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.

Design of a multifiber light delivery system for photoacoustic-guided surgery.

PubMed

Eddins, Blackberrie; Bell, Muyinatu A Lediju

2017-04-01

This work explores light delivery optimization for photoacoustic-guided minimally invasive surgeries, such as the endonasal transsphenoidal approach. Monte Carlo simulations were employed to study three-dimensional light propagation in tissue, comprising one or two 4-mm diameter arteries located 3 mm below bone, an absorbing metallic drill contacting the bone surface, and a single light source placed next to the 2.4-mm diameter drill shaft with a 2.9-mm diameter spherical drill tip. The optimal fiber distance from the drill shaft was determined from the maximum normalized fluence to the underlying artery. Using this optimal fiber-to-drill shaft distance, Zemax simulations were employed to propagate Gaussian beams through one or more 600 micron-core diameter optical fibers for detection on the bone surface. When the number of equally spaced fibers surrounding the drill increased, a single merged optical profile formed with seven or more fibers, determined by thresholding the resulting light profile images at 1 / e times the maximum intensity. We used these simulations to inform design requirements, build a one to seven multifiber light delivery prototype to surround a surgical drill, and demonstrate its ability to simultaneously visualize the tool tip and blood vessel targets in the absence and presence of bone. The results and methodology are generalizable to multiple interventional photoacoustic applications.

Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

NASA Astrophysics Data System (ADS)

Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan

2017-01-01

Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

Design of a multifiber light delivery system for photoacoustic-guided surgery

NASA Astrophysics Data System (ADS)

Eddins, Blackberrie; Bell, Muyinatu A. Lediju

2017-04-01

This work explores light delivery optimization for photoacoustic-guided minimally invasive surgeries, such as the endonasal transsphenoidal approach. Monte Carlo simulations were employed to study three-dimensional light propagation in tissue, comprising one or two 4-mm diameter arteries located 3 mm below bone, an absorbing metallic drill contacting the bone surface, and a single light source placed next to the 2.4-mm diameter drill shaft with a 2.9-mm diameter spherical drill tip. The optimal fiber distance from the drill shaft was determined from the maximum normalized fluence to the underlying artery. Using this optimal fiber-to-drill shaft distance, Zemax simulations were employed to propagate Gaussian beams through one or more 600 micron-core diameter optical fibers for detection on the bone surface. When the number of equally spaced fibers surrounding the drill increased, a single merged optical profile formed with seven or more fibers, determined by thresholding the resulting light profile images at 1/e times the maximum intensity. We used these simulations to inform design requirements, build a one to seven multifiber light delivery prototype to surround a surgical drill, and demonstrate its ability to simultaneously visualize the tool tip and blood vessel targets in the absence and presence of bone. The results and methodology are generalizable to multiple interventional photoacoustic applications.

Mode of Delivery and Long-Term Health-Related Quality-of-Life Outcomes: A Prospective Population-Based Study.

PubMed

Petrou, Stavros; Kim, Sung Wook; McParland, Penny; Boyle, Elaine M

2017-06-01

Relatively little is known about the effects of mode of delivery on long-term health-related quality-of-life outcomes. Furthermore, no previous study has expressed these outcomes in preference-based (utility) metrics. The study population comprised 2,161 mothers recruited from a prospective population-based study in the East Midlands of England encompassing live births and stillbirths between 32 +0 and 36 +6 weeks' gestation and a sample of term-born controls. Perinatal data were extracted from the mothers' maternity records. Health-related quality-of-life outcomes were assessed at 12 months postpartum, using the EuroQol Five Dimensions (EQ-5D) measure with responses to the EQ-5D descriptive system converted into health utility scores. Descriptive statistics and multivariable analyses were used to estimate the relationship between the mode of delivery and health-related quality-of-life outcomes. The overall health-related quality-of-life profile of the women in the study cohort mirrored that of the English adult population as revealed by national health surveys. A significantly higher proportion of women delivering by cesarean delivery reported some, moderate, severe, or extreme pain or discomfort at 12 months postpartum than women undergoing spontaneous vaginal delivery. Multivariable analyses, using the Ordinary Least Squares estimator revealed that, after controlling for maternal sociodemographic characteristics, cesarean delivery without maternal or fetal compromise was associated with a significant EQ-5D utility decrement in comparison to spontaneous vaginal delivery among all women (-0.026; p = 0.038) and among mothers of term-born infants (-0.062; p < 0.001). Among mothers of term-born infants, this result was replicated in models that controlled for all maternal and infant characteristics (utility decrement of -0.061; p < 0.001). The results were confirmed by sensitivity analyses that varied the categorization of the main exposure variable (mode of delivery) and the econometric strategy. Among mothers of term-born infants, cesarean delivery without maternal or fetal compromise is associated with poorer long-term health-related quality of life in comparison to spontaneous vaginal delivery. Further longitudinal studies are needed to understand the magnitude, trajectory, and underpinning mechanisms of health-related quality-of-life outcomes following different modes of delivery. © 2016 Wiley Periodicals, Inc.

A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms

NASA Astrophysics Data System (ADS)

Phanse, Yashdeep; Carrillo-Conde, Brenda R.; Ramer-Tait, Amanda E.; Broderick, Scott; Kong, Chang Sun; Rajan, Krishna; Flick, Ramon; Mandell, Robert B.; Narasimhan, Balaji; Wannemuehler, Michael J.

2014-01-01

Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4+ T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.

Multi-scale biomedical systems: measurement challenges

NASA Astrophysics Data System (ADS)

Summers, R.

2016-11-01

Multi-scale biomedical systems are those that represent interactions in materials, sensors, and systems from a holistic perspective. It is possible to view such multi-scale activity using measurement of spatial scale or time scale, though in this paper only the former is considered. The biomedical application paradigm comprises interactions that range from quantum biological phenomena at scales of 10-12 for one individual to epidemiological studies of disease spread in populations that in a pandemic lead to measurement at a scale of 10+7. It is clear that there are measurement challenges at either end of this spatial scale, but those challenges that relate to the use of new technologies that deal with big data and health service delivery at the point of care are also considered. The measurement challenges lead to the use, in many cases, of model-based measurement and the adoption of virtual engineering. It is these measurement challenges that will be uncovered in this paper.

Online Learning: Research Readings.

ERIC Educational Resources Information Center

Guthrie, Hugh, Ed.

This book comprises an overview and 11 chapters that address issues related to flexible approaches to delivery and online learning in particular. "Overview" (Guthrie) highlights key points drawn from the chapters. "Does Digital Literacy Mean More Than Clicking Your Fingers?" (Candy) discusses the importance of information and…

Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging.

PubMed

Mahdi, Elrashid Saleh; Noor, Azmin Mohd; Sakeena, Mohamed Hameem; Abdullah, Ghassan Z; Abdulkarim, Muthanna F; Sattar, Munavvar Abdul

2011-01-01

Recently there has been a remarkable surge of interest about natural products and their applications in the cosmetic industry. Topical delivery of antioxidants from natural sources is one of the approaches used to reverse signs of skin aging. The aim of this research was to develop a nanoemulsion cream for topical delivery of 30% ethanolic extract derived from local Phyllanthus urinaria (P. urinaria) for skin antiaging. Palm kernel oil esters (PKOEs)-based nanoemulsions were loaded with P. urinaria extract using a spontaneous method and characterized with respect to particle size, zeta potential, and rheological properties. The release profile of the extract was evaluated using in vitro Franz diffusion cells from an artificial membrane and the antioxidant activity of the extract released was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method. Formulation F12 consisted of wt/wt, 0.05% P. urinaria extract, 1% cetyl alcohol, 0.5% glyceryl monostearate, 12% PKOEs, and 27% Tween 80/Span 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and a 59.5% phosphate buffer system at pH 7.4. Formulation F36 was comprised of 0.05% P. urinaria extract, 1% cetyl alcohol, 1% glyceryl monostearate, 14% PKOEs, 28% Tween 80/Span 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and 56% phosphate buffer system at pH 7.4 with shear thinning and thixotropy. The droplet size of F12 and F36 was 30.74 nm and 35.71 nm, respectively, and their nanosizes were confirmed by transmission electron microscopy images. Thereafter, 51.30% and 51.02% of the loaded extract was released from F12 and F36 through an artificial cellulose membrane, scavenging 29.89% and 30.05% of DPPH radical activity, respectively. The P. urinaria extract was successfully incorporated into a PKOEs-based nanoemulsion delivery system. In vitro release of the extract from the formulations showed DPPH radical scavenging activity. These formulations can neutralize reactive oxygen species and counteract oxidative injury induced by ultraviolet radiation and thereby ameliorate skin aging.

An injectable elastin-based gene delivery platform for dose-dependent modulation of angiogenesis and inflammation for critical limb ischemia.

PubMed

Dash, Biraja C; Thomas, Dilip; Monaghan, Michael; Carroll, Oliver; Chen, Xizhe; Woodhouse, Kimberly; O'Brien, Timothy; Pandit, Abhay

2015-10-01

Critical limb ischemia is a major clinical problem. Despite rigorous treatment regimes, there has been only modest success in reducing the rate of amputations in affected patients. Reduced level of blood flow and enhanced inflammation are the two major pathophysiological changes that occur in the ischemic tissue. The objective of this study was to develop a controlled dual gene delivery system capable of delivering therapeutic plasmid eNOS and IL-10 in a temporal manner. In order to deliver multiple therapeutic genes, an elastin-like polypeptide (ELP) based injectable system was designed. The injectable system was comprised of hollow spheres and an in situ-forming gel scaffold of elastin-like polypeptide capable of carrying gene complexes, with an extended manner release profile. In addition, the ELP based injectable system was used to deliver human eNOS and IL-10 therapeutic genes in vivo. A subcutaneous dose response study showed enhanced blood vessel density in the treatment groups of eNOS (20 μg) and IL-10 (10 μg)/eNOS (20 μg) and reduced inflammation with IL-10 (10 μg) alone. Next, we carried out a hind-limb ischemia model comparing the efficacy of the following interventions; Saline; IL-10, eNOS and IL-10/eNOS. The selected dose of eNOS, exhibited enhanced angiogenesis. IL-10 treatment groups showed reduction in the level of inflammatory cells. Furthermore, we demonstrated that eNOS up-regulated major proangiogenic growth factors such as vascular endothelial growth factors, platelet derived growth factor B, and fibroblast growth factor 1, which may explain the mechanism of this approach. These factors help in formation of a stable vascular network. Thus, ELP injectable system mediating non-viral delivery of human IL10-eNOS is a promising therapy towards treating limb ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Introduction strategies raise key questions.

PubMed

Finger, W R; Keller, S

1995-09-01

Key issues that must be considered before a new contraceptive is introduced center on the need for a trained provider to begin or terminate the method, its side effects, duration of use, method's ability to meet users' needs and preferences, and extra training or staff requirements. Logistics and economic issues to consider are identifying a dependable way of effectively supplying commodities, planning extra services needed for the method, and cost of providing the method. Each contraceptive method presents a different side effect pattern and burdens the service delivery setting differently. The strategy developed to introduce or expand the 3-month injectable Depo-Provera (DMPA) can be used for any method. It includes a needs assessment and addresses regulatory issues, service delivery policies and procedures, information and training, evaluation, and other concerns. Viet Nam's needs assessment showed that Norplant should not be introduced until the service delivery system becomes stronger. Any needs assessment for expansion of contraceptive services should cover sexually transmitted disease/HIV issues. A World Health Organization strategy helps officials identify the best method mix for local situations. Introductory strategies must aim to improve the quality of family planning programs and expand choices. Many begin by examining existing data and conducting interviews with policymakers, users, providers, and women's health advocates. Introductory programs for Norplant focus on provider training, adequate counseling and informed consent for users, and ready access to removal. They need a well-prepared service delivery infrastructure. The first phase of the DMPA introductory strategy for the Philippines comprised a social marketing campaign and DMPA introduction at public clinics in 10 pilot areas with strong service delivery. Successful AIDS prevention programs show that people tend to use barrier methods when they are available. USAID is currently studying whether or not women in developing countries will use the female condom.

Bioregenerative Life Support System Research as part of the DLR EDEN Initiative

NASA Astrophysics Data System (ADS)

Bamsey, Matthew; Schubert, Daniel; Zabel, Paul; Poulet, Lucie; Zeidler, Conrad

In 2011, the DLR Institute of Space Systems launched a research initiative called EDEN - Evolution and Design of Environmentally-closed Nutrition-Sources. The research initiative focuses on bioregenerative life support systems, especially greenhouse modules, and technologies for future crewed vehicles. The EDEN initiative comprises several projects with respect to space research, ground testing and spin-offs. In 2014, EDEN’s new laboratory officially opened. This new biological cleanroom laboratory comprises several plant growth chambers incorporating a number of novel controlled environment agriculture technologies. This laboratory will be the nucleus for a variety of plant cultivation experiments within closed environments. The utilized technologies are being advanced using the pull of space technology and include such items as stacked growth systems, PAR-specific LEDs, intracanopy lighting, aeroponic nutrient delivery systems and ion-selective nutrient sensors. The driver of maximizing biomass output per unit volume and energy has much application in future bioregenerative life support systems but can also provide benefit terrestrially. The EDEN laboratory also includes several specially constructed chambers for advancing models addressing the interaction between bioregenerative and physical-chemical life support systems. The EDEN team is presently developing designs for containerized greenhouse modules. One module is planned for deployment to the German Antarctic Station, Neumayer III. The shipping container based system will provide supplementation to the overwintering crew’s diet, provide psychological benefit while at the same time advancing the technology and operational readiness of harsh environment plant production systems. In addition to hardware development, the EDEN team has participated in several early phase designs such as for the ESA Greenhouse Module for Space System and for large-scale vertical farming. These studies often utilize the Institute of Space Systems Concurrent Engineering Facility.

KSC-00pp1601

NASA Image and Video Library

2000-10-23

In the Space Station Processing Facility, a worker is surprised by the camera as she exits the U.S. Lab, Destiny. Inside the lab is the STS-98 crew, which is taking part in Crew Equipment Interface Test activities, becoming familiar with equipment it will be handling during the mission. The crew comprises Commander Ken Cockrell, Pilot Mark Polansky and Mission Specialists Robert Curbeam, Thomas Jones and Marsha Ivins. The mission will be transporting the Lab to the International Space Station with five system racks already installed inside of the module. With delivery of electronics in the lab, electrically powered attitude control for Control Moment Gyroscopes will be activated. The STS-98 launch is scheduled for Jan. 18, 2001

KSC-00pp1600

NASA Image and Video Library

2000-10-23

In the Space Station Processing Facility, workers in the foreground watch and wait while members of the STS-98 crew check out the U.S. Lab, Destiny in the background. The crew comprises Commander Ken Cockrell, Pilot Mark Polansky and Mission Specialists Robert Curbeam, Thomas Jones and Marsha Ivins. They are taking part in Crew Equipment Interface Test activities, becoming familiar with equipment they will be handling during the mission. The mission will be transporting the Lab to the International Space Station with five system racks already installed inside of the module. With delivery of electronics in the lab, electrically powered attitude control for Control Moment Gyroscopes will be activated. The STS-98 launch is scheduled for Jan. 18, 2001

KSC-00pp1598

NASA Image and Video Library

2000-10-23

In the Space Station Processing Facility, members of the STS-98 crew check out components inside the U.S. Lab, Destiny, under the watchful eye of trainers. The crew comprises Commander Ken Cockrell, Pilot Mark Polansky and Mission Specialists Robert Curbeam, Thomas Jones and Marsha Ivins. They are taking part in Crew Equipment Interface Test activities, becoming familiar with equipment they will be handling during the mission. The mission will be transporting the Lab to the International Space Station with five system racks already installed inside of the module. With delivery of electronics in the lab, electrically powered attitude control for Control Moment Gyroscopes will be activated. The STS-98 launch is scheduled for Jan. 18, 2001

KSC-00pp1599

NASA Image and Video Library

2000-10-23

In the Space Station Processing Facility, workers at left watch while members of the STS-98 crew check out equipment inside the U.S. Lab, Destiny (at right). The crew comprises Commander Ken Cockrell, Pilot Mark Polansky and Mission Specialists Robert Curbeam, Thomas Jones and Marsha Ivins. They are taking part in Crew Equipment Interface Test activities, becoming familiar with equipment they will be handling during the mission. The mission will be transporting the Lab to the International Space Station with five system racks already installed inside of the module. With delivery of electronics in the lab, electrically powered attitude control for Control Moment Gyroscopes will be activated. The STS-98 launch is scheduled for Jan. 18, 2001

STS-98 crew members take part in CEIT

NASA Technical Reports Server (NTRS)

2000-01-01

In the Space Station Processing Facility, a worker is surprised by the camera as she exits the U.S. Lab, Destiny. Inside the lab is the STS-98 crew, which is taking part in Crew Equipment Interface Test activities, becoming familiar with equipment it will be handling during the mission. The crew comprises Commander Ken Cockrell, Pilot Mark Polansky and Mission Specialists Robert Curbeam, Thomas Jones and Marsha Ivins. The mission will be transporting the Lab to the International Space Station with five system racks already installed inside of the module. With delivery of electronics in the lab, electrically powered attitude control for Control Moment Gyroscopes will be activated. The STS-98 launch is scheduled for Jan. 18, 2001.

A Palliative Approach to Dialysis Care: A Patient-Centered Transition to the End of Life

PubMed Central

Moss, Alvin H.; Cohen, Lewis M.; Fischer, Michael J.; Germain, Michael J.; Jassal, S. Vanita; Perl, Jeffrey; Weiner, Daniel E.; Mehrotra, Rajnish

2014-01-01

As the importance of providing patient-centered palliative care for patients with advanced illnesses gains attention, standard dialysis delivery may be inconsistent with the goals of care for many patients with ESRD. Many dialysis patients with life expectancy of <1 year may desire a palliative approach to dialysis care, which focuses on aligning patient treatment with patients’ informed preferences. This commentary elucidates what comprises a palliative approach to dialysis care and describes its potential and appropriate use. It also reviews the barriers to integrating such an approach into the current clinical paradigm of care and existing infrastructure and outlines system-level changes needed to accommodate such an approach. PMID:25104274

Effect of Penetration Enhancers on the Percuaneous Delivery of Hormone Replacement Actives.

PubMed

Trimble, John O; Light, Bob

2017-01-01

Transdermal compositions for hormone replacement are comprised of exogenous hormones that are biochemically similar to those produced endogenously by the ovaries or elsewhere in the body. In this work, estradiol, estriol, and testosterone were loaded in transdermal vehicles, prepared using one of three selected penetration enhancer mixtures: Vehicle 1 (olive oil and oleic acid), Vehicle 2 (isopropyl palmitate and lecithin), and Vehicle 3 (isopropyl myristate and lecithin). The influence of penetration enhancers on transdermal delivery was evaluated using Franz-type diffusion cells and Normal Human 3D Model of Epidermal Tissue. Results showed that drug delivery is affected by the penetration enhancer used in the transdermal composition. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Development and piloting of a plan for integrating mental health in primary care in Sehore district, Madhya Pradesh, India

PubMed Central

Shidhaye, Rahul; Shrivastava, Sanjay; Murhar, Vaibhav; Samudre, Sandesh; Ahuja, Shalini; Ramaswamy, Rohit; Patel, Vikram

2016-01-01

Background The large treatment gap for mental disorders in India underlines the need for integration of mental health in primary care. Aims To operationalise the delivery of the World Health Organization Mental Health Gap Action Plan interventions for priority mental disorders and to design an integrated mental healthcare plan (MHCP) comprising packages of care for primary healthcare in one district. Method Mixed methods were used including theory of change workshops, qualitative research to develop the MHCP and piloting of specific packages of care in a single facility. Results The MHCP comprises three enabling packages: programme management, capacity building and community mobilisation; and four service delivery packages: awareness for mental disorders, identification, treatment and recovery. Challenges were encountered in training primary care workers to improve identification and treatment. Conclusions There are a number of challenges to integrating mental health into primary care, which can be addressed through the injection of new resources and collaborative care models. PMID:26447172

Osmotic pellet system comprising osmotic core and in-process amorphized drug in polymer-surfactant layer for controlled delivery of poorly water-soluble drug.

PubMed

Saindane, Nilesh; Vavia, Pradeep

2012-09-01

The aim of the present investigation was to develop controlled porosity osmotic system for poorly water-soluble drug based on drug in polymer-surfactant layer technology. A poorly water-soluble drug, glipizide (GZ), was selected as the model drug. The technology involved core of the pellets containing osmotic agent coated with drug dispersed in polymer and surfactant layer, finally coated with release-retardant layer with pore former. The optimized drug-layer-coated pellets were evaluated for solubility of GZ at different pH conditions and characterized for amorphous nature of the drug by differential scanning calorimetry and X-ray powder diffractometry. The optimized release-retardant layer pellets were evaluated for in vitro drug release at different pH, hydrodynamic, and osmolality conditions. The optimized drug layer showed improvement in solubility (10 times in pH 1.2, 11 times in pH 4.5, and 21 times in pH 6.8), whereas pellets coated with cellulose acetate (15.0%, w/w, weight gain) with pore former triethyl citrate (10.0%, w/w, of polymer) demonstrated zero-order drug release for 24 h at different pH conditions; moreover, retardation of drug release was observed with increment of osmolality. This system could be a platform technology for controlled delivery of poorly water-soluble drugs. Copyright © 2012 Wiley Periodicals, Inc.

In vivo determination of the time and location of mucoadhesive drug delivery systems disintegration in the gastrointestinal tract.

PubMed

Kremser, Christian; Albrecht, Karin; Greindl, Melanie; Wolf, Christian; Debbage, Paul; Bernkop-Schnürch, Andreas

2008-06-01

The objective of this study was to use magnetic resonance imaging (MRI) to detect the time when and the location at which orally delivered mucoadhesive drugs are released. Drug delivery systems comprising tablets or capsules containing a mucoadhesive polymer were designed to deliver the polymer to the intestine in dry powder form. Dry Gd-DTPA [diethylenetriaminepentaacetic acid gadolinium(III) dihydrogen salt hydrate] powder was added to the mucoadhesive polymer, resulting in a susceptibility artifact that allows tracking of the application forms before their disintegration and that gives a strong positive signal on disintegration. Experiments were performed with rats using T(1)-weighted spin-echo imaging on a standard 1.5-T MRI system. The susceptibility artifact produced by the dry Gd-DTPA powder in tablets or capsules was clearly visible within the stomach of the rats and could be followed during movement towards the intestine. Upon disintegration, a strong positive signal was unambiguously observed. The time between ingestion and observation of a positive signal was significantly different for different application forms. Quantification of the remaining mucoadhesive polymer in the intestine 3 h after observed release showed significant differences in mucoadhesive effectiveness. MRI allows detection of the exact time of release of the mucoadhesive polymer in vivo, which is a prerequisite for a reliable quantitative comparison between different application forms.

Intracellular co-delivery of Sr ion and phenamil drug through mesoporous bioglass nanocarriers synergizes BMP signaling and tissue mineralization.

PubMed

Lee, Jung-Hwan; Mandakhbayar, Nandin; El-Fiqi, Ahmed; Kim, Hae-Won

2017-09-15

Inducing differentiation and maturation of resident multipotent stem cells (MSCs) is an important strategy to regenerate hard tissues in mal-calcification conditions. Here we explore a co-delivery approach of therapeutic molecules comprised of ion and drug through a mesoporous bioglass nanoparticle (MBN) for this purpose. Recently, MBN has offered unique potential as a nanocarrier for hard tissues, in terms of high mesoporosity, bone bioactivity (and possibly degradability), tunable delivery of biomolecules, and ionic modification. Herein Sr ion is structurally doped to MBN while drug Phenamil is externally loaded as a small molecule activator of BMP signaling, for the stimulation of osteo/odontogenesis and mineralization of human MSCs derived from dental pulp. The Sr-doped MBN (85Si:10Ca:5Sr) sol-gel processed presents a high mesoporosity with a pore size of ∼6nm. In particular, Sr ion is released slowly at a daily rate of ∼3ppm per mg nanoparticles for up to 7days, a level therapeutically effective for cellular stimulation. The Sr-MBN is internalized to most MSCs via an ATP dependent macropinocytosis within hours, increasing the intracellular levels of Sr, Ca and Si ions. Phenamil is loaded maximally ∼30% into Sr-MBN and then released slowly for up to 7days. The co-delivered molecules (Sr ion and Phenamil drug) have profound effects on the differentiation and maturation of cells, i.e., significantly enhancing expression of osteo/odontogenic genes, alkaline phosphatase activity, and mineralization of cells. Of note, the stimulation is a result of a synergism of Sr and Phenamil, through a Trb3-dependent BMP signaling pathway. This biological synergism is further evidenced in vivo in a mal-calcification condition involving an extracted tooth implantation in dorsal subcutaneous tissues of rats. Six weeks post operation evidences the osseous-dentinal hard tissue formation, which is significantly stimulated by the Sr/Phenamil delivery, based on histomorphometric and micro-computed tomographic analyses. The bioactive nanoparticles releasing both Sr ion and Phenamil drug are considered to be a promising therapeutic nanocarrier platform for hard tissue regeneration. Furthermore, this novel ion/drug co-delivery concept through nanoparticles can be extensively used for other tissues that require different therapeutic treatment. This study reports a novel design concept in inorganic nanoparticle delivery system for hard tissues - the co-delivery of therapeutic molecules comprised of ion (Sr) and drug (Phenamil) through a unique nanoparticle of mesoporous bioactive glass (MBN). The physico-chemical and biological properties of MBN enabled an effective loading of both therapeutic molecules and a subsequently sustained/controlled release. The co-delivered Sr and Phenamil demonstrated significant stimulation of adult stem cell differentiation in vitro and osseous/dentinal regeneration in vivo, through BMP signaling pathways. We consider the current combination of Sr ion with Phenamil is suited for the osteo/odontogenesis of stem cells for hard tissue regeneration, and further, this ion/drug co-delivery concept can extend the applications to other areas that require specific cellular and tissue functions. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Method and apparatus for determining two-phase flow in rock fracture

DOEpatents

Persoff, Peter; Pruess, Karsten; Myer, Larry

1994-01-01

An improved method and apparatus as disclosed for measuring the permeability of multiple phases through a rock fracture. The improvement in the method comprises delivering the respective phases through manifolds to uniformly deliver and collect the respective phases to and from opposite edges of the rock fracture in a distributed manner across the edge of the fracture. The improved apparatus comprises first and second manifolds comprising bores extending within porous blocks parallel to the rock fracture for distributing and collecting the wetting phase to and from surfaces of the porous blocks, which respectively face the opposite edges of the rock fracture. The improved apparatus further comprises other manifolds in the form of plenums located adjacent the respective porous blocks for uniform delivery of the non-wetting phase to parallel grooves disposed on the respective surfaces of the porous blocks facing the opposite edges of the rock fracture and generally perpendicular to the rock fracture.

Methodological approaches of health technology assessment.

PubMed

Goodman, C S; Ahn, R

1999-12-01

In this era of evolving health care systems throughout the world, technology remains the substance of health care. Medical informatics comprises a growing contribution to the technologies used in the delivery and management of health care. Diverse, evolving technologies include artificial neural networks, computer-assisted surgery, computer-based patient records, hospital information systems, and more. Decision-makers increasingly demand well-founded information to determine whether or how to develop these technologies, allow them on the market, acquire them, use them, pay for their use, and more. The development and wider use of health technology assessment (HTA) reflects this demand. While HTA offers systematic, well-founded approaches for determining the value of medical informatics technologies, HTA must continue to adapt and refine its methods in response to these evolving technologies. This paper provides a basic overview of HTA principles and methods.

The invisible extension cord

NASA Astrophysics Data System (ADS)

Gunn, Stanley V.

1998-01-01

The term, ``power beaming'', creates an image of a beam of focused electromagnetic radiation, possessing good transmission characteristics and sufficient intensity to effect the delivery of meaningful amounts of power to a designated receiver. High power, free-electron lasers are well suited for long range transmission of their laser beam to designated space receivers because their selective near infrared wave length can be adjusted to match the absorption characteristics of the receiver's photo voltaic cells. The typical system envisioned is comprised of a 200 kw free electron laser, possessing an over-all efficiency of 10%, and an optical beam director system equipped with appropriate tracking and atmospheric compensation capabilities. Such an installation located at four to five appropriate locations around the earth could provide remarkable benefits to the projected power demands for transfer and maneuvering into orbit and for operating future fleets of satellites.

Apparatus for producing nanoscale ceramic powders

DOEpatents

Helble, Joseph J.; Moniz, Gary A.; Morse, Theodore F.

1997-02-04

An apparatus provides high temperature and short residence time conditions for the production of nanoscale ceramic powders. The apparatus includes a confinement structure having a multiple inclined surfaces for confining flame located between the surfaces so as to define a flame zone. A burner system employs one or more burners to provide flame to the flame zone. Each burner is located in the flame zone in close proximity to at least one of the inclined surfaces. A delivery system disposed adjacent the flame zone delivers an aerosol, comprising an organic or carbonaceous carrier material and a ceramic precursor, to the flame zone to expose the aerosol to a temperature sufficient to induce combustion of the carrier material and vaporization and nucleation, or diffusion and oxidation, of the ceramic precursor to form pure, crystalline, narrow size distribution, nanophase ceramic particles.

Apparatus for producing nanoscale ceramic powders

DOEpatents

Helble, Joseph J.; Moniz, Gary A.; Morse, Theodore F.

1995-09-05

An apparatus provides high temperature and short residence time conditions for the production of nanoscale ceramic powders. The apparatus includes a confinement structure having a multiple inclined surfaces for confining flame located between the surfaces so as to define a flame zone. A burner system employs one or more burners to provide flame to the flame zone. Each burner is located in the flame zone in close proximity to at least one of the inclined surfaces. A delivery system disposed adjacent the flame zone delivers an aerosol, comprising an organic or carbonaceous carrier material and a ceramic precursor, to the flame zone to expose the aerosol to a temperature sufficient to induce combustion of the carrier material and vaporization and nucleation, or diffusion and oxidation, of the ceramic precursor to form pure, crystalline, narrow size distribution, nanophase ceramic particles.

Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system

PubMed Central

Chen, Zhi-Qiang; Liu, Ying; Zhao, Ji-Hui; Wang, Lan; Feng, Nian-Ping

2012-01-01

Background Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin. Methods A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats. Results The prototype formulation of S-SMEDDS comprised Maisine™ 35-1:Cremophor® EL:Transcutol® P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS. Conclusion The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin. PMID:22403491

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

PubMed

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

2008-12-01

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

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

PubMed

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

2016-01-04

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

Supercapacitor Electrolyte Solvents with Liquid Range Below -80 C

NASA Technical Reports Server (NTRS)

Brandon, Erik; Smart, Marshall; West, William

2010-01-01

A previous NASA Tech Brief ["Low-Temperature Supercapacitors" (NPO-44386) NASA Tech Briefs, Vol. 32, No 7 (July 2008), page 32] detailed ongoing efforts to develop non-aqueous supercapacitor electrolytes capable of supporting operation at temperatures below commercially available cells (which are typically limited to charging and discharging at > or equal to -40 C). These electrolyte systems may enable energy storage and power delivery for systems operating in extreme environments, such as those encountered in the Polar regions on Earth or in the exploration of space. Supercapacitors using these electrolytes may also offer improved power delivery performance at moderately low temperatures (e.g. -40 to 0 C) relative to currently available cells, offering improved cold-cranking and cold-weather acceleration capabilities for electrical or hybrid vehicles. Supercapacitors store charge at the electrochemical double-layer, formed at the interface between a high surface area electrode material and a liquid electrolyte. The current approach to extending the low-temperature limit of the electrolyte focuses on using binary solvent systems comprising a high-dielectric-constant component (such as acetonitrile) in conjunction with a low-melting-point co-solvent (such as organic formates, esters, and ethers) to depress the freezing point of the system, while maintaining sufficient solubility of the salt. Recent efforts in this area have led to the identification of an electrolyte solvent formulation with a freezing point of -85.7 C, which is achieved by using a 1:1 by volume ratio of acetonitrile to 1,3-dioxolane

Intramuscular delivery of heterodimeric IL-15 DNA in macaques produces systemic levels of bioactive cytokine inducing proliferation of NK and T cells.

PubMed

Bergamaschi, C; Kulkarni, V; Rosati, M; Alicea, C; Jalah, R; Chen, S; Bear, J; Sardesai, N Y; Valentin, A; Felber, B K; Pavlakis, G N

2015-01-01

Interleukin-15 (IL-15) is a common γ-chain cytokine that has a significant role in the activation and proliferation of T and NK cells and holds great potential in fighting infection and cancer. We have previously shown that bioactive IL-15 in vivo comprises a complex of the IL-15 chain with the soluble or cell-associated IL-15 receptor alpha (IL-15Rα) chain, which together form the IL-15 heterodimer. We have generated DNA vectors expressing the heterodimeric IL-15 by optimizing mRNA expression and protein trafficking. Repeated administration of these DNA plasmids by intramuscular injection followed by in vivo electroporation in rhesus macaques resulted in sustained high levels of IL-15 in plasma, with no significant toxicity. Administration of DNAs expressing heterodimeric IL-15 also resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. Heterodimeric IL-15 led to preferential expansion of CD8(+)NK cells, all memory CD8(+) T-cell subsets and effector memory CD4(+) T cells. Expression of heterodimeric IL-15 by DNA delivery to the muscle is an efficient procedure to obtain high systemic levels of bioactive cytokine, without the toxicity linked to the high transient cytokine peak associated with protein injection.

The Role of Polydimethylsiloxane in the Molecular Structure of Silica Xerogels Intended for Drug Carriers

PubMed Central

Czarnobaj, Katarzyna

2015-01-01

The aim of this study was to prepare and examine polymer/oxide xerogels with metronidazole (MT) as delivery systems for the local application of a drug to a bone. The nanoporous SiO2-CaO and PDMS-modified SiO2-CaO xerogel materials with different amounts of the polymer, polydimethylsiloxane (PDMS), were prepared by the sol-gel method. Characterization assays comprised the analysis of the composite materials by using Fourier transform infrared spectroscopy (FTIR), determining the specific surface area of solids (BET), using X-ray powder diffraction (XRD) and scanning electron microscope (SEM) techniques, and further monitoring in the ultraviolet and visible light regions (UV-Vis) of the in vitro release of the drug (metronidazole) over time. According to these results, the bioactive character and chemical stability of PDMS-modified silica xerogels have been proven. The release of MT from xerogels was strongly correlated with the composition of the matrix. In comparison with the pure oxide matrix, PDMS-modified matrices accelerated the release of the drug through its bigger pores, and additionally, on account of weaker interactions with the drug. The obtained results for the xerogel composites suggest that the metronidazole-loaded xerogels could be promising candidates for formulations in local delivery systems particularly to bone. PMID:26839836

KSC-00pp1732

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, is lifted toward the payload changeout room (PCR). The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure that supports payload delivery at the pad and subsequent vertical installation in the orbiter payload bay. Attached to the canister are the red umbilical lines that maintain the controlled environment inside. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC00pp1732

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, is lifted toward the payload changeout room (PCR). The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure that supports payload delivery at the pad and subsequent vertical installation in the orbiter payload bay. Attached to the canister are the red umbilical lines that maintain the controlled environment inside. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

Defining the scope of systems of care: an ecological perspective.

PubMed

Cook, James R; Kilmer, Ryan P

2010-02-01

The definition of a system of care (SOC) can guide those intending to develop and sustain SOCs. Hodges, Ferreira, Israel, and Mazza [Hodges, S., Ferreira, K., Israel, N., & Mazza, J. (in press). Systems of care, featherless bipeds, and the measure of all things. Evaluation and Program Planning] have emphasized contexts in which services are provided to families, plus the adaptive, dynamic, complex nature of systems and multiple components that comprise SOCs. However, two areas need additional clarification: (1) the nature of the "system" of concern in a "system of care," and how it should differ from a "service delivery system"; and (2) the degree to which intended, or desired, outcomes of a SOC extend beyond increased access to "necessary" services and supports. These prime issues in the conceptualization of SOCs are addressed, drawing on ecological theory to underscore the need for broader systems--including factors in the proximal and distal contexts of children and families--to be engaged in the process of promoting well-being and helping children and families function and participate fully in their communities. A revised definition is proposed, with implications for the implementation of SOCs.

Thiomers: a new generation of mucoadhesive polymers.

PubMed

Bernkop-Schnürch, Andreas

2005-11-03

Thiolated polymers or designated thiomers are mucoadhesive basis polymers, which display thiol bearing side chains. Based on thiol/disulfide exchange reactions and/or a simple oxidation process disulfide bonds are formed between such polymers and cysteine-rich subdomains of mucus glycoproteins building up the mucus gel layer. Thiomers mimic therefore the natural mechanism of secreted mucus glycoproteins, which are also covalently anchored in the mucus layer by the formation of disulfide bonds-the bridging structure most commonly encountered in biological systems. So far the cationic thiomers chitosan-cysteine, chitosan-thiobutylamidine as well as chitosan-thioglycolic acid and the anionic thiomers poly(acylic acid)-cysteine, poly(acrylic acid)-cysteamine, carboxy-methylcellulose-cysteine and alginate-cysteine have been generated. Due to the immobilization of thiol groups on mucoadhesive basis polymers, their mucoadhesive properties are 2- up to 140-fold improved. The higher efficacy of this new generation of mucoadhesive polymers in comparison to the corresponding unmodified mucoadhesive basis polymers could be verified via various in vivo studies on various mucosal membranes in different animal species and in humans. The development of first commercial available products comprising thiomers is in progress. Within this review an overview of the mechanism of adhesion and the design of thiomers as well as delivery systems comprising thiomers and their in vivo performance is provided.

Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

PubMed

Boakye, Cedar H A; Patel, Ketan; Patel, Apurva R; Faria, Henrique A M; Zucolotto, Valtencir; Safe, Stephen; Singh, Mandip

2016-10-01

The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ.

Polymeric biomaterials for nerve regeneration applications: From promoting cellular organization to the delivery of bioactive molecules

NASA Astrophysics Data System (ADS)

Delgado-Rivera, Roberto L.

Thousands of new cases of injury to the central nervous system (CNS) occur each year in the USA and all over the world. However, despite recent advances, at present there is no cure for the resulting paraplegia or quadriplegia. This research is directed towards engineering biomaterial platforms to promote cellular organization at the surface of polymer scaffolds that will be conducive to proper regeneration of injured CNS. In addition, the formulation of a delivery system for neuroactive molecules using polymer-based materials will be evaluated to establish its potential to treat CNS disorders. Initial studies involved the chemical modification of an electrospun nonwoven matrix of nanofibers with fibroblast growth factor 2 (FGF-2). Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, that FGF-2 modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of damaged tissue following CNS injury or disease. Subsequent research efforts focused on a novel micropatterning technique called microscale plasma-initiated patterning (microPIP). This patterning method uses a polydimethylsiloxane (PDMS) stamp to selectively protect regions of an underlying substrate from oxygen plasma treatment resulting in hydrophobic and hydrophilic regions. FGF-2 and laminin-1 were applied to an electrospun polyamide nanofibrillar matrix following plasma treatment. In this work it, was possible to demonstrate that textured surfaces, such as nanofibrillar scaffolds, can be micropatterned to provide external chemical cues for cellular organization. Finally, a microsphere system capable of encapsulating proteins while minimizing the mechanisms of protein degradation and providing a controlled release was investigated. Microspheres were comprised of a salicylic-acid based poly(anhydride-ester) (PAE), a biodegradable polymer that incorporates salicylic acid into the polymer backbone (PolyAspirin). The use of microspheres formulated from PolyAspirin as a delivery vehicle can be advantageous due its ability of performing a dual delivery; biomolecule (protein) and drug. By combining these two properties, it will be possible to release neurotrophic factors to induce a biological response while mitigating inflammatory pathways due to the localized delivery of salicylic acid.

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

A mechanics approach to the study of pressure sensitive adhesives and human skin for transdermal drug delivery applications

NASA Astrophysics Data System (ADS)

Taub, Marc Barry

Transdermal drug delivery is an alternative approach to the systemic delivery of pharmaceuticals where drugs are administered through the skin and absorbed percutaneously. This method of delivery offers several advantages over more traditional routes; most notably, the avoidance of the fast-pass metabolism of the liver and gut, the ability to offer controlled release rates, and the possibility for novel devices. Pressure sensitive adhesives (PSAs) are used to bond transdermal drug delivery devices to the skin because of their good initial and long-term adhesion, clean removability, and skin and drug compatibility. However, an understanding of the mechanics of adhesion to the dermal layer, together with quantitative and reproducible test methods for measuring adhesion, have been lacking. This study utilizes a mechanics-based approach to quantify the interfacial adhesion of PSAs bonded to selected substrates, including human dermal tissue. The delamination of PSA layers is associated with cavitation in the PSA followed by the formation of an extensive cohesive zone behind the debond tip. A quantitative metrology was developed to assess the adhesion and delamination of PSAs, such that it could be possible to easily distinguish between the adhesive characteristics of different PSA compositions and to provide a quantitative basis from which the reliability of adhesive layers bonded to substrates could be studied. A mechanics-based model was also developed to predict debonding in terms of the relevant energy dissipation mechanisms active during this process. As failure of transdermal devices may occur cohesively within the PSA layer, adhesively at the interface between the PSA and the skin, or cohesively between the corneocytes that comprise the outermost layer of the skin, it was also necessary to explore the mechanical and fracture properties of human skin. The out-of-plane delamination of corneocytes was studied by determining the strain energy release rate during debonding of cantilever-beam specimens containing thin layers of human dermal tissue at their midline. Finally, the interfacial adhesion of PSAs bonded to human skin was studied and the mechanics model that was developed for PSA failure was extended to provide the capability for in vivo reliability predictions for transdermal systems bonded to human skin.

77 FR 38769 - 97th Annual Meeting of the National Conference on Weights and Measures

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

... testing equipment that comprise the regulatory control of commercial weighing and measuring devices. The... specifications to recognize current marketing practices of offering pre or post delivery discounts on fuel prices... proposal would allow device manufacturers greater flexibility in the design and operation of customer...

Summer Literacy Unit for Elementary Students

ERIC Educational Resources Information Center

Bahrenfuss, Diane M.; Weih, Timothy G.

2016-01-01

This paper contains an instructional unit designed for teaching elementary students who struggle with reading comprehension. The literacy strategies that comprise the unit are grounded in the relevant research-based literature that is cited and referenced in the paper. Methods for instructional delivery are included as well as detailed lessons.…

Educating Homeless Children: Issues and Answers. Fastback 313.

ERIC Educational Resources Information Center

Stronge, James H.; Tenhouse, Cheri

This publication summarizes issues relating to the education of homeless children and youth and reviews programs that are effective in the delivery of educational services to this population. The report is comprised of five sections. The first section, "Introduction," surveys factors contributing to homelessness and indicates the special…

Targeting of drugs and nanoparticles to tumors

PubMed Central

Bhatia, Sangeeta N.; Sailor, Michael J.

2010-01-01

The various types of cells that comprise the tumor mass all carry molecular markers that are not expressed or are expressed at much lower levels in normal cells. These differentially expressed molecules can be used as docking sites to concentrate drug conjugates and nanoparticles at tumors. Specific markers in tumor vessels are particularly well suited for targeting because molecules at the surface of blood vessels are readily accessible to circulating compounds. The increased concentration of a drug in the site of disease made possible by targeted delivery can be used to increase efficacy, reduce side effects, or achieve some of both. We review the recent advances in this delivery approach with a focus on the use of molecular markers of tumor vasculature as the primary target and nanoparticles as the delivery vehicle. PMID:20231381

Participatory video-assisted evaluation of truck drivers' work outside cab: deliveries in two types of transport.

PubMed

Reiman, Arto; Pekkala, Janne; Väyrynen, Seppo; Putkonen, Ari; Forsman, Mikael

2014-01-01

The aim of this study was to identify risks and ergonomics discomfort during work of local and short haul delivery truck drivers outside a cab. The study used a video- and computer-based method (VIDAR). VIDAR is a participatory method identifying demanding work situations and their potential risks. The drivers' work was videoed and analysed by subjects and ergonomists. Delivery truck drivers should not be perceived as one group with equal risks because there were significant differences between the 2 types of transportation and specific types of risks. VIDAR produces visual material for risk management processes. VIDAR as a participatory approach stimulates active discussion about work-related risks and discomfort, and about possibilities for improvement. VIDAR may be also applied to work which comprises different working environments.

Reversible Stabilization of Vesicles: Redox-Responsive Polymer Nanocontainers for Intracellular Delivery.

PubMed

de Vries, Wilke C; Grill, David; Tesch, Matthias; Ricker, Andrea; Nüsse, Harald; Klingauf, Jürgen; Studer, Armido; Gerke, Volker; Ravoo, Bart Jan

2017-08-01

We present the self-assembly of redox-responsive polymer nanocontainers comprising a cyclodextrin vesicle core and a thin reductively cleavable polymer shell anchored via host-guest recognition on the vesicle surface. The nanocontainers are of uniform size, show high stability, and selectively respond to a mild reductive trigger as revealed by dynamic light scattering, transmission electron microscopy, atomic force microscopy, a quantitative thiol assay, and fluorescence spectroscopy. Live cell imaging experiments demonstrate a specific redox-responsive release and cytoplasmic delivery of encapsulated hydrophilic payloads, such as the pH-probe pyranine, and the fungal toxin phalloidin. Our results show the high potential of these stimulus-responsive nanocontainers for cell biological applications requiring a controlled delivery. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Perinatal staff perceptions of safety and quality in their service.

PubMed

Sinni, Suzanne V; Wallace, Euan M; Cross, Wendy M

2014-11-28

Ensuring safe and appropriate service delivery is central to a high quality maternity service. With this in mind, over recent years much attention has been given to the development of evidence-based clinical guidelines, staff education and risk reporting systems. Less attention has been given to assessing staff perceptions of a service's safety and quality and what factors may influence that. In this study we set out to assess staff perceptions of safety and quality of a maternity service and to explore potential influences on service safety. The study was undertaken within a new low risk metropolitan maternity service in Victoria, Australia with a staffing profile comprising midwives (including students), neonatal nurses, specialist obstetricians, junior medical staff and clerical staff. In depth open-ended interviews using a semi-structured questionnaire were conducted with 23 staff involved in the delivery of perinatal care, including doctors, midwives, nurses, nursing and midwifery students, and clerical staff. Data were analyzed using naturalistic interpretive inquiry to identify emergent themes. Staff unanimously reported that there were robust systems and processes in place to maintain safety and quality. Three major themes were apparent: (1) clinical governance, (2) dominance of midwives, (3) inter-professional relationships. Overall, there was a strong sense that, at least in this midwifery-led service, midwives had the greatest opportunity to be an influence, both positively and negatively, on the safe delivery of perinatal care. The importance of understanding team dynamics, particularly mutual respect, trust and staff cohesion, were identified as key issues for potential future service improvement. Senior staff, particularly midwives and neonatal nurses, play central roles in shaping team behaviors and attitudes that may affect the safety and quality of service delivery. We suggest that strategies targeting senior staff to enhance their performance in their roles, particularly in the training and teamwork role-modeling of the transitory junior workforce, are important for the development and maintenance of a high quality and safe maternity service.

[Identification of difficulties at the beginning of breastfeeding by means of protocol application].

PubMed

Carvalhaes, Maria Antonieta de Barros Leite; Corrêa, Cláudia Regina Hostin

2003-01-01

To assess a group of mothers/newborns with the necessity of special support at the beginning of breastfeeding by means of protocol application recommended by UNICEF and to verify assisting practices associated with difficulties of breastfeeding.\\par In this descriptive study, the sample comprised 50 mother/newborn pairs randomly selected in a maternity where low risk deliveries are cared by SUS (Brazilian Unified Health System). The breastfeeding observation protocol was used to record the behavior of each pair, including the frequency of negative behavior regarding breastfeeding. Next, each aspect was scored as good, regular or poor. The association between negative scores and particular assisting practices was also investigated. A critical level of p < 0.05 was used.\\par The frequency of pairs presenting evidence of severe problems (poor score) at the beginning of breastfeeding ranged from 2% to 22% according to the aspects assessed. The most frequently observed difficulties were mother and infant's bad positioning during breastfeeding and inappropriate mother/newborn interaction. These problems were significantly more frequent after surgical deliveries (p < 0.05). Milk formula and/or glucose solution was also associated with the worst scores in some breastfeeding aspects. \\par The protocol application to observe and evaluate breastfeeding identified a high prevalence of mothers/newborn pairs with difficulties to begin breastfeeding, especially when the delivery was surgically performed and when the newborn was offered supplementary liquids.

Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

PubMed Central

2017-01-01

Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld. PMID:29211023

Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

PubMed

Hahn, Ulrich

2017-12-06

Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers-in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

Lysimeter apparatus

DOEpatents

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

2005-09-06

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

The free delivery and caesarean policy in Morocco: how much do households still pay?

PubMed

Boukhalfa, C; Abouchadi, S; Cunden, N; Witter, S

2016-02-01

The Free Deliveries and Caesarean Policy (FDCP) entitles all women in Morocco to deliver free of charge within public hospitals. This study assesses the policy's effectiveness by analysing household expenditures related to childbirth, by delivery type and quintile. Structured exit survey of 973 women in six provinces at five provincial hospitals, two regional hospitals, two university hospitals and three primary health centres with maternity units. Households reported spending a median of US$ 59 in total for costs inside and outside of hospitals. Women requiring caesareans payed more than women with uncomplicated deliveries (P < 0.0001). The median cost was US$45 for a uncomplicated delivery, US$50 for a complicated delivery and US$65 for a caesarean section. The prescription given upon exiting the hospital comprised 62% of the total costs. Eighty-eight per cent of women from the poorest quintiles faced catastrophic expenditures. The women's perception of their hospital stay and the FDCP policy was overwhelmingly positive, but differences were noted at the various sites. The policy has been largely but not fully effective in removing financial barriers for delivery care in Morocco. More progress should also be made on increasing awareness of the policy and on easing the financial burden, which is still borne by households with lower incomes. © 2015 John Wiley & Sons Ltd.

Policy challenges for the pediatric rheumatology workforce: Part II. Health care system delivery and workforce supply

PubMed Central

2011-01-01

The United States pediatric population with chronic health conditions is expanding. Currently, this demographic comprises 12-18% of the American child and youth population. Affected children often receive fragmented, uncoordinated care. Overall, the American health care delivery system produces modest outcomes for this population. Poor, uninsured and minority children may be at increased risk for inferior coordination of services. Further, the United States health care delivery system is primarily organized for the diagnosis and treatment of acute conditions. For pediatric patients with chronic health conditions, the typical acute problem-oriented visit actually serves as a barrier to care. The biomedical model of patient education prevails, characterized by unilateral transfer of medical information. However, the evidence basis for improvement in disease outcomes supports the use of the chronic care model, initially proposed by Dr. Edward Wagner. Six inter-related elements distinguish the success of the chronic care model, which include self-management support and care coordination by a prepared, proactive team. United States health care lacks a coherent policy direction for the management of high cost chronic conditions, including rheumatic diseases. A fundamental restructure of United States health care delivery must urgently occur which places the patient at the center of care. For the pediatric rheumatology workforce, reimbursement policies and the actions of health plans and insurers are consistent barriers to chronic disease improvement. United States reimbursement policy and overall fragmentation of health care services pose specific challenges for widespread implementation of the chronic care model. Team-based multidisciplinary care, care coordination and self-management are integral to improve outcomes. Pediatric rheumatology demand in the United States far exceeds available workforce supply. This article reviews the career choice decision-making process at each medical trainee level to determine best recruitment strategies. Educational debt is an unexpectedly minor determinant for pediatric residents and subspecialty fellows. A two-year fellowship training option may retain the mandatory scholarship component and attract an increasing number of candidate trainees. Diversity, work-life balance, scheduling flexibility to accommodate part-time employment, and reform of conditions for academic promotion all need to be addressed to ensure future growth of the pediatric rheumatology workforce. PMID:21843335

Policy challenges for the pediatric rheumatology workforce: Part II. Health care system delivery and workforce supply.

PubMed

Henrickson, Michael

2011-01-01

The United States pediatric population with chronic health conditions is expanding. Currently, this demographic comprises 12-18% of the American child and youth population. Affected children often receive fragmented, uncoordinated care. Overall, the American health care delivery system produces modest outcomes for this population. Poor, uninsured and minority children may be at increased risk for inferior coordination of services. Further, the United States health care delivery system is primarily organized for the diagnosis and treatment of acute conditions. For pediatric patients with chronic health conditions, the typical acute problem-oriented visit actually serves as a barrier to care. The biomedical model of patient education prevails, characterized by unilateral transfer of medical information. However, the evidence basis for improvement in disease outcomes supports the use of the chronic care model, initially proposed by Dr. Edward Wagner. Six inter-related elements distinguish the success of the chronic care model, which include self-management support and care coordination by a prepared, proactive team. United States health care lacks a coherent policy direction for the management of high cost chronic conditions, including rheumatic diseases. A fundamental restructure of United States health care delivery must urgently occur which places the patient at the center of care. For the pediatric rheumatology workforce, reimbursement policies and the actions of health plans and insurers are consistent barriers to chronic disease improvement. United States reimbursement policy and overall fragmentation of health care services pose specific challenges for widespread implementation of the chronic care model. Team-based multidisciplinary care, care coordination and self-management are integral to improve outcomes. Pediatric rheumatology demand in the United States far exceeds available workforce supply. This article reviews the career choice decision-making process at each medical trainee level to determine best recruitment strategies. Educational debt is an unexpectedly minor determinant for pediatric residents and subspecialty fellows. A two-year fellowship training option may retain the mandatory scholarship component and attract an increasing number of candidate trainees. Diversity, work-life balance, scheduling flexibility to accommodate part-time employment, and reform of conditions for academic promotion all need to be addressed to ensure future growth of the pediatric rheumatology workforce.

Wireless energizing system for an automated implantable sensor

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

Swain, Biswaranjan; Nayak, Praveen P.; Kar, Durga P.

The wireless drive of an automated implantable electronic sensor has been explored for health monitoring applications. The proposed system comprises of an automated biomedical sensing system which is energized through resonant inductive coupling. The implantable sensor unit is able to monitor the body temperature parameter and sends back the corresponding telemetry data wirelessly to the data recoding unit. It has been observed that the wireless power delivery system is capable of energizing the automated biomedical implantable electronic sensor placed over a distance of 3 cm from the power transmitter with an energy transfer efficiency of 26% at the operating resonantmore » frequency of 562 kHz. This proposed method ensures real-time monitoring of different human body temperatures around the clock. The monitored temperature data have been compared with a calibrated temperature measurement system to ascertain the accuracy of the proposed system. The investigated technique can also be useful for monitoring other body parameters such as blood pressure, bladder pressure, and physiological signals of the patient in vivo using various implantable sensors.« less

Racial and ethnic differences in the risk of postpartum venous thromboembolism: a population-based, case-control study.

PubMed

Blondon, M; Harrington, L B; Righini, M; Boehlen, F; Bounameaux, H; Smith, N L

2014-12-01

Venous thromboembolism (VTE) is a major contributor of maternal morbidity and mortality. Whether maternal race/ethnicity is associated with the risk of postpartum VTE remains unclear. We conducted a population-based, case-control study in Washington State, from 1987 through 2011. Cases comprised all women with selected International Classification of Diseases, Ninth Edition, Clinical Modification codes for hospitalized VTE within 3 months post-delivery. Controls were randomly selected postpartum women who did not experience a VTE. Characteristics of women and their deliveries were abstracted from birth certificates. Using logistic regression models, we compared the risk of postpartum VTE in black, Asian, and Hispanic women with that in non-Hispanic white women, after adjustment for maternal characteristics (age, body mass index, parity, education), pregnancy complications, and delivery methods. Our study comprised 688 cases and 10 246 controls. Among controls, the mean age and body mass index were 27.5 years and 26.3 kg m(-2) , respectively. Compared with white women, black and Asian women had a greater and lower risk of postpartum VTE (adjusted odds ratio [OR] 1.50, 95% confidence interval [CI] 1.10-2.04 and OR 0.67, 95%CI 0.48-0.94, respectively). A lower risk was present in Hispanic women (adjusted OR 0.80, 95% CI 0.61-1.06) but was not statistically significant. In subgroup analyses, we observed an increased risk for black compared with white women among women who delivered via cesarean section (OR 2.03, 95% CI 1.34-3.07) but not among vaginal deliveries (OR 1.03, 95% CI 0.61-1.74). Maternal race/ethnicity is associated with the risk of postpartum VTE, independently of other risk factors, and should be considered when assessing the use of thromboprophylaxis after delivery. © 2014 International Society on Thrombosis and Haemostasis.

A palliative approach to dialysis care: a patient-centered transition to the end of life.

PubMed

Grubbs, Vanessa; Moss, Alvin H; Cohen, Lewis M; Fischer, Michael J; Germain, Michael J; Jassal, S Vanita; Perl, Jeffrey; Weiner, Daniel E; Mehrotra, Rajnish

2014-12-05

As the importance of providing patient-centered palliative care for patients with advanced illnesses gains attention, standard dialysis delivery may be inconsistent with the goals of care for many patients with ESRD. Many dialysis patients with life expectancy of <1 year may desire a palliative approach to dialysis care, which focuses on aligning patient treatment with patients' informed preferences. This commentary elucidates what comprises a palliative approach to dialysis care and describes its potential and appropriate use. It also reviews the barriers to integrating such an approach into the current clinical paradigm of care and existing infrastructure and outlines system-level changes needed to accommodate such an approach. Copyright © 2014 by the American Society of Nephrology.

Electromagnetic field triggered drug and chemical delivery via liposomes

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

Liburdy, R.P.

1993-03-02

The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release the chemical agent from the liposomes at a temperature of between about +10 and 65 C.more » The invention further relates to the use of the liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.« less

Novel strategies for the formulation and processing of poorly water-soluble drugs.

PubMed

Göke, Katrin; Lorenz, Thomas; Repanas, Alexandros; Schneider, Frederic; Steiner, Denise; Baumann, Knut; Bunjes, Heike; Dietzel, Andreas; Finke, Jan H; Glasmacher, Birgit; Kwade, Arno

2018-05-01

Low aqueous solubility of active pharmaceutical ingredients presents a serious challenge in the development process of new drug products. This article provides an overview on some of the current approaches for the formulation of poorly water-soluble drugs with a special focus on strategies pursued at the Center of Pharmaceutical Engineering of the TU Braunschweig. These comprise formulation in lipid-based colloidal drug delivery systems and experimental as well as computational approaches towards the efficient identification of the most suitable carrier systems. For less lipophilic substances the preparation of drug nanoparticles by milling and precipitation is investigated for instance by means of microsystem-based manufacturing techniques and with special regard to the preparation of individualized dosage forms. Another option to overcome issues with poor drug solubility is the incorporation into nanospun fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-02-07

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

Electromagnetic field triggered drug and chemical delivery via liposomes

DOEpatents

Liburdy, R.P.

1993-03-02

The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release the chemical agent from the liposomes at a temperature of between about +10 and 65 C. The invention further relates to the use of the liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.

Electromagnetic field triggered drug and chemical delivery via liposomes

DOEpatents

Liburdy, Robert P.

1993-01-01

The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release said chemical agent from the liposomes at a temperature of between about +10 and 65.degree. C. The invention further relates to the use of said liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.

COmet Nucleus Dust and Organics Return (CONDOR): a New Frontiers 4 Mission Proposal

NASA Astrophysics Data System (ADS)

Choukroun, M.; Raymond, C.; Wadhwa, M.

2017-09-01

CONDOR would collect and return a ≥ 50 g sample from the surface of 67P/Churyumov-Gerasimenko for detailed analysis in terrestrial laboratories. It would carry a simple payload comprising a narrow-angle camera and mm-wave radiometer to select a sampling site, and perform a gravity science investigation to survey changes of 67P since Rosetta. The proposed sampling system uses the BiBlade tool to acquire a sample down to 15 cm depth in a Touch-and-Go event. The Stardust-based sample return capsule is augmented with cooling and purge systems to maintain sample integrity during landing and until delivery to JSC's Astromaterials Curation Facility. Analysis of rock-forming minerals, organics, water and noble gases would probe the origin of these materials, and their evolution from the primordial molecular cloud to the 67P environment.

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.

Promoting Collaboration in Health Care Teams through Interprofessional Education: A Simulation Case Study

ERIC Educational Resources Information Center

Ekmekci, Ozgur

2013-01-01

This simulation study explores how the integration of interprofessional components into health care curriculum may impact professional stereotyping and collaborative behavior in care delivery teams comprised of a physician, a registered nurse, a physician's assistant, a physical therapist, and a radiation therapist. As part of the agent-based…

Lights, Camera, Action: Facilitating the Design and Production of Effective Instructional Videos

ERIC Educational Resources Information Center

Di Paolo, Terry; Wakefield, Jenny S.; Mills, Leila A.; Baker, Laura

2017-01-01

This paper outlines a rudimentary process intended to guide faculty in K-12 and higher education through the steps involved to produce video for their classes. The process comprises four steps: planning, development, delivery and reflection. Each step is infused with instructional design information intended to support the collaboration between…

Current funding and financing issues in the Australian hospice and palliative care sector.

PubMed

Gordon, Robert; Eagar, Kathy; Currow, David; Green, Janette

2009-07-01

This article overviews current funding and financing issues in the Australian hospice and palliative care sector. Within Australia, the major responsibilities for managing the health care system are shared between two levels of government. Funding arrangements vary according to the type of care. The delivery of palliative care services is a State/Territory responsibility. Recently, almost all States/Territories have developed overarching frameworks to guide the development of palliative care policies, including funding and service delivery structures. Palliative care services in Australia comprise a mix of specialist providers, generalist providers, and support services in the public, nongovernment, and private sectors. The National Palliative Care Strategy is a joint strategy of the Commonwealth and States that commenced in 2002 and includes a number of major issues. Following a national study in 1996, the Australian National Subacute and Nonacute Patient (AN-SNAP) system was endorsed as the national casemix classification for subacute and nonacute care. Funding for palliative care services varies depending on the type of service and the setting in which it is provided. There is no national model for funding inpatient or community services, which is a State/Territory responsibility. A summary of funding arrangements is provided in this article. Palliative care continues to evolve at a rapid rate in Australia. Increasingly flexible evidence-based models of care delivery are emerging. This article argues that it will be critical for equally flexible funding and financing models to be developed. Furthermore, it is critical that palliative care patients can be identified, classified, and costed. Casemix classifications such as AN-SNAP represent an important starting point but further work is required.

Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs.

PubMed

Butt, Adeel Masood; Mohd Amin, Mohd Cairul Iqbal; Katas, Haliza

2015-01-01

Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells. FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue(®) assay. The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX-DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake.

Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

PubMed Central

Butt, Adeel Masood; Mohd Amin, Mohd Cairul Iqbal; Katas, Haliza

2015-01-01

Background Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells. Methods FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue® assay. Results The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX–DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. Conclusion FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake. PMID:25709451

A novel platform for minimally invasive delivery of cellular therapy as a thin layer across the subretina for treatment of retinal degeneration

NASA Astrophysics Data System (ADS)

Rotenstreich, Ygal; Tzameret, Adi; Kalish, Sapir E.; Belkin, Michael; Meir, Amilia; Treves, Avraham J.; Nagler, Arnon; Sher, Ifat

2015-03-01

Incurable retinal degenerations affect millions worldwide. Stem cell transplantation rescued visual functions in animal models of retinal degeneration. In those studies cells were transplanted in subretinal "blebs", limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection sites. We developed a minimally-invasive surgical platform for drug and cell delivery in a thin layer across the subretina and extravascular spaces of the choroid. The novel system is comprised of a syringe with a blunt-tipped needle and an adjustable separator. Human bone marrow mesenchymal stem cells (hBM-MSCs) were transplanted in eyes of RCS rats and NZW rabbits through a longitudinal triangular scleral incision. No immunosuppressants were used. Retinal function was determined by electroretinogram analysis and retinal structure was determined by histological analysis and OCT. Transplanted cells were identified as a thin layer across the subretina and extravascular spaces of the choroid. In RCS rats, cell transplantation delayed photoreceptor degeneration across the entire retina and significantly enhanced retinal functions. No retinal detachment or choroidal hemorrhages were observed in rabbits following transplantation. This novel platform opens a new avenue for drug and cell delivery, placing the transplanted cells in close proximity to the damaged RPE and retina as a thin layer, across the subretina and thereby slowing down cell death and photoreceptor degeneration, without retinal detachment or choroidal hemorrhage. This new transplantation system may increase the therapeutic effect of other cell-based therapies and therapeutic agents. This study is expected to directly lead to phase I/II clinical trials for autologous hBM-MSCs transplantation in retinal degeneration patients.

Millennial Filipino Student Engagement Analyzer Using Facial Feature Classification

NASA Astrophysics Data System (ADS)

Manseras, R.; Eugenio, F.; Palaoag, T.

2018-03-01

Millennials has been a word of mouth of everybody and a target market of various companies nowadays. In the Philippines, they comprise one third of the total population and most of them are still in school. Having a good education system is important for this generation to prepare them for better careers. And a good education system means having quality instruction as one of the input component indicators. In a classroom environment, teachers use facial features to measure the affect state of the class. Emerging technologies like Affective Computing is one of today’s trends to improve quality instruction delivery. This, together with computer vision, can be used in analyzing affect states of the students and improve quality instruction delivery. This paper proposed a system of classifying student engagement using facial features. Identifying affect state, specifically Millennial Filipino student engagement, is one of the main priorities of every educator and this directed the authors to develop a tool to assess engagement percentage. Multiple face detection framework using Face API was employed to detect as many student faces as possible to gauge current engagement percentage of the whole class. The binary classifier model using Support Vector Machine (SVM) was primarily set in the conceptual framework of this study. To achieve the most accuracy performance of this model, a comparison of SVM to two of the most widely used binary classifiers were tested. Results show that SVM bested RandomForest and Naive Bayesian algorithms in most of the experiments from the different test datasets.

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

PubMed

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

2017-01-01

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

X-ray system simulation software tools for radiology and radiography education.

PubMed

Kengyelics, Stephen M; Treadgold, Laura A; Davies, Andrew G

2018-02-01

To develop x-ray simulation software tools to support delivery of radiological science education for a range of learning environments and audiences including individual study, lectures, and tutorials. Two software tools were developed; one simulated x-ray production for a simple two dimensional radiographic system geometry comprising an x-ray source, beam filter, test object and detector. The other simulated the acquisition and display of two dimensional radiographic images of complex three dimensional objects using a ray casting algorithm through three dimensional mesh objects. Both tools were intended to be simple to use, produce results accurate enough to be useful for educational purposes, and have an acceptable simulation time on modest computer hardware. The radiographic factors and acquisition geometry could be altered in both tools via their graphical user interfaces. A comparison of radiographic contrast measurements of the simulators to a real system was performed. The contrast output of the simulators had excellent agreement with measured results. The software simulators were deployed to 120 computers on campus. The software tools developed are easy-to-use, clearly demonstrate important x-ray physics and imaging principles, are accessible within a standard University setting and could be used to enhance the teaching of x-ray physics to undergraduate students. Current approaches to teaching x-ray physics in radiological science lack immediacy when linking theory with practice. This method of delivery allows students to engage with the subject in an experiential learning environment. Copyright © 2017. Published by Elsevier Ltd.

Self-nanoemulsifying drug delivery system of nifedipine: impact of hydrophilic-lipophilic balance and molecular structure of mixed surfactants.

PubMed

Weerapol, Yotsanan; Limmatvapirat, Sontaya; Nunthanid, Jurairat; Sriamornsak, Pornsak

2014-04-01

A simple but novel mixed surfactant system was designed to fabricate a self-nanoemulsifying drug delivery system (SNEDDS) based on hydrophilic-lipophilic balance (HLB) value. The impacts of HLB and molecular structure of surfactants on the formation of SNEDDS were investigated. After screening various oils and surfactants, nifedipine (NDP)-loaded liquid SNEDDS was formulated with Imwitor(®) 742 as oil and Tween(®)/Span(®) or Cremophor(®)/Span(®) as mixed surfactant. Droplet size of the emulsions obtained after dispersing SNEDDS containing Tween(®)/Span(®) in aqueous medium was independent of the HLB of a mixed surfactant. The use of the Cremophor(®)/Span(®) blend gave nanosized emulsion at higher HLB. The structure of the surfactant was found to influence the emulsion droplet size. Solid SNEDDS was then prepared by adsorbing NDP-loaded liquid SNEDDS comprising Cremophor(®) RH40/Span(®) 80 onto Aerosil(®) 200 or Aerosil(®) R972 as inert solid carrier. Solid SNEDDS formulations using higher amounts (30-50% w/w) of Aerosil(®) 200 exhibited good flow properties with smooth surface and preserved the self-emulsifying properties of liquid SNEDDS. Differential scanning calorimetry and X-ray diffraction studies of solid SNEDDS revealed the transformation of the crystalline structure of NDP due to its molecular dispersion state. In vitro dissolution study demonstrated higher dissolution of NDP from solid SNEDDS compared with NDP powder.

Ultra High Mass Range Mass Spectrometer System

DOEpatents

Reilly, Peter T. A. [Knoxville, TN

2005-12-06

Applicant's present invention comprises mass spectrometer systems that operate in a mass range from 1 to 10.sup.16 DA. The mass spectrometer system comprising an inlet system comprising an aerodynamic lens system, a reverse jet being a gas flux generated in an annulus moving in a reverse direction and a multipole ion guide; a digital ion trap; and a thermal vaporization/ionization detector system. Applicant's present invention further comprises a quadrupole mass spectrometer system comprising an inlet system having a quadrupole mass filter and a thermal vaporization/ionization detector system. Applicant's present invention further comprises an inlet system for use with a mass spectrometer system, a method for slowing energetic particles using an inlet system. Applicant's present invention also comprises a detector device and a method for detecting high mass charged particles.

Transformable DNA Nanocarriers for Plasma Membrane Targeted Delivery of Cytokine

PubMed Central

Sun, Wujin; Ji, Wenyan; Hu, Quanyin; Yu, Jicheng; Wang, Chao; Qian, Chenggen; Hochu, Gabrielle; Gu, Zhen

2016-01-01

Direct delivery of cytokines using nanocarriers holds great promise for cancer therapy. However, the nanometric scale of the vehicles made them susceptible to size-dependent endocytosis, reducing the plasma membrane-associated apoptosis signalling. Herein, we report a tumor microenvironment-responsive and transformable nanocarrier for cell membrane targeted delivery of cytokine. This formulation is comprised of a phospholipase A2 (PLA2) degradable liposome as a shell, and complementary DNA nanostructures (designated as nanoclews) decorated with cytokines as the cores. Utilizing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a model cytokine, we demonstrate that the TRAIL loaded DNA nanoclews are capable of transforming into nanofibers after PLA2 activation. The nanofibers with micro-scaled lengths efficiently present the loaded TRAIL to death receptors on the cancer cell membrane and amplified the apoptotic signalling with reduced TRAIL internalization. PMID:27131597

Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging

PubMed Central

Mahdi, Elrashid Saleh; Noor, Azmin Mohd; Sakeena, Mohamed Hameem; Abdullah, Ghassan Z; Abdulkarim, Muthanna F; Sattar, Munavvar Abdul

2011-01-01

Background Recently there has been a remarkable surge of interest about natural products and their applications in the cosmetic industry. Topical delivery of antioxidants from natural sources is one of the approaches used to reverse signs of skin aging. The aim of this research was to develop a nanoemulsion cream for topical delivery of 30% ethanolic extract derived from local Phyllanthus urinaria (P. urinaria) for skin antiaging. Methods Palm kernel oil esters (PKOEs)-based nanoemulsions were loaded with P. urinaria extract using a spontaneous method and characterized with respect to particle size, zeta potential, and rheological properties. The release profile of the extract was evaluated using in vitro Franz diffusion cells from an artificial membrane and the antioxidant activity of the extract released was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method. Results Formulation F12 consisted of wt/wt, 0.05% P. urinaria extract, 1% cetyl alcohol, 0.5% glyceryl monostearate, 12% PKOEs, and 27% Tween® 80/Span® 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and a 59.5% phosphate buffer system at pH 7.4. Formulation F36 was comprised of 0.05% P. urinaria extract, 1% cetyl alcohol, 1% glyceryl monostearate, 14% PKOEs, 28% Tween® 80/Span® 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and 56% phosphate buffer system at pH 7.4 with shear thinning and thixotropy. The droplet size of F12 and F36 was 30.74 nm and 35.71 nm, respectively, and their nanosizes were confirmed by transmission electron microscopy images. Thereafter, 51.30% and 51.02% of the loaded extract was released from F12 and F36 through an artificial cellulose membrane, scavenging 29.89% and 30.05% of DPPH radical activity, respectively. Conclusion The P. urinaria extract was successfully incorporated into a PKOEs-based nanoemulsion delivery system. In vitro release of the extract from the formulations showed DPPH radical scavenging activity. These formulations can neutralize reactive oxygen species and counteract oxidative injury induced by ultraviolet radiation and thereby ameliorate skin aging. PMID:22072884

Design of a composite drug delivery system to prolong functionality of cell-based scaffolds.

PubMed

Murua, Ainhoa; Herran, Enara; Orive, Gorka; Igartua, Manoli; Blanco, Francisco Javier; Pedraz, José Luis; Hernández, Rosa M

2011-04-04

Cell encapsulation technology raises hopes in medicine and biotechnology. However, despite important advances in the field in the past three decades, several challenges associated with the biocompatibility are still remaining. In the present study, the effect of a temporary release of an anti-inflammatory agent on co-administered encapsulated allogeneic cells was investigated. The aim was to determine the biocompatibility and efficacy of the approach to prevent the inflammatory response. A composite delivery system comprised of alginate-poly-l-lysine-alginate (APA)-microencapsulated Epo-secreting myoblasts and dexamethasone (DXM)-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres was implanted in the subcutaneous space of Balb/c mice for 45 days. The use of independently co-implanted DXM-loaded PLGA microspheres resulted in an improved functionality of the cell-based graft, evidenced by significantly higher hematocrit levels found in the cell-implanted groups by day 45, which was found to be more pronounced when higher cell-doses (100 μL) were employed. Moreover, no major host reaction was observed upon implantation of the systems, showing good biocompatibility and capability to partially avoid the inflammatory response, probably due to the immunosuppressive effects related to DXM. The findings of this study imply that DXM-loaded PLGA microspheres show promise as release systems to enhance biocompatibility and offer advantage in the development of long-lasting and effective implantable microencapsulated cells by generating a potential immunopriviledged local environment and an effective method to limit the structural ensheathing layer caused by inflammation. Copyright © 2010 Elsevier B.V. All rights reserved.

Advanced Materials and Processing for Drug Delivery: The Past and the Future

PubMed Central

Zhang, Ying; Chan, Hon Fai; Leong, Kam W.

2012-01-01

Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. PMID:23088863

Lysimeter methods and apparatus

DOEpatents

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

2004-12-07

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

The impact of direct provision accommodation for asylum seekers on organisation and delivery of local primary care and social care services: A case study

PubMed Central

2011-01-01

Background Many western countries have policies of dispersal and direct provision accommodation (state-funded accommodation in an institutional centre) for asylum seekers. Most research focuses on its effect on the asylum seeking population. Little is known about the impact of direct provision accommodation on organisation and delivery of local primary care and social care services in the community. The aim of this research is to explore this issue. Methods In 2005 a direct provision accommodation centre was opened in a rural area in Ireland. A retrospective qualitative case study was designed comprising in-depth interviews with 37 relevant stakeholders. Thematic analysis following the principles of framework analysis was applied. Results There was lack of advance notification to primary care and social care professionals and the community about the new accommodation centre. This caused anxiety and stress among relevant stakeholders. There was insufficient time to plan and prepare appropriate primary care and social care for the residents, causing a significant strain on service delivery. There was lack of clarity about how primary care and social care needs of the incoming residents were to be addressed. Interdisciplinary support systems developed informally between healthcare professionals. This ensured that residents of the accommodation centre were appropriately cared for. Conclusions Direct provision accommodation impacts on the organisation and delivery of local primary care and social care services. There needs to be sufficient advance notification and inter-agency, inter-professional dialogue to manage this. Primary care and social care professionals working with asylum seekers should have access to training to enhance their skills for working in cross-cultural consultations. PMID:21575159

The impact of direct provision accommodation for asylum seekers on organisation and delivery of local primary care and social care services: a case study.

PubMed

Pieper, Hans-Olaf; Clerkin, Pauline; MacFarlane, Anne

2011-05-15

Many western countries have policies of dispersal and direct provision accommodation (state-funded accommodation in an institutional centre) for asylum seekers. Most research focuses on its effect on the asylum seeking population. Little is known about the impact of direct provision accommodation on organisation and delivery of local primary care and social care services in the community. The aim of this research is to explore this issue. In 2005 a direct provision accommodation centre was opened in a rural area in Ireland. A retrospective qualitative case study was designed comprising in-depth interviews with 37 relevant stakeholders. Thematic analysis following the principles of framework analysis was applied. There was lack of advance notification to primary care and social care professionals and the community about the new accommodation centre. This caused anxiety and stress among relevant stakeholders. There was insufficient time to plan and prepare appropriate primary care and social care for the residents, causing a significant strain on service delivery. There was lack of clarity about how primary care and social care needs of the incoming residents were to be addressed. Interdisciplinary support systems developed informally between healthcare professionals. This ensured that residents of the accommodation centre were appropriately cared for. Direct provision accommodation impacts on the organisation and delivery of local primary care and social care services. There needs to be sufficient advance notification and inter-agency, inter-professional dialogue to manage this. Primary care and social care professionals working with asylum seekers should have access to training to enhance their skills for working in cross-cultural consultations.

Translating knowledge into best practice care bundles: a pragmatic strategy for EBP implementation via moving postprocedural pain management nursing guidelines into clinical practice.

PubMed

Saunders, Hannele

2015-07-01

To describe quantitative and qualitative best evidence as sources for practical interventions usable in daily care delivery in order to integrate best evidence into clinical decision-making at local practice settings. To illustrate the development, implementation and evaluation of a pain management nursing care bundle based on a clinical practice guideline via a real-world clinical exemplar. Successful implementation of evidence-based practice requires consistent integration of best evidence into daily clinical decision-making. Best evidence comprises high-quality knowledge summarised in systematic reviews and translated into guidelines. However, consistent integration of guidelines into care delivery remains challenging, partly due to guidelines not being in a usable form for daily practice or relevant for the local context. A position paper with a clinical exemplar of a nurse-led, evidence-based quality improvement project to design, implement and evaluate a pain management care bundle translated from a national nursing guideline. A pragmatic approach to integrating guidelines into daily practice is presented. Best evidence from a national nursing guideline was translated into a pain management care bundle and integrated into daily practice in 15 medical-surgical (med-surg) units of nine hospitals of a large university hospital system in Finland. Translation of best evidence from guidelines into usable form as care bundles adapted to the local setting may increase implementation and uptake of guidelines and improve quality and consistency of care delivery. A pragmatic approach to translating a nursing guideline into a pain management care bundle to incorporate best evidence into daily practice may help achieve more consistent and equitable integration of guidelines into care delivery, and better quality of pain management and patient outcomes. © 2015 John Wiley & Sons Ltd.

Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap(®) System.

PubMed

Koziolek, Mirko; Grimm, Michael; Becker, Dieter; Iordanov, Ventzeslav; Zou, Hans; Shimizu, Jeff; Wanke, Christoph; Garbacz, Grzegorz; Weitschies, Werner

2015-09-01

Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated in two studies with each 10 healthy human subjects using the IntelliCap(®) system. This telemetric drug delivery device enabled the determination of gastric emptying time, small bowel transit time, and colon arrival time by significant pH and temperature changes. The study results revealed high variability of GI pH and transit times. The gastric transit of IntelliCap(®) was characterized by high fluctuations of the pH with mean values ranging from pH 1.7 to pH 4.7. Gastric emptying was observed after 7-202 min (median: 30 min). During small bowel transit, which had a duration of 67-532 min (median: 247 min), pH values increased slightly from pH 5.9-6.3 in proximal parts to pH 7.4-7.8 in distal parts. Colonic pH conditions were characterized by values fluctuating mainly between pH 5 and pH 8. The pH profiles and transit times described in this work are highly relevant for the comprehension of drug delivery of solid oral dosage forms comprising ionizable drugs and excipients with pH-dependent solubility. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Healthcare in the New Vietnam: comparing patients' satisfaction with outpatient care in a traditional neighborhood clinic and a new, western-style clinic in Ho Chi Minh City.

PubMed

Tat, Sonny; Barr, Donald

2006-03-01

As Vietnam opens its economy to privatization, its system of healthcare will face a series of crucial tests. Vietnam's system of private healthcare--once comprised only of individual physicians holding clinic hours in their homes--has come to also include larger customer-oriented clinics based on an American business model. As the two models compete in the expanding private market, it becomes increasingly important to understand patients' perceptions of the alternative models of care. This study reports on interviews with 194 patients in two different types of private-sector clinics in Vietnam: a western-style clinic and a traditional style, after-hours clinic. In bivariate and multivariate analyses, we found that patients at the western style clinic reported both higher expectations of the facility and higher satisfaction with many aspects of care than patients at the after-hours clinic. These different perceptions appear to be based on the interpersonal manner of the physician seen and the clinic's delivery methods rather than perceptions of the physician's technical skill and method of treatment. These findings were unaffected by the ethnicity of physician seen. These findings suggest that patients in Vietnam recognize and prefer more customer-oriented care and amenities, regardless of physician ethnicity and perceive no significant differences in technical skill between the private delivery models.

Theranostic nanoparticles for the treatment of cancer

NASA Astrophysics Data System (ADS)

Moore, Thomas Lee

The main focus of this research was to evaluate the ability of a novel multifunctional nanoparticle to mediate drug delivery and enable a non-invasive approach to measure drug release kinetics in situ for the treatment of cancer. These goals were approached by developing a nanoparticle consisting of an inorganic core (i.e. gadolinium sulfoxide doped with europium ions or carbon nanotubes). This was coated with an external amphiphilic polymer shell comprised of a biodegradable polyester (i.e. poly(lactide) or poly(glycolide)), and poly(ethylene glycol) block copolymer. In this system, the inorganic core mediates the imaging aspect, the relatively hydrophobic polyester encapsulates hydrophobic anti-cancer drugs, and poly(ethylene glycol) stabilizes the nanoparticle in an aqueous environment. The synthesis of this nanoparticle drug delivery system utilized a simple one-pot room temperature ring-opening polymerization that neglected the use of potentially toxic catalysts and reduced the number of washing steps. This functionalization approach could be applied across a number of inorganic nanoparticle platforms. Coating inorganic nanoparticles with biodegradable polymer was shown to decrease in vitro and in vivo toxicity. Nanoparticles could be further coated with multiple polymer layers to better control drug release characteristics. Finally, loading polymer coated radioluminescent nanoparticles with photoactive drugs enabled a mechanism for measuring drug concentration in situ. The work presented here represents a step forward to developing theranostic nanoparticles that can improve the treatment of cancer.

The value of local registry data for describing cervical cancer management and outcomes over three decades in Australia.

PubMed

Roder, D; Davy, M; Selva-Nayagam, S; Gowda, R; Paramasivam, S; Adams, J; Keefe, D; Eckert, M; Powell, K; Fusco, K; Buranyi-Trevarton, D; Oehler, M K

2018-01-01

Registry data on invasive cervical cancers (n = 1,274) from four major hospitals (1984-2012) were analysed to determine their value for informing local service delivery in Australia. The methodology comprised disease-specific survival analyses using Kaplan-Meier product-limit estimates and Cox proportional hazards models and treatment analyses using logistic regression. Five- and 10-year survivals were 72% and 68%, respectively, equating with relative survival estimates for Australia and the USA. Most common treatments were surgery and radiotherapy. Systemic therapies increased in recent years, generally with radiotherapy, but were less common for residents from less accessible areas. Surgery was more common for younger women and early-stage disease, and radiotherapy for older women and regional and more advanced disease. The proportion of glandular cancers increased in-step with national trends. Little evidence of variation in risk-adjusted survival presented over time or by Local Health District. The study illustrates the value of local registry data for describing local treatment and outcomes. They show the lower use of systemic therapies among residents of less accessible areas which warrants further investigation. Risk-adjusted treatment and outcomes did not vary by socio-economic status, suggesting equity in service delivery. These data are important for local evaluation and were not available from other sources. © 2017 John Wiley & Sons Ltd.

Comparison of vaccine efficacy for different antigen delivery systems for infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L.) in a cohabitation challenge model.

PubMed

Munang'andu, Hetron M; Fredriksen, Børge N; Mutoloki, Stephen; Brudeseth, Bjørn; Kuo, Tsun-Yung; Marjara, Inderjit S; Dalmo, Roy A; Evensen, Øystein

2012-06-08

Two strains of IPNV made by reverse genetics on the Norwegian Sp strain NVI-015 (GenBank AY379740) backbone encoding the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs were used to prepare inactivated whole virus (IWV), nanoparticle vaccines with whole virus, Escherichia coli subunit encoding truncated VP2-TA and VP2-PT, VP2-TA and VP2-PT fusion antigens with putative translocating domains of Pseudomonas aeruginosa exotoxin, and plasmid DNA encoding segment A of the TA strain. Post challenge survival percentages (PCSP) showed that IWV vaccines conferred highest protection (PCSP=42-53) while nanoparticle, sub-unit recombinant and DNA vaccines fell short of the IWV vaccines in Atlantic salmon (Salmo salar L.) postsmolts challenged with the highly virulent Sp strain NVI-015 (TA strain) of IPNV after 560 degree days post vaccination. Antibody levels induced by these vaccines did not show antigenic differences between the virulent and avirulent motifs for vaccines made with the same antigen dose and delivery system after 8 weeks post vaccination. Our findings show that fish vaccinated with less potent vaccines comprising of nanoparticle, DNA and recombinant vaccines got infected much earlier and yielded to higher infection rates than fish vaccinated with IWV vaccines that were highly potent. Ability of the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs to limit establishment of infection showed equal protection for vaccines made of the same antigen dose and delivery systems. Prevention of tissue damage linked to viral infection was eminent in the more potent vaccines than the less protective ones. Hence, there still remains the challenge of developing highly efficacious vaccines with the ability to eliminate the post challenge carrier state in IPNV vaccinology. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fuel system for rotary distributor fuel injection pump

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

Klopfer, K.H.; Kelly, W.W.

1993-06-01

In a fuel injection pump having a drive shaft, a pump rotor driven by the drive shaft, reciprocating pumping means with periodic intake and pumping strokes to periodically receive an intake charge of fuel and deliver fuel at high pressure for fuel injection is described; a distributor head with a plurality of angularly spaced distributor outlets, the pump rotor providing a distributor rotor with a distributor port connected to the pumping means, the distributor rotor being rotatably mounted in the distributor head for sequential registration of the distributor port with the distributor outlets for distributing said high pressure delivery ofmore » fuel thereto; a fuel system for supplying fuel to the pumping means, having an end chamber at one end of the pump rotor and a fuel supply pump driven by the drive shaft and having an inlet and outlet, the supply pump outlet being connected to the end chamber for supplying fuel thereto, and a pressure regulator for regulating the fuel pressure in the end chamber; and a control valve connected between the pumping means and the end chamber and selectively opened during the intake strokes to supply fuel to the pumping means from the end chamber and during the pumping strokes to spill fuel from the pumping means into the end chamber to terminate said high pressure delivery of fuel; the improvement wherein the fuel system comprises a fuel return passage connected in series with the end chamber downstream thereof, wherein the pressure regulator is mounted in the return passage for regulating the upstream fuel pressure, including the upstream fuel pressure within the end chamber, and is connected for conducting excess fuel for return to the supply pump inlet, and wherein the supply pump is driven by the drive shaft to supply fuel at a rate exceeding the rate of said high pressure delivery of fuel for fuel injection and to provide excess fuel flow continuously through the end chamber and return passage to the pressure regulator.« less

Multi-Layer Self-Nanoemulsifying Pellets: an Innovative Drug Delivery System for the Poorly Water-Soluble Drug Cinnarizine.

PubMed

Shahba, Ahmad Abdul-Wahhab; Ahmed, Abid Riaz; Alanazi, Fars Kaed; Mohsin, Kazi; Abdel-Rahman, Sayed Ibrahim

2018-04-25

Beside their solubility limitations, some poorly water-soluble drugs undergo extensive degradation in aqueous and/or lipid-based formulations. Multi-layer self-nanoemulsifying pellets (ML-SNEP) introduce an innovative delivery system based on isolating the drug from the self-nanoemulsifying layer to enhance drug aqueous solubility and minimize degradation. In the current study, various batches of cinnarizine (CN) ML-SNEP were prepared using fluid bed coating and involved a drug-free self-nanoemulsifying layer, protective layer, drug layer, moisture-sealing layer, and/or an anti-adherent layer. Each layer was optimized based on coating outcomes such as coating recovery and mono-pellets%. The optimized ML-SNEP were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro dissolution, and stability studies. The optimized ML-SNEP were free-flowing, well separated with high coating recovery. SEM showed multiple well-defined coating layers. The acidic polyvinylpyrrolidone:CN (4:1) solution presented excellent drug-layering outcomes. DSC and XRD confirmed CN transformation into amorphous state within the drug layer. The isolation between CN and self-nanoemulsifying layer did not adversely affect drug dissolution. CN was able to spontaneously migrate into the micelles arising from the drug-free self-nanoemulsifying layer. ML-SNEP showed superior dissolution compared to Stugeron® tablets at pH 1.2 and 6.8. Particularly, on shifting to pH 6.8, ML-SNEP maintained > 84% CN in solution while Stugeron® tablets showed significant CN precipitation leaving only 7% CN in solution. Furthermore, ML-SNEP (comprising Kollicoat® Smartseal 30D) showed robust stability and maintained > 97% intact CN within the accelerated storage conditions. Accordingly, ML-SNEP offer a novel delivery system that combines both enhanced solubilization and stabilization of unstable poorly soluble drugs.

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…

Making capitated Medicare work for women: policy and research challenges.

PubMed

Bierman, A S; Clancy, C M

2000-01-01

Growth in capitated Medicare has special ramifications for older women who comprise the majority of Medicare beneficiaries. Older women are more likely than men to have chronic conditions that lead to illness and disability, and they often have fewer financial and social resources to cope with these problems. Gender differences in health status have a number of important implications for the financing and delivery of care for older women under both traditional fee-for-service Medicare and capitation. The utilization of effective preventive interventions, new therapeutic interventions for the management of common chronic disorders, and more cost-effective models of chronic disease management could potentially extend the active life expectancy of older women. However, there are financial and delivery system barriers to achieving these objectives. Traditional FFS Medicare has gaps in coverage of care for chronic illness and disability that disproportionately impact women. Managed care potentially offers flexibility to allocate resources creatively, to develop new models of care, and offer enhanced benefits with lower out-of-pocket costs. However, challenges to realizing this potential under Medicare managed care with unique implications for older women include: possible gender bias in capitation payments, risk selection, inadequacy of risk adjustment models, benefit and market instability, and disenrollment patterns.

Efficient distribution of toy products using ant colony optimization algorithm

NASA Astrophysics Data System (ADS)

Hidayat, S.; Nurpraja, C. A.

2017-12-01

CV Atham Toys (CVAT) produces wooden toys and furniture, comprises 13 small and medium industries. CVAT always attempt to deliver customer orders on time but delivery costs are high. This is because of inadequate infrastructure such that delivery routes are long, car maintenance costs are high, while fuel subsidy by the government is still temporary. This study seeks to minimize the cost of product distribution based on the shortest route using one of five Ant Colony Optimization (ACO) algorithms to solve the Vehicle Routing Problem (VRP). This study concludes that the best of the five is the Ant Colony System (ACS) algorithm. The best route in 1st week gave a total distance of 124.11 km at a cost of Rp 66,703.75. The 2nd week route gave a total distance of 132.27 km at a cost of Rp 71,095.13. The 3rd week best route gave a total distance of 122.70 km with a cost of Rp 65,951.25. While the 4th week gave a total distance of 132.27 km at a cost of Rp 74,083.63. Prior to this study there was no effort to calculate these figures.

STS-97 P6 truss payload canister is lifted into payload changeout room

NASA Technical Reports Server (NTRS)

2000-01-01

On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, is lifted toward the payload changeout room (PCR). The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure that supports payload delivery at the pad and subsequent vertical installation in the orbiter payload bay. Attached to the canister are the red umbilical lines that maintain the controlled environment inside. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station'''s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a '''blanket''' that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST.

KSC-00pp1736

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- The payload transport canister, with the P6 integrated truss segment inside, is close to the payload changeout room on the Rotating Service Structure (RSS) at left. The PCR is the enclosed, environmentally controlled portion of the RSS that supports payload delivery at the pad. At right is Space Shuttle Endeavour with its orange external tank and one solid rocket booster showing behind it. When the RSS is closed around Endeavour, the P6 truss will be moved into the orbiter’s payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC00pp1730

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister waits at the base of the Rotating Service Structure (RSS) with the P6 integrated truss segment inside. The canister will be lifted up to the payload changeout room (PCR) where the P6 will be removed for transfer to Space Shuttle Endeavour’s payload bay. The PCR is the enclosed, environmentally controlled portion of the RSS that supports payload delivery at the pad and subsequent vertical installation in the orbiter payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC00pp1736

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- The payload transport canister, with the P6 integrated truss segment inside, is close to the payload changeout room on the Rotating Service Structure (RSS) at left. The PCR is the enclosed, environmentally controlled portion of the RSS that supports payload delivery at the pad. At right is Space Shuttle Endeavour with its orange external tank and one solid rocket booster showing behind it. When the RSS is closed around Endeavour, the P6 truss will be moved into the orbiter’s payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC-00pp1730

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister waits at the base of the Rotating Service Structure (RSS) with the P6 integrated truss segment inside. The canister will be lifted up to the payload changeout room (PCR) where the P6 will be removed for transfer to Space Shuttle Endeavour’s payload bay. The PCR is the enclosed, environmentally controlled portion of the RSS that supports payload delivery at the pad and subsequent vertical installation in the orbiter payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

Aloe vera: Nature's soothing healer to periodontal disease

PubMed Central

Bhat, Geetha; Kudva, Praveen; Dodwad, Vidya

2011-01-01

Background: Recent interest and advances in the field of alternative medicine has promoted the use of various herbal and natural products for multiple uses in the field of medicine. Aloe vera is one such product exhibiting multiple benefits and has gained considerable importance in clinical research. This clinical study focuses on Aloe vera and highlights its property when used as a medicament in the periodontal pocket. Materials and Methods: A total number of 15 subjects were evaluated for clinical parameters like plaque index, gingival index, probing pocket depth at baseline, followed by scaling and root planing (SRP). Test site comprised of SRP followed by intra-pocket placement of Aloe vera gel, which was compared with the control site in which only SRP was done, and clinical parameters were compared between the two sites at one month and three months from baseline. Results: Results exhibited encouraging findings in clinical parameters of the role of Aloe vera gel as a drug for local delivery. Conclusion: We conclude that subgingival administration of Aloe vera gel results in improvement of periodontal condition. Aloe vera gel can be used as a local drug delivery system in periodontal pockets. PMID:22028505

An Extended EPQ-Based Problem with a Discontinuous Delivery Policy, Scrap Rate, and Random Breakdown

PubMed Central

Song, Ming-Syuan; Chen, Hsin-Mei; Chiu, Yuan-Shyi P.

2015-01-01

In real supply chain environments, the discontinuous multidelivery policy is often used when finished products need to be transported to retailers or customers outside the production units. To address this real-life production-shipment situation, this study extends recent work using an economic production quantity- (EPQ-) based inventory model with a continuous inventory issuing policy, defective items, and machine breakdown by incorporating a multiple delivery policy into the model to replace the continuous policy and investigates the effect on the optimal run time decision for this specific EPQ model. Next, we further expand the scope of the problem to combine the retailer's stock holding cost into our study. This enhanced EPQ-based model can be used to reflect the situation found in contemporary manufacturing firms in which finished products are delivered to the producer's own retail stores and stocked there for sale. A second model is developed and studied. With the help of mathematical modeling and optimization techniques, the optimal run times that minimize the expected total system costs comprising costs incurred in production units, transportation, and retail stores are derived, for both models. Numerical examples are provided to demonstrate the applicability of our research results. PMID:25821853

An extended EPQ-based problem with a discontinuous delivery policy, scrap rate, and random breakdown.

PubMed

Chiu, Singa Wang; Lin, Hong-Dar; Song, Ming-Syuan; Chen, Hsin-Mei; Chiu, Yuan-Shyi P

2015-01-01

In real supply chain environments, the discontinuous multidelivery policy is often used when finished products need to be transported to retailers or customers outside the production units. To address this real-life production-shipment situation, this study extends recent work using an economic production quantity- (EPQ-) based inventory model with a continuous inventory issuing policy, defective items, and machine breakdown by incorporating a multiple delivery policy into the model to replace the continuous policy and investigates the effect on the optimal run time decision for this specific EPQ model. Next, we further expand the scope of the problem to combine the retailer's stock holding cost into our study. This enhanced EPQ-based model can be used to reflect the situation found in contemporary manufacturing firms in which finished products are delivered to the producer's own retail stores and stocked there for sale. A second model is developed and studied. With the help of mathematical modeling and optimization techniques, the optimal run times that minimize the expected total system costs comprising costs incurred in production units, transportation, and retail stores are derived, for both models. Numerical examples are provided to demonstrate the applicability of our research results.

The stoma appliances market in five European countries: a comparative analysis.

PubMed

Cornago, Dante; Garattini, Livio

2002-01-01

This comparative exercise analysed the domestic market for stoma appliances in five European countries--Denmark, France, Germany, Italy and the United Kingdom. National legislation, prescription procedures, delivery modalities and the market were investigated in each country. The analysis involved reviewing national and international literature on stoma appliances and interviewing a selected expert panel of market operators in each country comprising at least one health authority representative, one distributor of medical devices and one manufacturer. No specific relationship was found between the health care system framework and the stoma market, except for a greater inclination towards home care in national health services. All five countries reimburse stoma bags, but the distribution of these appliances varies widely, ranging from Denmark, where home delivery is mandatory, to Italy, where any channel can be used. The comparative analysis underlined two important features of the stoma bag market: the discretion of enterostomists in directing patients towards a specific brand of bags, and the patients' high brand loyalty. Despite that, the analysis did not identify any single country that could be considered a benchmark for stoma bag regulation. Each country deals with stoma appliances in different ways, making this a very fragmented market.

Promoting tissue regeneration by modulating the immune system.

PubMed

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support existing regenerative strategies or could be an alternative to using stem cells and growth factors. The first part of this review we highlight key immune mechanisms involved in the tissue healing process and marks them as potential target for designing regenerative strategies. In the second part, we discuss various approaches using biomaterials and drug delivery systems that aim at modulating the components of the immune system to promote tissue regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Implementation and results of an integrated data quality assurance protocol in a randomized controlled trial in Uttar Pradesh, India.

PubMed

Gass, Jonathon D; Misra, Anamika; Yadav, Mahendra Nath Singh; Sana, Fatima; Singh, Chetna; Mankar, Anup; Neal, Brandon J; Fisher-Bowman, Jennifer; Maisonneuve, Jenny; Delaney, Megan Marx; Kumar, Krishan; Singh, Vinay Pratap; Sharma, Narender; Gawande, Atul; Semrau, Katherine; Hirschhorn, Lisa R

2017-09-07

There are few published standards or methodological guidelines for integrating Data Quality Assurance (DQA) protocols into large-scale health systems research trials, especially in resource-limited settings. The BetterBirth Trial is a matched-pair, cluster-randomized controlled trial (RCT) of the BetterBirth Program, which seeks to improve quality of facility-based deliveries and reduce 7-day maternal and neonatal mortality and maternal morbidity in Uttar Pradesh, India. In the trial, over 6300 deliveries were observed and over 153,000 mother-baby pairs across 120 study sites were followed to assess health outcomes. We designed and implemented a robust and integrated DQA system to sustain high-quality data throughout the trial. We designed the Data Quality Monitoring and Improvement System (DQMIS) to reinforce six dimensions of data quality: accuracy, reliability, timeliness, completeness, precision, and integrity. The DQMIS was comprised of five functional components: 1) a monitoring and evaluation team to support the system; 2) a DQA protocol, including data collection audits and targets, rapid data feedback, and supportive supervision; 3) training; 4) standard operating procedures for data collection; and 5) an electronic data collection and reporting system. Routine audits by supervisors included double data entry, simultaneous delivery observations, and review of recorded calls to patients. Data feedback reports identified errors automatically, facilitating supportive supervision through a continuous quality improvement model. The five functional components of the DQMIS successfully reinforced data reliability, timeliness, completeness, precision, and integrity. The DQMIS also resulted in 98.33% accuracy across all data collection activities in the trial. All data collection activities demonstrated improvement in accuracy throughout implementation. Data collectors demonstrated a statistically significant (p = 0.0004) increase in accuracy throughout consecutive audits. The DQMIS was successful, despite an increase from 20 to 130 data collectors. In the absence of widely disseminated data quality methods and standards for large RCT interventions in limited-resource settings, we developed an integrated DQA system, combining auditing, rapid data feedback, and supportive supervision, which ensured high-quality data and could serve as a model for future health systems research trials. Future efforts should focus on standardization of DQA processes for health systems research. ClinicalTrials.gov identifier, NCT02148952 . Registered on 13 February 2014.

Sugar-based amphiphilic polymers for biomedical applications: from nanocarriers to therapeutics.

PubMed

Gu, Li; Faig, Allison; Abdelhamid, Dalia; Uhrich, Kathryn

2014-10-21

Various therapeutics exhibit unfavorable physicochemical properties or stability issues that reduce their in vivo efficacy. Therefore, carriers able to overcome such challenges and deliver therapeutics to specific in vivo target sites are critically needed. For instance, anticancer drugs are hydrophobic and require carriers to solubilize them in aqueous environments, and gene-based therapies (e.g., siRNA or pDNA) require carriers to protect the anionic genes from enzymatic degradation during systemic circulation. Polymeric micelles, which are self-assemblies of amphiphilic polymers (APs), constitute one delivery vehicle class that has been investigated for many biomedical applications. Having a hydrophobic core and a hydrophilic shell, polymeric micelles have been used as drug carriers. While traditional APs are typically comprised of nondegradable block copolymers, sugar-based amphiphilic polymers (SBAPs) synthesized by us are comprised of branched, sugar-based hydrophobic segments and a hydrophilic poly(ethylene glycol) chain. Similar to many amphiphilic polymers, SBAPs self-assemble into polymeric micelles. These nanoscale micelles have extremely low critical micelle concentrations offering stability against dilution, which occurs with systemic administration. In this Account, we illustrate applications of SBAPs for anticancer drug delivery via physical encapsulation within SBAP micelles and chemical conjugation to form SBAP prodrugs capable of micellization. Additionally, we show that SBAPs are excellent at stabilizing liposomal delivery systems. These SBAP-lipid complexes were developed to deliver hydrophobic anticancer therapeutics, achieving preferential uptake in cancer cells over normal cells. Furthermore, these complexes can be designed to electrostatically complex with gene therapies capable of transfection. Aside from serving as a nanocarrier, SBAPs have also demonstrated unique bioactivity in managing atherosclerosis, a major cause of cardiovascular disease. The atherosclerotic cascade is usually triggered by the unregulated uptake of oxidized low-density lipoprotein, a cholesterol carrier, in macrophages of the blood vessel wall; SBAPs can significantly inhibit oxidized low-density lipoprotein uptake in macrophages and abrogate the atherosclerotic cascade. By modification of various functionalities (e.g., branching, stereochemistry, hydrophobicity, and charge) in the SBAP chemical structure, SBAP bioactivity was optimized, and influential structural components were identified. Despite the potential of SBAPs as atherosclerotic therapies, blood stability of the SBAP micelles was not ideal for in vivo applications, and means to stabilize them were pursued. Using kinetic entrapment via flash nanoprecipitation, SBAPs were formulated into nanoparticles with a hydrophobic solute core and SBAP shell. SBAP nanoparticles exhibited excellent physiological stability and enhanced bioactivity compared with SBAP micelles. Further, this method enables encapsulation of additional hydrophobic drugs (e.g., vitamin E) to yield a stable formulation that releases two bioactives. Both as nanoscale carriers and as polymer therapeutics, SBAPs are promising biomaterials for medical applications.

Two denominators for one numerator: the example of neonatal mortality.

PubMed

Harmon, Quaker E; Basso, Olga; Weinberg, Clarice R; Wilcox, Allen J

2018-06-01

Preterm delivery is one of the strongest predictors of neonatal mortality. A given exposure may increase neonatal mortality directly, or indirectly by increasing the risk of preterm birth. Efforts to assess these direct and indirect effects are complicated by the fact that neonatal mortality arises from two distinct denominators (i.e. two risk sets). One risk set comprises fetuses, susceptible to intrauterine pathologies (such as malformations or infection), which can result in neonatal death. The other risk set comprises live births, who (unlike fetuses) are susceptible to problems of immaturity and complications of delivery. In practice, fetal and neonatal sources of neonatal mortality cannot be separated-not only because of incomplete information, but because risks from both sources can act on the same newborn. We use simulations to assess the repercussions of this structural problem. We first construct a scenario in which fetal and neonatal factors contribute separately to neonatal mortality. We introduce an exposure that increases risk of preterm birth (and thus neonatal mortality) without affecting the two baseline sets of neonatal mortality risk. We then calculate the apparent gestational-age-specific mortality for exposed and unexposed newborns, using as the denominator either fetuses or live births at a given gestational age. If conditioning on gestational age successfully blocked the mediating effect of preterm delivery, then exposure would have no effect on gestational-age-specific risk. Instead, we find apparent exposure effects with either denominator. Except for prediction, neither denominator provides a meaningful way to define gestational-age-specific neonatal mortality.

The Formation of Communities of Practice in a Network of Schools Serving Culturally and Linguistically Diverse Students

ERIC Educational Resources Information Center

Scanlan, Martin; Zisselsberger, Margarita

2015-01-01

Culturally and linguistically diverse (CLD) students comprise the most rapidly expanding, and among the most educationally marginalized, group in the United States. CLD students' opportunities to learn are often diminished through service delivery models that are deficit-oriented, viewing linguistic diversity as a challenge to overcome, not a…

Cellulose binding domain proteins

DOEpatents

Shoseyov, O.; Shpiegl, I.; Goldstein, M.; Doi, R.

1998-11-17

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

Cellulose binding domain proteins

DOEpatents

Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

1998-01-01

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

Cellulose binding domain fusion proteins

DOEpatents

Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

1998-01-01

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

Adapting to Sydney's local government boundaries changes: a population health perspective.

PubMed

Assareh, Hassan; Achat, Helen M; Bag, Shopna; Moerkerken, Leendert; Gabriel, Salwa

2018-06-14

The territory of a Local Health District (LHD) comprises multiple local government areas (LGAs). The recent amalgamation of several LGAs in metropolitan Sydney has resulted in two new LGAs being expanded across multiple LHDs, resulting in nonconcordance of boundaries. Here, we discuss the implications for planning health activities and service delivery, and ways to address them.

Comparative health systems research among Kaiser Permanente and other integrated delivery systems: a systematic literature review.

PubMed

Maeda, Jared Lane K; Lee, Karen M; Horberg, Michael

2014-01-01

Because of rising health care costs, wide variations in quality, and increased patient complexity, the US health care system is undergoing rapid changes that include payment reform and movement toward integrated delivery systems. Well-established integrated delivery systems, such as Kaiser Permanente (KP), should work to identify the specific system-level factors that result in superior patient outcomes in response to policymakers' concerns. Comparative health systems research can provide insights into which particular aspects of the integrated delivery system result in improved care delivery. To provide a baseline understanding of comparative health systems research related to integrated delivery systems and KP. Systematic literature review. We conducted a literature search on PubMed and the KP Publications Library. Studies that compared KP as a system or organization with other health care systems or across KP facilities internally were included. The literature search identified 1605 articles, of which 65 met the study inclusion criteria and were examined by 3 reviewers. Most comparative health systems studies focused on intra-KP comparisons (n = 42). Fewer studies compared KP with other US (n = 15) or international (n = 12) health care systems. Several themes emerged from the literature as possible factors that may contribute to improved care delivery in integrated delivery systems. Of all studies published by or about KP, only a small proportion of articles (4%) was identified as being comparative health systems research. Additional empirical studies that compare the specific factors of the integrated delivery system model with other systems of care are needed to better understand the "system-level" factors that result in improved and/or diminished care delivery.

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

DOT National Transportation Integrated Search

2012-05-16

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

Drug delivery systems with modified release for systemic and biophase bioavailability.

PubMed

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

Systematic review: the applications of nanotechnology in gastroenterology.

PubMed

Brakmane, G; Winslet, M; Seifalian, A M

2012-08-01

Over the past 30 years, nanotechnology has evolved dramatically. It has captured the interest of variety of fields from computing and electronics to biology and medicine. Recent discoveries have made invaluable changes to future prospects in nanomedicine; and introduced the concept of theranostics. This term offers a patient specific 'two in one' modality that comprises of diagnostic and therapeutic tools. Not only nanotechnology has shown great impact on improvements in drug delivery and imaging techniques, but also there have been several ground-breaking discoveries in regenerative medicine. Gastroenterology invites multidisciplinary approach owing to high complexity of gastrointestinal (GI) system; it includes physicians, surgeons, radiologists, pharmacologists and many more. In this article, we concentrate on current developments in nano-gastroenterology. Literature search was performed using Web of Science and Pubmed search engines with terms--nanotechnology, nanomedicine and gastroenterology. Article search was concentrated on developments since 2005. We have described original and innovative approaches in gastrointestinal drug delivery, inflammatory disease and cancer-target treatments. Here, we have reviewed advances in GI imaging using nanoparticles as fluorescent contrast, and their potential for site-specific targeting. This review has also depicted various approaches and novel discoveries in GI regenerative medicine using nanomaterials for scaffold designs and induced pluripotent stem cells as cell source. Developments in nanotechnology have opened new range of possibilities to help our patients. This includes novel drug delivery vehicles, diagnostic tools for early and targeted disease detection and nanocomposite materials for tissue constructs to overcome cosmetic or physical disabilities. © 2012 Blackwell Publishing Ltd.

Blood-brain barrier transport of non-viral gene and RNAi therapeutics.

PubMed

Boado, Ruben J

2007-09-01

The development of gene- and RNA interference (RNAi)-based therapeutics represents a challenge for the drug delivery field. The global brain distribution of DNA genes, as well as the targeting of specific regions of the brain, is even more complicated because conventional delivery systems, i.e. viruses, have poor diffusion in brain when injected in situ and do not cross the blood-brain barrier (BBB), which is only permeable to lipophilic molecules of less than 400 Da. Recent advances in the "Trojan Horse Liposome" (THL) technology applied to the transvascular non-viral gene therapy of brain disorders presents a promising solution to the DNA/RNAi delivery obstacle. The THL is comprised of immunoliposomes carrying either a gene for protein replacement or small hairpin RNA (shRNA) expression plasmids for RNAi effect, respectively. The THL is engineered with known lipids containing polyethyleneglycol (PEG), which stabilizes its structure in vivo in circulation. The tissue target specificity of THL is given by conjugation of approximately 1% of the PEG residues to peptidomimetic monoclonal antibodies (MAb) that bind to specific endogenous receptors (i.e. insulin and transferrin receptors) located on both the BBB and the brain cellular membranes, respectively. These MAbs mediate (a) receptor-mediated transcytosis of the THL complex through the BBB, (b) endocytosis into brain cells and (c) transport to the brain cell nuclear compartment. The present review presents an overview of the THL technology and its current application to gene therapy and RNAi, including experimental models of Parkinson's disease and brain tumors.

Biodegradable thermoresponsive polymeric magnetic nanoparticles: a new drug delivery platform for doxorubicin

NASA Astrophysics Data System (ADS)

Andhariya, Nidhi; Chudasama, Bhupendra; Mehta, R. V.; Upadhyay, R. V.

2011-04-01

The use of nanoparticles as drug delivery systems for anticancer therapeutics has great potential to revolutionize the future of cancer therapy. The aim of this study is to construct a novel drug delivery platform comprising a magnetic core and biodegradable thermoresponsive shell of tri-block-copolymer. Oleic acid-coated Fe3O4 nanoparticles and hydrophilic anticancer drug "doxorubicin" are encapsulated with PEO-PLGA-PEO (polyethylene oxide-poly d, l lactide-co-glycolide-polyethylene oxide) tri-block-copolymer. Structural, magnetic, and physical properties of Fe3O4 core are determined by X-ray diffraction, vibrating sample magnetometer, and transmission electron microscopy techniques, respectively. The hydrodynamic size of composite nanoparticles is determined by dynamic light scattering and is found to be 36.4 nm at 25 °C. The functionalization of magnetic core with various polymeric chain molecules and their weight proportions are determined by Fourier transform infrared spectroscopy and thermogravimetric analysis, respectively. Encapsulation of doxorubicin into the polymeric magnetic nanoparticles, its loading efficiency, and kinetics of drug release are investigated by UV-vis spectroscopy. The loading efficiency of drug is 89% with a rapid release for the initial 7 h followed by the sustained release over a period of 36 h. The release of drug is envisaged to occur in response to the physiological temperature by deswelling of thermoresponsive PEO-PLGA-PEO block-copolymer. This study demonstrates that temperature can be exploited successfully as an external parameter to control the release of drug.

Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

PubMed

Debotton, Nir; Dahan, Arik

2017-01-01

Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.

Production of recombinant antigens and antibodies in Nicotiana benthamiana using 'magnifection' technology: GMP-compliant facilities for small- and large-scale manufacturing.

PubMed

Klimyuk, Victor; Pogue, Gregory; Herz, Stefan; Butler, John; Haydon, Hugh

2014-01-01

This review describes the adaptation of the plant virus-based transient expression system, magnICON(®) for the at-scale manufacturing of pharmaceutical proteins. The system utilizes so-called "deconstructed" viral vectors that rely on Agrobacterium-mediated systemic delivery into the plant cells for recombinant protein production. The system is also suitable for production of hetero-oligomeric proteins like immunoglobulins. By taking advantage of well established R&D tools for optimizing the expression of protein of interest using this system, product concepts can reach the manufacturing stage in highly competitive time periods. At the manufacturing stage, the system offers many remarkable features including rapid production cycles, high product yield, virtually unlimited scale-up potential, and flexibility for different manufacturing schemes. The magnICON system has been successfully adaptated to very different logistical manufacturing formats: (1) speedy production of multiple small batches of individualized pharmaceuticals proteins (e.g. antigens comprising individualized vaccines to treat NonHodgkin's Lymphoma patients) and (2) large-scale production of other pharmaceutical proteins such as therapeutic antibodies. General descriptions of the prototype GMP-compliant manufacturing processes and facilities for the product formats that are in preclinical and clinical testing are provided.

The impact of a preloaded intraocular lens delivery system on operating room efficiency in routine cataract surgery.

PubMed

Jones, Jason J; Chu, Jeffrey; Graham, Jacob; Zaluski, Serge; Rocha, Guillermo

2016-01-01

The aim of this study was to evaluate the operational impact of using preloaded intraocular lens (IOL) delivery systems compared with manually loaded IOL delivery processes during routine cataract surgeries. Time and motion data, staff and surgery schedules, and cost accounting reports were collected across three sites located in the US, France, and Canada. Time and motion data were collected for manually loaded IOL processes and preloaded IOL delivery systems over four surgery days. Staff and surgery schedules and cost accounting reports were collected during the 2 months prior and after introduction of the preloaded IOL delivery system. The study included a total of 154 routine cataract surgeries across all three sites. Of these, 77 surgeries were performed using a preloaded IOL delivery system, and the remaining 77 surgeries were performed using a manual IOL delivery process. Across all three sites, use of the preloaded IOL delivery system significantly decreased mean total case time by 6.2%-12.0% (P<0.001 for data from Canada and the US and P<0.05 for data from France). Use of the preloaded delivery system also decreased surgeon lens time, surgeon delays, and eliminated lens touches during IOL preparation. Compared to a manual IOL delivery process, use of a preloaded IOL delivery system for cataract surgery reduced total case time, total surgeon lens time, surgeon delays, and eliminated IOL touches. The time savings provided by the preloaded IOL delivery system provide an opportunity for sites to improve routine cataract surgery throughput without impacting surgeon or staff capacity.

Living in Health, Harmony, and Beauty: The Diné (Navajo) Hózhó Wellness Philosophy

PubMed Central

Koithan, Mary

2015-01-01

Hózhó is the complex wellness philosophy and belief system of the Diné (Navajo) people, comprised of principles that guide one's thoughts, actions, behaviors, and speech. The alignment of integrative nursing principles and the Hózhó Wellness Philosophy illustrates the power that integrative nursing offers as a meta-theoretical perspective that can transform our healthcare system so that it is inclusive and responsive to the needs of our varied populations. Integrative nursing offers the opportunity to re-introduce cultural wellness wisdom, such as Hózhó, as a means to improve whole-person/whole-systems wellbeing and resilience. Integrative nursing, through the acceptance and validation of indigenous health-sustaining wisdom, contributes to the delivery of effective, authentic, culturally tailored, whole-person/whole-system, patient-centered, relationship-based healthcare. Highlighting the Diné Hózhó philosophy re-introduces this philosophy to the Diné, other American Indian/Alaska Native nations, global indigenous cultures, and even nonindigenous people of the world as a means to promote and sustain global health and wellbeing. PMID:25984415

Multi-element fiber technology for space-division multiplexing applications.

PubMed

Jain, S; Rancaño, V J F; May-Smith, T C; Petropoulos, P; Sahu, J K; Richardson, D J

2014-02-24

A novel technological approach to space division multiplexing (SDM) based on the use of multiple individual fibers embedded in a common polymer coating material is presented, which is referred to as Multi-Element Fiber (MEF). The approach ensures ultralow crosstalk between spatial channels and allows for cost-effective ways of realizing multi-spatial channel amplification and signal multiplexing/demultiplexing. Both the fabrication and characterization of a passive 3-element MEF for data transmission, and an active 5-element erbium/ytterbium doped MEF for cladding-pumped optical amplification that uses one of the elements as an integrated pump delivery fiber is reported. Finally, both components were combined to emulate an optical fiber network comprising SDM transmission lines and amplifiers, and illustrate the compatibility of the approach with existing installed single-mode WDM fiber systems.

Air conditioning system

DOEpatents

Lowenstein, Andrew; Miller, Jeffrey; Gruendeman, Peter; DaSilva, Michael

2005-02-01

An air conditioner comprises a plurality of plates arranged in a successively stacked configuration with portions thereof having a spaced apart arrangement, and defining between successive adjacent pairs of plates at the spaced apart portions a first and second series of discrete alternating passages wherein a first air stream is passed through the first series of passages and a second air stream is passed through the second series of passages; and said stacked configuration of plates forming integrally therewith a liquid delivery means for delivering from a source a sufficient quantity of a liquid to the inside surfaces of the first series of fluid passages in a manner which provides a continuous flow of the liquid from a first end to a second end of the plurality of plates while in contact with the first air stream.

Supramolecularly Engineered Circular Bivalent Aptamer for Enhanced Functional Protein Delivery.

PubMed

Jiang, Ying; Pan, Xiaoshu; Chang, Jin; Niu, Weijia; Hou, Weijia; Kuai, Hailan; Zhao, Zilong; Liu, Ji; Wang, Ming; Tan, Weihong

2018-06-06

Circular bivalent aptamers (cb-apt) comprise an emerging class of chemically engineered aptamers with substantially improved stability and molecular recognition ability. Its therapeutic application, however, is challenged by the lack of functional modules to control the interactions of cb-apt with therapeutics. We present the design of a β-cyclodextrin-modified cb-apt (cb-apt-βCD) and its supramolecular interaction with molecular therapeutics via host-guest chemistry for targeted intracellular delivery. The supramolecular ensemble exhibits high serum stability and enhanced intracellular delivery efficiency compared to a monomeric aptamer. The cb-apt-βCD ensemble delivers green fluorescent protein into targeted cells with efficiency as high as 80%, or cytotoxic saporin to efficiently inhibit tumor cell growth. The strategy of conjugating βCD to cb-apt, and subsequently modulating the supramolecular chemistry of cb-apt-βCD, provides a general platform to expand and diversify the function of aptamers, enabling new biological and therapeutic applications.

FLITECAM: delivery and performance on SOFIA

NASA Astrophysics Data System (ADS)

Logsdon, Sarah E.; McLean, Ian S.; Becklin, E. E.; Hamilton, Ryan T.; Vacca, William D.; Waddell, Patrick

2016-08-01

We present a performance report for FLITECAM, a 1-5 μm imager and spectrograph, upon its acceptance and delivery to SOFIA (Stratospheric Observatory for Infrared Astronomy). FLITECAM has two observing configurations: solo configuration and "FLIPO" configuration, which is the co-mounting of FLITECAM with the optical instrument HIPO (PI E. Dunham, Lowell Observatory). FLITECAM was commissioned in the FLIPO configuration in 2014 and flew in the solo configuration for the first time in Fall 2015, shortly after its official delivery to SOFIA. Here we quantify FLITECAM's imaging and spectral performance in both configurations and discuss the science capabilities of each configuration, with examples from in-flight commissioning and early science data. The solo configuration (which comprises fewer warm optics) has better sensitivity at longer wavelengths. We also discuss the causes of excess background detected in the in-flight FLITECAM images at low elevations and describe the current plan to mitigate the largest contributor to this excess background.

Erythrocytes-based synthetic delivery systems: transition from conventional to novel engineering strategies.

PubMed

Bhateria, Manisha; Rachumallu, Ramakrishna; Singh, Rajbir; Bhatta, Rabi Sankar

2014-08-01

Erythrocytes (red blood cells [RBCs]) and artificial or synthetic delivery systems such as liposomes, nanoparticles (NPs) are the most investigated carrier systems. Herein, progress made from conventional approach of using RBC as delivery systems to novel approach of using synthetic delivery systems based on RBC properties will be reviewed. We aim to highlight both conventional and novel approaches of using RBCs as potential carrier system. Conventional approaches which include two main strategies are: i) directly loading therapeutic moieties in RBCs; and ii) coupling them with RBCs whereas novel approaches exploit structural, mechanical and biological properties of RBCs to design synthetic delivery systems through various engineering strategies. Initial attempts included coupling of antibodies to liposomes to specifically target RBCs. Knowledge obtained from several studies led to the development of RBC membrane derived liposomes (nanoerythrosomes), inspiring future application of RBC or its structural features in other attractive delivery systems (hydrogels, filomicelles, microcapsules, micro- and NPs) for even greater potential. In conclusion, this review dwells upon comparative analysis of various conventional and novel engineering strategies in developing RBC based drug delivery systems, diversifying their applications in arena of drug delivery. Regardless of the challenges in front of us, RBC based delivery systems offer an exciting approach of exploiting biological entities in a multitude of medical applications.

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

PubMed Central

Ko, Young Tag; Choi, Dong-Kug

2018-01-01

Solid lipid nanoparticle (SLN) delivery systems have a wide applicability in the delivery of phyto-bioactive compounds to treat various chronic diseases, including diabetes, cancer, obesity and neurodegenerative diseases. The multiple benefits of SLN delivery include improved stability, smaller particle size, leaching prevention and enhanced lymphatic uptake of the bioactive compounds through oral delivery. However, the burst release makes the SLN delivery systems inadequate for the oral delivery of various phyto-bioactive compounds that can treat such chronic diseases. Recently, the surface-modified SLN (SMSLN) was observed to overcome this limitation for oral delivery of phyto-bioactive compounds, and there is growing evidence of an enhanced uptake of curcumin delivered orally via SMSLNs in the brain. This review focuses on different SLN and SMSLN systems that are useful for oral delivery of phyto-bioactive compounds to treat various chronic diseases. PMID:29588585

Development and in vivo safety assessment of tenofovir-loaded nanoparticles-in-film as a novel vaginal microbicide delivery system.

PubMed

Machado, Alexandra; Cunha-Reis, Cassilda; Araújo, Francisca; Nunes, Rute; Seabra, Vítor; Ferreira, Domingos; das Neves, José; Sarmento, Bruno

2016-10-15

Topical pre-exposure prophylaxis (PrEP) with antiretroviral drugs holds promise in preventing vaginal transmission of HIV. However, significant biomedical and social issues found in multiple past clinical trials still need to be addressed in order to optimize protection and users' adherence. One approach may be the development of improved microbicide products. A novel delivery platform comprising drug-loaded nanoparticles (NPs) incorporated into a thin polymeric film base (NPs-in-film) was developed in order to allow the vaginal administration of the microbicide drug candidate tenofovir. The system was optimized for relevant physicochemical features and characterized for biological properties, namely cytotoxicity and safety in a mouse model. Tenofovir-loaded poly(lactic-co-glycolic acid) (PLGA)/stearylamine (SA) composite NPs with mean diameter of 127nm were obtained with drug association efficiency above 50%, and further incorporated into an approximately 115μm thick, hydroxypropyl methylcellulose/poly(vinyl alcohol)-based film. The system was shown to possess suitable mechanical properties for vaginal administration and to quickly disintegrate in approximately 9min upon contact with a simulated vaginal fluid (SVF). The original osmolarity and pH of SVF was not affected by the film. Tenofovir was also released in a biphasic fashion (around 30% of the drug in 15min, followed by sustained release up to 24h). The incorporation of NPs further improved the adhesive potential of the film to ex vivo pig vaginal mucosa. Cytotoxicity of NPs and film was significantly increased by the incorporation of SA, but remained at levels considered tolerable for vaginal delivery of tenofovir. Moreover, histological analysis of genital tissues and cytokine/chemokine levels in vaginal lavages upon 14days of daily vaginal administration to mice confirmed that tenofovir-loaded NPs-in-film was safe and did not induce any apparent histological changes or pro-inflammatory response. Overall, obtained data support that the proposed delivery system combining the use of polymeric NPs and a film base may constitute an exciting alternative for the vaginal administration of microbicide drugs in the context of topical PrEP. The development of nanotechnology-based microbicides is a recent but promising research field seeking for new strategies to circumvent HIV sexual transmission. Different reports detail on the multiple potential advantages of using drug nanocarriers for such purpose. However, one important issue being frequently neglected regards the development of vehicles for the administration of microbicide nanosystems. In this study, we propose and detail on the development of a nanoparticle-in-film system for the vaginal delivery of the microbicide drug candidate tenofovir. This is an innovative approach that, to our best knowledge, had never been tested for tenofovir. Results, including those from in vivo testing, sustain that the proposed system is safe and holds potential for further development as a vaginal microbicide product. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

PubMed

2005-03-01

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

Biomaterials for drug delivery systems.

PubMed

Buckles, R G

1983-01-01

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Rumen-stable delivery systems.

PubMed

Papas; Wu

1997-12-08

Ruminants have a distinct digestive system which serves a unique symbiotic relationship between the host animal and predominantly anaerobic rumen bacteria and protozoa. Rumen fermentation can be both beneficial by enabling utilization of cellulose and non-protein nitrogen and detrimental by reducing the nutritive value of some carbohydrates, high biological value proteins and by hydrogenating unsaturated lipids. In addition it can also result in the modification and inactivation of many pharmacologically active ingredients administered to the host animal via the oral route. The advances in ruminant nutrition and health demand a rumen-stable delivery system which can deliver the active ingredient post-ruminally while simultaneously meet efficacy, safety and cost criteria. In contrast to drug delivery systems for humans, the demand for low-cost has hindered the development of effective rumen-stable delivery systems. Historically, heat and chemical treatment of feed components, low solubility analogues or lipid-based formulations have been used to achieve some degree of rumen-stability, and products have been developed accordingly. Recently, a polymeric pH-dependent rumen-stable delivery system has been developed and commercialized. The rationale of this delivery system is based on the pH difference between ruminal and abomasal fluids. The delivery system is composed of a basic polymer, a hydrophobic substance and a pigment material. It can be applied as a coating to solid particles via a common encapsulation method such as air-suspension coating. In the future, the delivery system could be used to deliver micronutrients and pharmaceuticals post-ruminally to ruminant animals. A further possible application of the delivery system is that it could also be combined with other controlled delivery devices/systems in order to enhance slow release or to achieve targeted delivery needs for ruminants. This paper discusses the rumen protection and the abomasal release mechanism of the polymeric coating. It also reviews other rumen stable delivery systems and methods for evaluating their in vitro and in vivo performance.

Design strategies and applications of circulating cell-mediated drug delivery systems.

PubMed

Su, Yixue; Xie, Zhiwei; Kim, Gloria B; Dong, Cheng; Yang, Jian

2015-01-01

Drug delivery systems, particularly nanomaterial-based drug delivery systems, possess a tremendous amount of potential to improve diagnostic and therapeutic effects of drugs. Controlled drug delivery targeted to a specific disease is designed to significantly improve the pharmaceutical effects of drugs and reduce their side effects. Unfortunately, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even with the development of numerous surface markers and targeting modalities. Thus, alternative drug and nanomedicine targeting approaches are desired. Circulating cells, such as erythrocytes, leukocytes, and stem cells, present innate disease sensing and homing properties. Hence, using living cells as drug delivery carriers has gained increasing interest in recent years. This review highlights the recent advances in the design of cell-mediated drug delivery systems and targeting mechanisms. The approaches of drug encapsulation/conjugation to cell-carriers, cell-mediated targeting mechanisms, and the methods of controlled drug release are elaborated here. Cell-based "live" targeting and delivery could be used to facilitate a more specific, robust, and smart payload distribution for the next-generation drug delivery systems.

Project Delivery System Mode Decision Based on Uncertain AHP and Fuzzy Sets

NASA Astrophysics Data System (ADS)

Kaishan, Liu; Huimin, Li

2017-12-01

The project delivery system mode determines the contract pricing type, project management mode and the risk allocation among all participants. Different project delivery system modes have different characteristics and applicable scope. For the owners, the selection of the delivery mode is the key point to decide whether the project can achieve the expected benefits, it relates to the success or failure of project construction. Under the precondition of comprehensively considering the influence factors of the delivery mode, the model of project delivery system mode decision was set up on the basis of uncertain AHP and fuzzy sets, which can well consider the uncertainty and fuzziness when conducting the index evaluation and weight confirmation, so as to rapidly and effectively identify the most suitable delivery mode according to project characteristics. The effectiveness of the model has been verified via the actual case analysis in order to provide reference for the construction project delivery system mode.

Approaches to Neural Tissue Engineering Using Scaffolds for Drug Delivery

PubMed Central

Willerth, Stephanie M.; Sakiyama-Elbert, Shelly E.

2007-01-01

This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented. PMID:17482308

Modeling the Delivery Physiology of Distributed Learning Systems.

ERIC Educational Resources Information Center

Paquette, Gilbert; Rosca, Ioan

2003-01-01

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

Evaluation of plasma C-reactive protein levels in pregnant women with and without periodontal disease: A comparative study.

PubMed

Sharma, Anupriya; Ramesh, Amitha; Thomas, Biju

2009-09-01

Circulating C-reactive protein (CRP) levels are a marker of systemic inflammation and are associated with periodontal disease, a chronic bacterial infection associated with elevation of proinflammatory cytokines and prostaglandins. CRP has been associated with adverse pregnancy outcomes, including preterm delivery, preeclampsia, and intrauterine growth restriction. Furthermore, periodontal disease has been associated with increased risk of preterm low birth weight, low birth weight, and preterm birth. The present study was conducted to assess plasma CRP levels in pregnant women with and without periodontal disease; to evaluate the effect of periodontal therapy on the incidence of preterm delivery; and to compare the incidence of preterm delivery in pregnant women with and without periodontal disease. A total of 90 pregnant women aged between 18-35 years with gestational age between 12-28 weeks were recruited and divided into three equal groups (control group, study group, treatment group) of 30 each. Blood samples were taken for estimation of C-reactive protein levels from all groups at 12-20 weeks of gestation, determined using ultrasensitive turbidimetric immunoassay (QUANTIA-CRP US). The treatment group comprised plaque control, scaling, and root planning and daily rinsing with 0.2% chlorhexidine mouth before 28 weeks of gestation. The mean value of C-reactive protein levels in subjects with periodontal disease was higher compared to control group i.e., 1.20 +/- 0.247 mg/dl and 1.22 +/- 0.250 mg/dl, respectively, compared to 0.713 +/- 0.139 mg/ dl (P = 0.001). The mean value of CRP levels before treatment was greater than the mean value after treatment i.e., 1.22 +/- 0.25 compared to 0.84 +/- 0.189 (P < 0.001). The incidence of preterm delivery (< 37 weeks) was 31.7% in the periodontal disease group (study group) compared to 8.3% in the control group (P = 0.001). The incidence of preterm delivery in the treatment group was 15.0% compared to 31.7% in the nontreatment group (study group). The findings from the study suggest that periodontal disease in pregnant women is associated with increased C- reactive protein levels in early pregnancy, incidence of preterm delivery is higher in pregnant women with periodontal disease compared to healthy controls, periodontal therapy during pregnancy reduces plasma CRP levels and there is decrease in incidence of preterm delivery after periodontal therapy.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

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

2012-01-01

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

Micro injector sample delivery system for charged molecules

DOEpatents

Davidson, James C.; Balch, Joseph W.

1999-11-09

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

Prototype system of secure VOD

NASA Astrophysics Data System (ADS)

Minemura, Harumi; Yamaguchi, Tomohisa

1997-12-01

Secure digital contents delivery systems are to realize copyright protection and charging mechanism, and aim at secure delivery service of digital contents. Encrypted contents delivery and history (log) management are means to accomplish this purpose. Our final target is to realize a video-on-demand (VOD) system that can prevent illegal usage of video data and manage user history data to achieve a secure video delivery system on the Internet or Intranet. By now, mainly targeting client-server systems connected with enterprise LAN, we have implemented and evaluated a prototype system based on the investigation into the delivery method of encrypted video contents.

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2011 CFR

2011-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2010 CFR

2010-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2013 CFR

2013-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2014 CFR

2014-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2012 CFR

2012-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

Abnormal placental invasion--a novel approach to treatment case report and review.

PubMed

Ophir, Ella; Singer-Jordan, Jonathan; Odeh, Marwan; Hirch, Yael; Maksimovsky, Olga; Shaider, Oleg; Yvry, Simon; Solt, Ido; Bornstein, Jacob

2009-12-01

The incidence of abnormal placental invasion has increased 10-fold in the past 50 years, reflecting the increased number of cesarean sections performed. Management relies on accurate early diagnosis with appropriate perioperative multidisciplinary planning to anticipate and avoid massive obstetric hemorrhage at delivery. Women at risk should plan to deliver at an institution with appropriate expertise and resources for managing this condition. We report a case of placenta increta management comprising preoperative placement of a pelvic artery balloon catheter, prophylactic balloon occlusion after delivery of the fetus, and embolization-assisted resection of the invaded uterine wall. We review incidence, methods of prenatal diagnosis, risk factors, and management of abnormally invasive placenta.

Microbubble Compositions, Properties and Biomedical Applications

PubMed Central

Sirsi, Shashank

2010-01-01

Over the last decade, there has been significant progress towards the development of microbubbles as theranostics for a wide variety of biomedical applications. The unique ability of microbubbles to respond to ultrasound makes them useful agents for contrast ultrasound imaging, molecular imaging, and targeted drug and gene delivery. The general composition of a microbubble is a gas core stabilized by a shell comprised of proteins, lipids or polymers. Each type of microbubble has its own unique advantages and can be tailored for specialized functions. In this review, different microbubbles compositions and physiochemical properties are discussed in the context of current progress towards developing novel constructs for biomedical applications, with specific emphasis on molecular imaging and targeted drug/gene delivery. PMID:20574549

Rips, Currents and Snags: Investigating the Delivery of Educational Goals for Young Australians in the Region of Gippsland, Victoria

ERIC Educational Resources Information Center

Lynch, Timothy

2012-01-01

Monash University (Gippsland campus) is situated in Churchill, Latrobe Valley, located in central Gippsland, eastern Victoria. A large percentage of the Gippsland region comprises of a socio-economically disadvantaged population (Figure 1). In Semester One, 2011 as part of the Bachelor of Primary Education course at Monash, it was decided that a…

Cellulose binding domain fusion proteins

DOEpatents

Shoseyov, O.; Yosef, K.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

1998-02-17

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

The Development and Infrastructure Needs Required for Success--One College's Model: Online Nursing Education at Drexel University

ERIC Educational Resources Information Center

Cornelius, Fran; Glasgow, Mary Ellen Smith

2007-01-01

Technology's impact on the delivery of health care mandates that nursing faculty use all technologies at their disposal to better prepare students to work in technology-infused health care environments. Essential components of an infrastructure to grow technology-infused nursing education include a skilled team comprised of tech-savvy faculty and…

Methods of use of cellulose binding domain proteins

DOEpatents

Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

1997-09-23

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

Nucleic acids encoding a cellulose binding domain

DOEpatents

Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

1996-01-01

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

Nucleic acids encoding a cellulose binding domain

DOEpatents

Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

1996-03-05

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 15 figs.

Methods of use of cellulose binding domain proteins

DOEpatents

Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

1997-01-01

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

Development of a solid self-microemulsifying drug delivery system (SMEDDS) for solubility enhancement of naproxen.

PubMed

Čerpnjak, Katja; Zvonar, Alenka; Vrečer, Franc; Gašperlin, Mirjana

2015-01-01

Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement. The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and dissolution rate of naproxen. Various oils and co-surfactants in combination with Gelucire® 44/14 were evaluated during excipient selection study, solubility testing, and construction of (pseudo)ternary diagrams. The selected system was further evaluated for naproxen solubility, self-microemulsification ability, and in vitro dissolution of naproxen. In addition, its transformation into a solid SMEDDS by spray-drying using maltodextrin as a solid carrier was performed. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to evaluate the physical characteristics of the solid SMEDDS obtained. The selected formulation of SMEDDS was comprised of Miglyol 812®, Peceol™, Gelucire® 44/14, and Solutol® HS 15. The liquid and solid SMEDDS formed a microemulsion after dilution with comparable average droplet size and exhibited uniform droplet size distribution. In the solid SMEDDS, liquid SMEDDS was adsorbed onto the surface of maltodextrin and formed smooth granular particles with the encapsulated drug predominantly in a dissolved state and partially in an amorphous state. Overall, incorporation of naproxen in SMEDDS, either liquid or solid, resulted in improved solubility and dissolution rate compared to pure naproxen. This study indicates that a liquid and solid SMEDDS is a strategy for solubility enhancement in the future development of orally delivered dosage forms.

Analysing the Stewardship Function in Botswana’s Health System: Reflecting on the Past, Looking to the Future

PubMed Central

Seitio-Kgokgwe, Onalenna; Gauld, Robin DC; Hill, Philip C.; Barnett, Pauline

2016-01-01

Background: In many parts of the world, ongoing deficiencies in health systems compromise the delivery of health interventions. The World Health Organization (WHO) identified four functions that health systems need to perform to achieve their goals: Efforts to strengthen health systems focus on the way these functions are carried out. While a number of studies on health systems functions have been conducted, the stewardship function has received limited attention. In this article, we evaluate the extent to which the Botswana Ministry of Health (MoH) undertook its stewardship role. Methods: We used the WHO Health Systems Performance Assessment Frame (HSPAF) to guide analysis of the stewardship function of the Botswana’s MoH focusing on formulation of national health policies, exerting influence through health regulation, and coalition building. Data were abstracted from published and unpublished documents. We interviewed 54 key informants comprising staff of the MoH (N = 40) and stakeholder organizations (N = 14). Data from documents was analyzed through content analysis. Interviews were transcribed and analyzed through thematic analysis. Results: A lack of capacity for health policy development was identified. Significant policy gaps existed in some areas. Challenges were reported in policy implementation. While the MoH made efforts in developing various statutes that regulated different aspects of the health system, some gaps existed in the regulatory framework. Poor enforcement of legislation was a challenge. Although the MoH had a high number of stakeholders, the mechanisms for stakeholder engagement in the planning processes were weak. Conclusion: Problems in the exercise of the stewardship function posed challenges in ensuring accountability and limited the health system’s ability to benefit from its stakeholders. Ongoing efforts to establish a District Health System under control of the MoH, attempts to improve service delivery at a national level and political will to strengthen public-private engagement mechanisms are some of the prospects that can improve the MoH’s stewardship function. PMID:28005550

Emerging potential of stimulus-responsive nanosized anticancer drug delivery systems for systemic applications.

PubMed

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Madeshwaran, Thiagarajan; Hiep, Tran Tuan; Kandasamy, Umadevi; Oh, Kyung Taek; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2018-02-01

The development of novel drug delivery systems based on well-defined polymer therapeutics has led to significant improvements in the treatment of multiple disorders. Advances in material chemistry, nanotechnology, and nanomedicine have revolutionized the practices of drug delivery. Stimulus-responsive material-based nanosized drug delivery systems have remarkable properties that allow them to circumvent biological barriers and achieve targeted intracellular drug delivery. Specifically, the development of novel nanocarrier-based therapeutics is the need of the hour in managing complex diseases. In this review, we have briefly described the fundamentals of drug targeting to diseased tissues, physiological barriers in the human body, and the mechanisms/modes of drug-loaded carrier systems. To that end, this review serves as a comprehensive overview of the recent developments in stimulus-responsive drug delivery systems, with focus on their potential applications and impact on the future of drug delivery.

A polymer driveshaft for use in orbital and rotational atherectomy

NASA Astrophysics Data System (ADS)

Grothe, Preston Lee

Driveshafts used in atherectomy medical devices are often comprised of coiled or braided metal wires. These constructions are designed to tolerate delivery through tortuous vessels and can endure high speed rotation used during activation of the atherectomy treatment. This research investigated polymer driveshaft designs, which were comprised of polymer inner and outer layers, and coiled or braided stainless steel wires. The polymer driveshaft materials included polyimide, nylon 12, and polytetrafluoroethylene (PTFE). Mechanical testing of polymer driveshafts was conducted to determine material response in bending, tension, compression, and torsion. The polymer driveshaft test results were then compared with current coiled metal wire driveshaft constructions. The investigation identified polymer driveshaft options that could feasibly work in an atherectomy application.

Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.

PubMed

Cherniakov, Irina; Izgelov, Dvora; Barasch, Dinorah; Davidson, Elyad; Domb, Abraham J; Hoffman, Amnon

2017-11-28

Nowadays, therapeutic indications for cannabinoids, specifically Δ 9 -tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is that its composition of materials is approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (10.8mg, 10mg respectively) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has in serving as a standardized oral cannabinoid formulation. Moreover, the concept of improving oral bioavailability described here, can pave the way for other potential lipophilic active compounds requiring enhancement of their oral bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploration of a Doxorubicin-Polymer Conjugate in Lipid-Polymer Hybrid Nanoparticle Drug Delivery

NASA Astrophysics Data System (ADS)

Lough, Emily

Nanoparticle (NP) drug delivery is a major focus in the research community because of its potential to use existing drugs in safer and more effective ways. Chemotherapy encapsulation in NPs shields the drug from the rest of the body while it is within the NP, with less systemic exposure leading to fewer off-target effects of the drug. However, passive loading of drugs into NPs is a suboptimal method, often leading to burst release upon administration. This work explores the impact of incorporating the drug-polymer conjugate doxorubicin-poly (lactic-co-glycolic) acid (Dox-PLGA) into a lipid-polymer hybrid nanoparticle (LPN). The primary difference in using a drug-polymer conjugate for NP drug delivery is the drug's release kinetics. Dox-PLGA LPNs showed a more sustained and prolonged release profile over 28 days compared to LPNs with passively loaded, unconjugated doxorubicin. This sustained release translates to cytotoxicity; when systemic circulation was simulated using dialysis, Dox-PLGA LPNs retained their cytotoxicity at a higher level than the passively loaded LPNs. The in vivo implication of preserving cytotoxic potency through a slower release profile is that the majority of Dox delivered via Dox-PLGA LPNs will be kept within the LPN until it reaches the tumor. This will result in fewer systemic side effects and more effective treatments given the higher drug concentration at the tumor site. An intriguing clinical application of this drug delivery approach lies in using Dox-PLGA LPNs to cross the blood-brain barrier (BBB). The incorporation of Dox-PLGA is hypothesized to have a protective effect on the BBB as its slow release profile will prevent drug from harming the BBB. Using induced pluripotent stem cells differentiated to human brain microvascular endothelial cells that comprise the BBB, the Dox-PLGA LPNs were shown to be less destructive to the BBB than their passively loaded counterparts. Dox-PLGA LPNs showed superior cytotoxicity against plated tumor cells than the passively loaded Dox LPNs after passing through an in vitro transwell BBB model. Dox-PLGA LPNs and drug-polymer conjugates are exciting alternatives to passively loaded NPs and show strong clinical promise of a treatment that is more potent with fewer side effects and less frequent administration.

Development of a macrophage-targeting and phagocytosis-inducing bio-nanocapsule-based nanocarrier for drug delivery.

PubMed

Li, Hao; Tatematsu, Kenji; Somiya, Masaharu; Iijima, Masumi; Kuroda, Shun'ichi

2018-06-01

Macrophage hyperfunction or dysfunction is tightly associated with various diseases, such as osteoporosis, inflammatory disorder, and cancers. However, nearly all conventional drug delivery system (DDS) nanocarriers utilize endocytosis for entering target cells; thus, the development of macrophage-targeting and phagocytosis-inducing DDS nanocarriers for treating these diseases is required. In this study, we developed a hepatitis B virus (HBV) envelope L particle (i.e., bio-nanocapsule (BNC)) outwardly displaying a tandem form of protein G-derived IgG Fc-binding domain and protein L-derived IgG Fab-binding domain (GL-BNC). When conjugated with the macrophage-targeting ligand, mouse IgG2a (mIgG2a), the GL-BNC itself, and the liposome-fused GL-BNC (i.e., GL-virosome) spontaneously initiated aggregation by bridging between the Fc-binding domain and Fab-binding domain with mIgG2a. The aggregates were efficiently taken up by macrophages, whereas this was inhibited by latrunculin B, a phagocytosis-specific inhibitor. The mIgG2a-GL-virosome containing doxorubicin exhibited higher cytotoxicity toward macrophages than conventional liposomes and other BNC-based virosomes. Thus, GL-BNCs and GL-virosomes may constitute promising macrophage-targeting and phagocytosis-inducing DDS nanocarriers. We have developed a novel macrophage-targeting and phagocytosis-inducing bio-nanocapsule (BNC)-based nanocarrier named GL-BNC, which comprises a hepatitis B virus envelope L particle outwardly displaying protein G-derived IgG Fc- and protein L-derived IgG Fab-binding domains in tandem. The GL-BNC alone or liposome-fused form (GL-virosomes) could spontaneously aggregate when conjugated with macrophage-targeting IgGs, inducing phagocytosis by the interaction between IgG Fc of aggregates and FcγR on phagocytes. Thereby these aggregates were efficiently taken up by macrophages. GL-virosomes containing doxorubicin exhibited higher cytotoxicity towards macrophages than ZZ-virosomes and liposomes. Our results suggested that GL-BNCs and GL-virosomes would serve as promising drug delivery system nanocarriers for targeting delivery to macrophages. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

MEMS: Enabled Drug Delivery Systems.

PubMed

Cobo, Angelica; Sheybani, Roya; Meng, Ellis

2015-05-01

Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Technical and scale efficiency in the delivery of child health services in Zambia: results from data envelopment analysis

PubMed Central

Achoki, Tom; Hovels, Anke; Masiye, Felix; Lesego, Abaleng; Leufkens, Hubert; Kinfu, Yohannes

2017-01-01

Objective Despite tremendous efforts to scale up key maternal and child health interventions in Zambia, progress has not been uniform across the country. This raises fundamental health system performance questions that require further investigation. Our study investigates technical and scale efficiency (SE) in the delivery of maternal and child health services in the country. Setting The study focused on all 72 health districts of Zambia. Methods We compiled a district-level database comprising health outcomes (measured by the probability of survival to 5 years of age), health outputs (measured by coverage of key health interventions) and a set of health system inputs, namely, financial resources and human resources for health, for the year 2010. We used data envelopment analysis to assess the performance of subnational units across Zambia with respect to technical and SE, controlling for environmental factors that are beyond the control of health system decision makers. Results Nationally, average technical efficiency with respect to improving child survival was 61.5% (95% CI 58.2% to 64.8%), which suggests that there is a huge inefficiency in resource use in the country and the potential to expand services without injecting additional resources into the system. Districts that were more urbanised and had a higher proportion of educated women were more technically efficient. Improved cooking methods and donor funding had no significant effect on efficiency. Conclusions With the pressing need to accelerate progress in population health, decision makers must seek efficient ways to deliver services to achieve universal health coverage. Understanding the factors that drive performance and seeking ways to enhance efficiency offer a practical pathway through which low-income countries could improve population health without necessarily seeking additional resources. PMID:28057650

Innovation of novel 'Tab in Tab' system for release modulation of milnacipran HCl: optimization, formulation and in vitro investigations.

PubMed

Parejiya, Punit B; Barot, Bhavesh S; Patel, Hetal K; Shelat, Pragna K; Shukla, Arunkumar

2013-11-01

The study was aimed toward development of modified release oral drug delivery system for highly water soluble drug, Milnacipran HCl (MH). Novel Tablet in Tablet system (TITs) comprising immediate and extended release dose of MH in different parts was fabricated. The outer shell was composed of admixture of MH, lactose and novel herbal disintegrant obtained from seeds of Lepidium sativum. In the inner core, MH was matrixed with blend of hydrophilic (Benecel®) and hydrophobic (Compritol®) polymers. 3² full factorial design and an artificial neuron network (ANN) were employed for correlating effect of independent variables on dependent variables. The TITs were characterized for pharmacopoeial specifications, in vitro drug release, SEM, drug release kinetics and FTIR study. The release pattern of MH from batch A10 containing 25.17% w/w Benecel® and 8.21% w/w of Compritol® exhibited drug release pattern close proximal to the ideal theoretical profile (t(50%) = 5.92 h, t(75%) = 11.9 h, t(90%) = 18.11 h). The phenomenon of drug release was further explained by concept of percolation and the role of Benecel® and Compritol® in drug release retardation was studied. The normalized error obtained from ANN was less, compared with the multiple regression analysis, and exhibits the higher accuracy in prediction. The results of short-term stability study revealed stable chataracteristics of TITs. SEM study of TITs at different dissolution time points confirmed both diffusion and erosion mechanisms to be operative during drug release from the batch A10. Novel TITs can be a succesful once a day delivery system for highly water soluble drugs.

He Tamariki Kokoti Tau-Tackling Preterm: a data-linkage methodology to explore the clinical care pathway in preterm deliveries.

PubMed

Filoche, Sara; Cram, Fiona; Beard, Angela; Sim, Dalice; Geller, Stacie; Edmonds, Liza; Robson, Bridget; Lawton, Beverley

2018-05-21

Significant health inequities exist around maternal and infant health for Māori, the indigenous people of Aotearoa New Zealand - and in particular around a premature (preterm) delivery. Māori babies are more likely to be born preterm (8.1%, compared to an overall rate of 7.4%) and they are more likely to have a preterm death. An essential part of redressing these disparities is to examine the clinical care pathway and outcomes associated with preterm deliveries. This paper describes a protocol utilising national and local health collections to enable such a study. This is a retrospective cohort study comprising 5 years data pertaining to preterm deliveries from 2010 to 2014. These data are generated from linked national administrative and local health information collections to explore a range of neonatal outcomes and infant mortality in relation to the antenatal care pathway and known risk factors for preterm delivery. This study is being conducted within a Kaupapa Māori paradigm that dismisses victim blaming and seeks to intervene at structural levels to improve the health and wellbeing of Māori whānau (family). Our data-linkage methodology optimises the utility of New Zealand health collections to address a significant health issue. Our findings will fill the information gaps around the burden of preterm delivery by quantifying the incidence of preterm delivery and adverse neonatal and infant outcomes in Aotearoa New Zealand. It will explore access to evidenced based care including use of steroids before birth, and appropriate place of delivery. The results from this study will inform maternity care services to improve management of preterm deliveries - both locally and internationally. This in turn will improve the preterm sequela by reducing the long-term health burden and health inequities.

Intracellular trafficking of hybrid gene delivery vectors.

PubMed

Keswani, Rahul K; Lazebnik, Mihael; Pack, Daniel W

2015-06-10

Viral and non-viral gene delivery vectors are in development for human gene therapy, but both exhibit disadvantages such as inadequate efficiency, lack of cell-specific targeting or safety concerns. We have recently reported the design of hybrid delivery vectors combining retrovirus-like particles with synthetic polymers or lipids that are efficient, provide sustained gene expression and are more stable compared to native retroviruses. To guide further development of this promising class of gene delivery vectors, we have investigated their mechanisms of intracellular trafficking. Moloney murine leukemia virus-like particles (M-VLPs) were complexed with chitosan (Chi) or liposomes (Lip) comprising DOTAP, DOPE and cholesterol to form the hybrid vectors (Chi/M-VLPs and Lip/M-VLPs, respectively). Transfection efficiency and cellular internalization of the vectors were quantified in the presence of a panel of inhibitors of various endocytic pathways. Intracellular transport and trafficking kinetics of the hybrid vectors were dependent on the synthetic component and used a combination of clathrin- and caveolar-dependent endocytosis and macropinocytosis. Chi/M-VLPs were slower to transfect compared to Lip/M-VLPs due to the delayed detachment of the synthetic component. The synthetic component of hybrid gene delivery vectors plays a significant role in their cellular interactions and processing and is a key parameter for the design of more efficient gene delivery vehicles. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

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

A global health delivery framework approach to epilepsy care in resource-limited settings.

PubMed

Cochran, Maggie F; Berkowitz, Aaron L

2015-11-15

The Global Health Delivery (GHD) framework (Farmer, Kim, and Porter, Lancet 2013;382:1060-69) allows for the analysis of health care delivery systems along four axes: a care delivery value chain that incorporates prevention, diagnosis, and treatment of a medical condition; shared delivery infrastructure that integrates care within existing healthcare delivery systems; alignment of care delivery with local context; and generation of economic growth and social development through the health care delivery system. Here, we apply the GHD framework to epilepsy care in rural regions of low- and middle-income countries (LMIC) where there are few or no neurologists. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitivity Analysis of Algan/GAN High Electron Mobility Transistors to Process Variation

DTIC Science & Technology

2008-02-01

delivery system gas panel including both hydride and alkyl delivery modules and the vent/valve configurations [14...Reactor Gas Delivery Systems A basic schematic diagram of an MOCVD reactor delivery gas panel is shown in Figure 13. The reactor gas delivery...system, or gas panel , consists of a network of stainless steel tubing, automatic valves and electronic mass flow controllers (MFC). There are separate

An Application of Queues to Offensive Support Indirect Fire Weapons Systems

DTIC Science & Technology

2005-01-01

weapons systems capability is founded on delivery systems, operational procedures, ammunition and technologies from the 1960s. The changing nature of...fire away from busy delivery systems to less busy delivery systems by calculating the comparative estimation of busyness as given in equation (17... changes in the battlefield. Ideally, the delivery systems could be provided with 9 DSTO-TR-1662 Track of gun movements (100 cals-for-lire) 100 90 so 70 60

Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and Transdermal Application.

PubMed

Jain, Shashank; Patel, Niketkumar; Shah, Mansi K; Khatri, Pinak; Vora, Namrata

2017-02-01

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid-based delivery systems (vesicular carriers and lipid particulate systems) have been the most successful. Vesicular carriers consist of liposomes, ultradeformable liposomes, and ethosomes, while lipid particulate systems consist of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers. These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Current and emerging lipid-based systems for transdermal drug delivery.

PubMed

Singla, Sumeet K; Sachdeva, Vishal

2015-01-01

Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides.

PubMed

Batista, Patrícia; Castro, Pedro M; Madureira, Ana Raquel; Sarmento, Bruno; Pintado, Manuela

2018-03-01

Bioactive proteins and peptides have been used with either prophylactic or therapeutic purposes, presenting inherent advantages as high specificity and biocompatibility. Nanocarriers play an important role in the stabilization of proteins and peptides, offering enhanced buccal permeation and protection while crossing the gastrointestinal tract. Moreover, preparation of nanoparticles as oral delivery systems for proteins/peptides may include tailored formulation along with functionalization aiming bioavailability enhancement of carried proteins or peptides. Oral delivery systems, namely buccal delivery systems, represent an interesting alternative route to parenteric delivery systems to carry proteins and peptides, resulting in higher comfort of administration and, therefore, compliance to treatment. This paper outlines an extensive overview of the existing publications on proteins/peptides oral nanocarriers delivery systems, with special focus on buccal route. Manufacturing aspects of most commonly used nanoparticles for oral delivery (e.g. polymeric nanoparticles using synthetic or natural polymers and lipid nanoparticles) advantages and limitations and potential applications of nanoparticles as proteins/peptides delivery systems will also be thoroughly addressed. Copyright © 2018 Elsevier Inc. All rights reserved.

Exploring the nature of governance at the level of implementation for health system strengthening: the DIALHS experience.

PubMed

Scott, Vera; Schaay, Nikki; Olckers, Patti; Nqana, Nomsa; Lehmann, Uta; Gilson, Lucy

2014-09-01

Health system governance has been recognized as a critical element of the health system strengthening agenda. To date, health governance research often focuses at national or global levels, adopting a macro-perspective that deals with governance structures, forms and principles. Little attention has been given to a micro-perspective which recognizes the role of health system actors in governance, or to considering the operational level of the health system. This article presents a South African case study of an intervention to address conflict in roles and responsibilities between multiple actors supporting service delivery at the local level, and explores the broader insights this experience generates about the nature of local health system governance. In an embedded case study, action learning and reflection theory were used to design and implement the intervention. Data in this article were drawn from minutes, observations and recorded reflections of the meetings and workshops that comprised the intervention. A theoretical governance framework was used both to understand the context of the intervention and to analyse the dimensions of governance relevant in the experience. The study shows how, through action learning and reflection, local managers in two organizations came to understand how the higher level misalignment of organizational structures and processes imposed governance constraints on them, and to see the impact this had on their organizational relationships. By re-framing the conflict as organizational, they were then able to create opportunities for staff to understand their context and participate in negotiating principles for communication and collaborative work. The result reduced conflict between staff in the two organizations, leading to improved implementation of programme support. Strengthening relationships among those working at local level by building collaborative norms and values is an important part of local health system governance for improved service delivery by multiple actors. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

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

NASA Astrophysics Data System (ADS)

Binh, Le N.

2017-01-01

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

Exploring the nature of governance at the level of implementation for health system strengthening: the DIALHS experience

PubMed Central

Scott, Vera; Schaay, Nikki; Olckers, Patti; Nqana, Nomsa; Lehmann, Uta; Gilson, Lucy

2014-01-01

Health system governance has been recognized as a critical element of the health system strengthening agenda. To date, health governance research often focuses at national or global levels, adopting a macro-perspective that deals with governance structures, forms and principles. Little attention has been given to a micro-perspective which recognizes the role of health system actors in governance, or to considering the operational level of the health system. This article presents a South African case study of an intervention to address conflict in roles and responsibilities between multiple actors supporting service delivery at the local level, and explores the broader insights this experience generates about the nature of local health system governance. In an embedded case study, action learning and reflection theory were used to design and implement the intervention. Data in this article were drawn from minutes, observations and recorded reflections of the meetings and workshops that comprised the intervention. A theoretical governance framework was used both to understand the context of the intervention and to analyse the dimensions of governance relevant in the experience. The study shows how, through action learning and reflection, local managers in two organizations came to understand how the higher level misalignment of organizational structures and processes imposed governance constraints on them, and to see the impact this had on their organizational relationships. By re-framing the conflict as organizational, they were then able to create opportunities for staff to understand their context and participate in negotiating principles for communication and collaborative work. The result reduced conflict between staff in the two organizations, leading to improved implementation of programme support. Strengthening relationships among those working at local level by building collaborative norms and values is an important part of local health system governance for improved service delivery by multiple actors. PMID:25274641

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

PubMed

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

2014-01-01

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

Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review.

PubMed

Hadinoto, Kunn; Sundaresan, Ajitha; Cheow, Wean Sin

2013-11-01

Lipid-polymer hybrid nanoparticles (LPNs) are core-shell nanoparticle structures comprising polymer cores and lipid/lipid-PEG shells, which exhibit complementary characteristics of both polymeric nanoparticles and liposomes, particularly in terms of their physical stability and biocompatibility. Significantly, the LPNs have recently been demonstrated to exhibit superior in vivo cellular delivery efficacy compared to that obtained from polymeric nanoparticles and liposomes. Since their inception, the LPNs have advanced significantly in terms of their preparation strategy and scope of applications. Their preparation strategy has undergone a shift from the conceptually simple two-step method, involving preformed polymeric nanoparticles and lipid vesicles, to the more principally complex, yet easier to perform, one-step method, relying on simultaneous self-assembly of the lipid and polymer, which has resulted in better products and higher production throughput. The scope of LPNs' applications has also been extended beyond single drug delivery for anticancer therapy, to include combinatorial and active targeted drug deliveries, and deliveries of genetic materials, vaccines, and diagnostic imaging agents. This review details the current state of development for the LPNs preparation and applications from which we identify future research works needed to bring the LPNs closer to its clinical realization. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

PubMed

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-06-01

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

PubMed

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-08-11

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

Stabilization challenges and formulation strategies associated with oral biologic drug delivery systems.

PubMed

Truong-Le, Vu; Lovalenti, Phillip M; Abdul-Fattah, Ahmad M

2015-10-01

Delivery of proteins to mucosal tissues of GI tract typically utilize formulations which protect against proteolysis and target the mucosal tissues. Using case studies from literature and the authors' own work, the in-process stability and solid state storage stability of biopharmaceuticals formulated in delivery systems designed for oral delivery to the GI tract will be reviewed. Among the range of delivery systems, biodegradable polymer systems for protection and controlled release of proteins have been the most studied; hence these systems will be covered in greater depth. These delivery systems include polymeric biodegradable microspheres or nanospheres that contain proteins or vaccines, which are designed to reduce the number of administrations/inoculations and the total protein dose required to achieve the desired biological effect. Specifically, this review will include a landscape survey of the systems that have been studied, the manufacturing processes involved, stability through the manufacturing process, key pharmaceutical formulation parameters that impact stability of the encased proteins, and storage stability of the encapsulated proteins in these delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases.

PubMed

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H F; Karla, Pradeep K; Boddu, Sai H S

2018-02-27

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.

Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

PubMed Central

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H. F.; Karla, Pradeep K.; Boddu, Sai H. S.

2018-01-01

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed. PMID:29495528

Controlled Drug Delivery Using Microdevices

PubMed Central

Sanjay, Sharma T.; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

2016-01-01

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems. PMID:26813304

Controlled Drug Delivery Using Microdevices.

PubMed

Sanjay, Sharma T; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems.

Transdermal drug delivery

PubMed Central

Prausnitz, Mark R.; Langer, Robert

2009-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

An update on applications of nanostructured drug delivery systems in cancer therapy: a review.

PubMed

Aberoumandi, Seyed Mohsen; Mohammadhosseini, Majid; Abasi, Elham; Saghati, Sepideh; Nikzamir, Nasrin; Akbarzadeh, Abolfazl; Panahi, Yunes; Davaran, Soodabeh

2017-09-01

Cancer is a main public health problem that is known as a malignant tumor and out-of-control cell growth, with the potential to assault or spread to other parts of the body. Recently, remarkable efforts have been devoted to develop nanotechnology to improve the delivery of anticancer drug to tumor tissue as minimizing its distribution and toxicity in healthy tissue. Nanotechnology has been extensively used in the advance of new strategies for drug delivery and cancer therapy. Compared to customary drug delivery systems, nano-based drug delivery method has greater potential in different areas, like multiple targeting functionalization, in vivo imaging, extended circulation time, systemic control release, and combined drug delivery. Nanofibers are used for different medical applications such as drug delivery systems.

pH-sensitive nano-systems for drug delivery in cancer therapy.

PubMed

Liu, Juan; Huang, Yuran; Kumar, Anil; Tan, Aaron; Jin, Shubin; Mozhi, Anbu; Liang, Xing-Jie

2014-01-01

Nanotechnology has been widely used in the development of new strategies for drug delivery and cancer therapy. Compared to traditional drug delivery systems, nano-based drug delivery system have greater potential in a variety of areas, such as multiple targeting functionalization, in vivo imaging, combined drug delivery, extended circulation time, and systemic control release. Nano-systems incorporating stimulus-responsive materials have remarkable properties which allow them to bypass biological barriers and achieve targeted intracellular drug delivery. As a result of the active metabolism of tumor cells, the tumor microenvironment (TME) is highly acidic compared to normal tissues. pH-Sensitive nano-systems have now been developed in which drug release is specifically triggered by the acidic tumor environment. Studies have demonstrated that novel pH-sensitive drug delivery systems are capable of improving the efficiency of cancer treatment. A number of these have been translated from bench to clinical application and have been approved by the Food and Drug Administration (FDA) for treatment of various cancerous diseases. Herein, this review mainly focuses on pH-sensitive nano-systems, including advances in drug delivery, mechanisms of drug release, and possible improvements in drug absorption, with the emphasis on recent research in this field. With deeper understanding of the difference between normal and tumor tissues, it might be possible to design ever more promising pH-responsive nano-systems for drug delivery and cancer therapy in the near future. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Development of hyaluronic acid-Fe2O3 hybrid magnetic nanoparticles for targeted delivery of peptides.

PubMed

Kumar, Arun; Sahoo, Bishwabhusan; Montpetit, Alison; Behera, Sumita; Lockey, Richard F; Mohapatra, Shyam S

2007-06-01

Novel hybrid nanoparticles comprised of hyaluronic acid (HA) and iron oxide were synthesized and characterized for the first time with the average diameter of less than 160 nm. The iron oxide (Fe2O3) particles are hybridized between HA layers by electrostatic interactions between the positive surface charge of the Fe2O3 nanoparticles and the negative charge of the carboxylate groups of HA, forming a corral-like structure. The particles were also characterized by FTIR and NMR to verify the hybridization. The particles were tested for their ability to deliver peptides to the cells using HEK293 and A549 cells. Results show that these particles delivered peptides at about 100% level. These HA-iron oxide nanoparticles are expected to be useful in developing effective tissue and cell targeting systems.

KSC-00pp1737

NASA Image and Video Library

2000-11-14

Workers in the payload changeout room stand by as the doors open on the payload transport canister. Inside is the P6 integrated truss segment, which will fly on mission STS-97. The P6 comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

Leading a change process to improve health service delivery.

PubMed Central

Bahamon, Claire; Dwyer, Joseph; Buxbaum, Ann

2006-01-01

In the fields of health and development, donors channel multiple resources into the design of new practices and technologies, as well as small-scale programmes to test them. But successful practices are rarely scaled up to the level where they beneficially impact large, impoverished populations. An effective process for change is to use the experiences of new practices gained at the programme level for full-scale implementation. To make an impact, new practices need to be applied, and supported by management systems, at many organizational levels. At every level, potential implementers and likely beneficiaries must first recognize some characteristics that would benefit them in the new practices. An effective change process, led by a dedicated internal change agent, comprises several well-defined phases that successively broaden and institutionalize the use of new practices. PMID:16917654

A Novel Nonviral Gene Delivery System: Multifunctional Envelope-Type Nano Device

NASA Astrophysics Data System (ADS)

Hatakeyama, Hiroto; Akita, Hidetaka; Kogure, Kentaro; Harashima, Hideyoshi

In this review we introduce a new concept for developing a nonviral gene delivery system which we call "Programmed Packaging." Based on this concept, we succeeded in developing a multifunctional envelope-type nano device (MEND), which exerts high transfection activities equivalent to those of an adenovirus in a dividing cell. The use of MEND has been extended to in vivo applications. PEG/peptide/DOPE ternary conjugate (PPD)-MEND, a new in vivo gene delivery system for the targeting of tumor cells that dissociates surface-modified PEG in tumor tissue by matrix metalloproteinase (MMP) and exerts significant transfection activities, was developed. In parallel with the development of MEND, a quantitative gene delivery system, Confocal Image-assisted 3-dimensionally integrated quantification (CIDIQ), also was developed. This method identified the rate-limiting step of the nonviral gene delivery system by comparing it with adenoviral-mediated gene delivery. The results of this analysis provide a new direction for the development of rational nonviral gene delivery systems.

Multi-channel gas-delivery system

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

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

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

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

PubMed

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

2015-10-09

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

Handheld Delivery System for Modified Boron-Type Fire Extinguishment Agent

DTIC Science & Technology

1993-11-01

was to develop and test a handheld portable delivery system for use with the modified boron-type fire extinguishing agent for metal fires . B...BACKGROUND A need exists for an extinguishing agent and accompanying delivery system that are effective against complex geometry metal fires . A modified...agent and its delivery system have proven effective against complex geometry metal fires containing up to 200 pounds of magnesium metal. Further

Methods of detection using a cellulose binding domain fusion product

DOEpatents

Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

1999-01-05

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 34 figs.

Water-soluble carbon nanotube compositions for drug delivery and medicinal applications

DOEpatents

Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dmitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jr., Jodie L.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.; Milas, Zvonimir L.; Mason, Kathy A.; Milas, Luka

2014-07-22

Compositions comprising a plurality of functionalized carbon nanotubes and at least one type of payload molecule are provided herein. The compositions are soluble in water and PBS in some embodiments. In certain embodiments, the payload molecules are insoluble in water. Methods are described for making the compositions and administering the compositions. An extended release formulation for paclitaxel utilizing functionalized carbon nanotubes is also described.

Kits and methods of detection using cellulose binding domain fusion proteins

DOEpatents

Shoseyov, O.; Yosef, K.

1998-04-14

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

Kits and methods of detection using cellulose binding domain fusion proteins

DOEpatents

Shoseyov, Oded

1998-01-01

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

Transformations: Proceedings of the 2008 Annual International Conference of the Association of Tertiary Learning Advisors of Aotearoa/New Zealand (ATLAANZ) (Porirua, New Zealand, November 19-21, 2008). Volume 4

ERIC Educational Resources Information Center

Silvester, Mary, Ed.

2009-01-01

This volume comprises the refereed proceedings of the 2008 ATLAANZ (Association of Tertiary Learning Advisors of Aotearoa/New Zealand) conference, and explores strands of transformations--learning within cultural contexts, service delivery, student literacy and numeracy, graduate students and professional practice. In Chapter 1, Kay Hammond…

The Validity and Reliability of the Violence Risk Scale-Sexual Offender Version: Assessing Sex Offender Risk and Evaluating Therapeutic Change

ERIC Educational Resources Information Center

Olver, Mark E.; Wong, Stephen C. P.; Nicholaichuk, Terry; Gordon, Audrey

2007-01-01

The Violence Risk Scale-Sexual Offender version (VRS-SO) is a rating scale designed to assess risk and predict sexual recidivism, to measure and link treatment changes to sexual recidivism, and to inform the delivery of sexual offender treatment. The VRS-SO comprises 7 static and 17 dynamic items empirically or conceptually linked to sexual…

Methods of detection using a cellulose binding domain fusion product

DOEpatents

Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

1999-01-01

A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

Status of Statewide Career Information Delivery Systems.

ERIC Educational Resources Information Center

Dunn, Wynonia L.

Intended as a resource document as well as a status report on all the statewide career information delivery systems (CIDS) in operation, this report examines the status of 39 statewide information systems. (Career information delivery systems are computer-based systems that provide national, state, and local information to individuals who are in…

A Systems Approach to Nitrogen Delivery

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

Goins, Bobby

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should bemore » less frustration associated with the delivery process.« less

Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses.

PubMed

Ribeiro, Andreza Maria; Figueiras, Ana; Veiga, Francisco

2015-01-01

Conventional ophthalmic systems present very low corneal systemic bioavailability due to the nasolacrimal drainage and the difficulty to deliver the drug in the posterior segment of ocular tissue. For these reasons, recent advances have focused on the development of new ophthalmic drug delivery systems. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings in soft contact lenses (SCL) and the applications of novel pharmaceutical systems for ocular drug delivery. Among the new therapeutic approaches in ophthalmology, SCL are novel continuous-delivery systems, providing high and sustained levels of drugs to the cornea. The tendency of research in ophthalmic drug delivery systems development are directed towards a combination of several technologies (bio-inspired and molecular imprinting techniques) and materials (cyclodextrins, surfactants, specific monomers). There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but also at the same time slow down the clearance of the drug. Different materials can be applied during the development of contact lenses and can be combined with natural inspired strategies of drug immobilization and release, providing successful tools for ocular drug delivery systems.

Dual-Ligand Modified Polymer-Lipid Hybrid Nanoparticles for Docetaxel Targeting Delivery to Her2/neu Overexpressed Human Breast Cancer Cells.

PubMed

Yang, Zhe; Tang, Wenxin; Luo, Xingen; Zhang, Xiaofang; Zhang, Chao; Li, Hao; Gao, Di; Luo, Huiyan; Jiang, Qing; Liu, Jie

2015-08-01

In this study, a dual-ligand polymer-lipid hybrid nanoparticle drug delivery vehicle comprised of an anti-HER2/neu peptide (AHNP) mimic with a modified HIV-1 Tat (mTAT) was established for the targeted treatment of Her2/neu-overexpressing cells. The resultant dual-ligand hybrid nanoparticles (NPs) consisted of a poly(lactide-co-glycolide) core, a near 90% surface coverage of the lipid monolayer, and a 5.7 nm hydrated polyethylene glycol shell. Ligand density optimization study revealed that cellular uptake efficiency of the hybrid NPs could be manipulated by controlling the surface-ligand densities. Furthermore, the cell uptake kinetics and mechanism studies showed that the dual-ligand modifications of hybrid NPs altered the cellular uptake pathway from caveolae-mediated endocytosis (CvME) to the multiple endocytic pathways, which would significantly enhance the NP internalization. Upon the systemic investigation of the cellular uptake behavior of dual-ligand hybrid NPs, docetaxel (DTX), a hydrophobic anticancer drug, was successfully encapsulated into dual-ligand hybrid NPs with high drug loading for Her2/neu-overexpressing SK-BR-3 breast cancer cell treatment. The DTX-loaded dual-ligand hybrid NPs showed a decreased burst release and a more gradual sustained drug release property. Because of the synergistic effect of dual-ligand modification, DTX-loaded dual-ligand hybrid NPs exerted substantially better therapeutic potency against SK-BR-3 cancer cells than other NP formulations and free DTX drugs. These results demonstrate that the dual-ligand hybrid NPs could be a promising vehicle for targeted drug delivery to treat breast cancer.

Recent developments in leishmaniasis vaccine delivery systems.

PubMed

Bhowmick, Sudipta; Ali, Nahid

2008-07-01

The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

Target isolation system, high power laser and laser peening method and system using same

DOEpatents

Dane, C. Brent; Hackel, Lloyd A.; Harris, Fritz

2007-11-06

A system for applying a laser beam to work pieces, includes a laser system producing a high power output beam. Target delivery optics are arranged to deliver the output beam to a target work piece. A relay telescope having a telescope focal point is placed in the beam path between the laser system and the target delivery optics. The relay telescope relays an image between an image location near the output of the laser system and an image location near the target delivery optics. A baffle is placed at the telescope focal point between the target delivery optics and the laser system to block reflections from the target in the target delivery optics from returning to the laser system and causing damage.

Biodegradable polymers for targeted delivery of anti-cancer drugs.

PubMed

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

2016-06-01

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

Role of Components in the Formation of Self-microemulsifying Drug Delivery Systems.

PubMed

Gurram, A K; Deshpande, P B; Kar, S S; Nayak, Usha Y; Udupa, N; Reddy, M S

2015-01-01

Pharmaceutical research is focused in designing novel drug delivery systems to improve the bioavailability of poorly water soluble drugs. Self-microemulsifying drug delivery systems, one among the lipid-based dosage forms were proven to be promising in improving the oral bioavailability of such drugs by enhancing solubility, permeability and avoiding first-pass metabolism via enhanced lymphatic transport. Further, they have been successful in avoiding both inter and intra individual variations as well as the dose disproportionality. Aqueous insoluble drugs, in general, show greater solubility in lipid based excipients, and hence they are formulated as lipid based drug delivery systems. The extent of solubility of a hydrophobic drug in lipid excipients i.e. oil, surfactant and co-surfactant (components of self-microemulsifying drug delivery systems) greatly affects the drug loading and in producing stable self-microemulsifying drug delivery systems. The present review highlighted the influence of physicochemical factors and structural features of the hydrophobic drug on its solubility in lipid excipients and an attempt was made to explore the role of each component of self-microemulsifying drug delivery systems in the formation of stable microemulsion upon dilution.

Identification of siRNA delivery enhancers by a chemical library screen.

PubMed

Gilleron, Jerome; Paramasivam, Prasath; Zeigerer, Anja; Querbes, William; Marsico, Giovanni; Andree, Cordula; Seifert, Sarah; Amaya, Pablo; Stöter, Martin; Koteliansky, Victor; Waldmann, Herbert; Fitzgerald, Kevin; Kalaidzidis, Yannis; Akinc, Akin; Maier, Martin A; Manoharan, Muthiah; Bickle, Marc; Zerial, Marino

2015-09-18

Most delivery systems for small interfering RNA therapeutics depend on endocytosis and release from endo-lysosomal compartments. One approach to improve delivery is to identify small molecules enhancing these steps. It is unclear to what extent such enhancers can be universally applied to different delivery systems and cell types. Here, we performed a compound library screen on two well-established siRNA delivery systems, lipid nanoparticles and cholesterol conjugated-siRNAs. We identified fifty-one enhancers improving gene silencing 2-5 fold. Strikingly, most enhancers displayed specificity for one delivery system only. By a combination of quantitative fluorescence and electron microscopy we found that the enhancers substantially differed in their mechanism of action, increasing either endocytic uptake or release of siRNAs from endosomes. Furthermore, they acted either on the delivery system itself or the cell, by modulating the endocytic system via distinct mechanisms. Interestingly, several compounds displayed activity on different cell types. As proof of principle, we showed that one compound enhanced siRNA delivery in primary endothelial cells in vitro and in the endocardium in the mouse heart. This study suggests that a pharmacological approach can improve the delivery of siRNAs in a system-specific fashion, by exploiting distinct mechanisms and acting upon multiple cell types. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Advanced Drug Delivery Systems for Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs: A Review.

PubMed

Kumar, Lalit; Verma, Shivani; Singh, Mehakjot; Tamanna, Tamanna; Utreja, Puneet

2018-06-04

Transdermal route of delivery of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has several advantages over other routes like reduced adverse effects, less systemic absorption, and avoidance of first pass effect and degradation in the gastrointestinal tract (GIT). Transdermal route is also beneficial for drugs having a narrow therapeutic index. The skin acts as the primary barrier for transdermal delivery of various therapeutic molecules. Various advanced nanocarrier systems offer several advantages like improved dermal penetration along with an extended drug release profile due to their smaller size and high surface area. Various nanocarrier explored for transdermal delivery of NSAIDs are liposomes, niosomes, ethosomes, polymeric nanoparticles (NPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), dendrimers, nanosuspensions/nanoemulsion, and nanofibers Objectives: In the present review, our major aim was to explore the therapeutic potential of advanced nanocarrier systems enlisted above for transdermal delivery of NSAIDs. All literature search regarding advanced nanocarrier systems for transdermal delivery of NSAIDs was done using Google Scholar and Pubmed. Advanced nanocarrier have shown various advantages like reduced side effect, low dosing frequency, high skin permeation, and ease of application over conventional transdermal delivery systems of NSAIDs in various preclinical studies. However, clinical exploration of advanced nanocarrier systems for transdermal delivery of NSAIDs is still a challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Biopolymers as transdermal drug delivery systems in dermatology therapy.

PubMed

Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

2010-01-01

The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

Controlled drug delivery systems: past forward and future back.

PubMed

Park, Kinam

2014-09-28

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. Copyright © 2014 Elsevier B.V. All rights reserved.

Methods and metrics challenges of delivery-system research

PubMed Central

2012-01-01

Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned). This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not) into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1) modeling intervention context; (2) measuring readiness for change; (3) assessing intervention fidelity and sustainability; (4) assessing complex, multicomponent interventions; and (5) incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory) and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on February 16-17, 2011. The opinions in the paper are those of the author and do not represent the views or recommendations of AHRQ or the US Department of Health and Human Services.1 PMID:22409885

Assembling nanoparticle coatings to improve the drug delivery performance of lipid based colloids

NASA Astrophysics Data System (ADS)

Simovic, Spomenka; Barnes, Timothy J.; Tan, Angel; Prestidge, Clive A.

2012-02-01

Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.

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.

Systematic Review of the Impact of Cancer Survivorship Care Plans on Health Outcomes and Health Care Delivery.

PubMed

Jacobsen, Paul B; DeRosa, Antonio P; Henderson, Tara O; Mayer, Deborah K; Moskowitz, Chaya S; Paskett, Electra D; Rowland, Julia H

2018-05-18

Purpose Numerous organizations recommend that patients with cancer receive a survivorship care plan (SCP) comprising a treatment summary and follow-up care plans. Among current barriers to implementation are providers' concerns about the strength of evidence that SCPs improve outcomes. This systematic review evaluates whether delivery of SCPs has a positive impact on health outcomes and health care delivery for cancer survivors. Methods Randomized and nonrandomized studies evaluating patient-reported outcomes, health care use, and disease outcomes after delivery of SCPs were identified by searching MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library. Data extracted by independent raters were summarized on the basis of qualitative synthesis. Results Eleven nonrandomized and 13 randomized studies met inclusion criteria. Variability was evident across studies in cancer types, SCP delivery timing and method, SCP recipients and content, SCP-related counseling, and outcomes assessed. Nonrandomized study findings yielded descriptive information on satisfaction with care and reactions to SCPs. Randomized study findings were generally negative for the most commonly assessed outcomes (ie, physical, functional, and psychological well-being); findings were positive in single studies for other outcomes, including amount of information received, satisfaction with care, and physician implementation of recommended care. Conclusion Existing research provides little evidence that SCPs improve health outcomes and health care delivery. Possible explanations include heterogeneity in study designs and the low likelihood that SCP delivery alone would influence distal outcomes. Findings are limited but more positive for proximal outcomes (eg, information received) and for care delivery, particularly when SCPs are accompanied by counseling to prepare survivors for future clinical encounters. Recommendations for future research include focusing to a greater extent on evaluating ways to ensure SCP recommendations are subsequently acted on as part of ongoing care.

Ocular delivery systems for topical application of anti-infective agents.

PubMed

Duxfield, Linda; Sultana, Rubab; Wang, Ruokai; Englebretsen, Vanessa; Deo, Samantha; Rupenthal, Ilva D; Al-Kassas, Raida

2016-01-01

For the treatment of anterior eye segment infections using anti-infective agents, topical ocular application is the most convenient route of administration. However, topical delivery of anti-infective agents is associated with a number of problems and challenges owing to the unique structure of the eye and the physicochemical properties of these compounds. Topical ocular drug delivery systems can be classified into two forms: conventional and non-conventional. The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation resulting in low ocular bioavailability. Recently, attention has been focused on improving topical ocular delivery of anti-infective agents using advanced drug delivery systems. This review will focus on the challenges of efficient topical ocular delivery of anti-infective agents and will discuss the various types of delivery systems used to improve the treatment anterior segment infections.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Recent advances in oral pulsatile drug delivery.

PubMed

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

2009-01-01

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

Methods and practices to diversify cell-based products.

PubMed

Vertès, Alain A

2017-12-15

Medicinal signaling cell (MSC)-based products represent emerging treatments in various therapeutic areas including cardiometabolic, inflammation, autoimmunity, orthopedics, wound healing and oncology. Exploring innovation beyond minimally manipulated plastic-adherent ex vivo expanded allogeneic MSCs enables product delineation. Product delineation is on the critical path to maximize clinical benefits and market access. An innovation framework is presented here along various innovation dimensions comprising composition-of-matter by means of positive cell surface markers, formulation varying for example the cell dose or the preservation mode and medium, manufacturing to adapt the secretome of MSCs to the condition of interest, the mode of delivery and corresponding delivery devices, as well as molecular engineering and biomarkers. The rationale of the innovation space thus described applies generally to all cell-based therapies.

Drug nanosuspensions: a ZIP tool between traditional and innovative pharmaceutical formulations.

PubMed

Leone, Federica; Cavalli, Roberta

2015-01-01

A nanosuspension or nanocrystal suspension is a versatile formulation combining conventional and innovative features. It comprises 100% pure drug nanoparticles with sizes in the nano-scale range, generally stabilized by surfactants or polymers. Nanosuspensions are usually obtained in liquid media with bottom-up and top-down methods or by their combination. They have been designed to enhance the solubility, the dissolution rate and the bioavailability of drugs via various administration routes. Due to their small sizes, nanosuspensions can be also considered a drug delivery nanotechnology for the preparation of nanomedicine products. This review focuses on the state of the art of the nanocrystal-based formulation. It describes theory characteristics, design parameters, preparation methods, stability issues, as well as specific in vivo applications. Innovative strategies proposed to obtain nanomedicine formulation using nanocrystals are also reported. Many drug nanodelivery systems have been developed to increase the bioavailability of drugs and to decrease adverse side effects, but few can be industrially manufactured. Nanocrystals can close this gap by combining traditional and innovative drug formulations. Indeed, they can be used in many pharmaceutical dosage forms as such, or developed as new nano-scaled products. Engineered surface nanocrystals have recently been proposed as a dual strategy for stability enhancement and targeting delivery of nanocrystals.

CEBS: a comprehensive annotated database of toxicological data

PubMed Central

Lea, Isabel A.; Gong, Hui; Paleja, Anand; Rashid, Asif; Fostel, Jennifer

2017-01-01

The Chemical Effects in Biological Systems database (CEBS) is a comprehensive and unique toxicology resource that compiles individual and summary animal data from the National Toxicology Program (NTP) testing program and other depositors into a single electronic repository. CEBS has undergone significant updates in recent years and currently contains over 11 000 test articles (exposure agents) and over 8000 studies including all available NTP carcinogenicity, short-term toxicity and genetic toxicity studies. Study data provided to CEBS are manually curated, accessioned and subject to quality assurance review prior to release to ensure high quality. The CEBS database has two main components: data collection and data delivery. To accommodate the breadth of data produced by NTP, the CEBS data collection component is an integrated relational design that allows the flexibility to capture any type of electronic data (to date). The data delivery component of the database comprises a series of dedicated user interface tables containing pre-processed data that support each component of the user interface. The user interface has been updated to include a series of nine Guided Search tools that allow access to NTP summary and conclusion data and larger non-NTP datasets. The CEBS database can be accessed online at http://www.niehs.nih.gov/research/resources/databases/cebs/. PMID:27899660

KSC-00pp1734

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, moves higher toward the payload changeout room (PCR). The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure (RSS) (at left) that supports payload delivery at the pad. At right is Space Shuttle Endeavour with its orange external tank and solid rocket boosters showing behind it. When the RSS is closed around Endeavour, the P6 truss will be able to be moved into the orbiter’s payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC00pp1734

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, moves higher toward the payload changeout room (PCR). The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure (RSS) (at left) that supports payload delivery at the pad. At right is Space Shuttle Endeavour with its orange external tank and solid rocket boosters showing behind it. When the RSS is closed around Endeavour, the P6 truss will be able to be moved into the orbiter’s payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC00pp1735

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, is lifted higher toward the payload changeout room (PCR) above it. The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure (RSS) (at left) that supports payload delivery at the pad. At right is Space Shuttle Endeavour with its orange external tank and one solid rocket booster showing behind it. When the RSS is closed around Endeavour, the P6 truss will be moved into the orbiter’s payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC-00pp1733

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, is lifted toward the payload changeout room (PCR). The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure (RSS) (on the left) that supports payload delivery at the pad. At right is Space Shuttle Endeavour with its orange external tank and one solid rocket booster showing behind it. When the RSS is closed around Endeavour, the P6 truss will be able to be moved into the orbiter’s payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC00pp1733

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, is lifted toward the payload changeout room (PCR). The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure (RSS) (on the left) that supports payload delivery at the pad. At right is Space Shuttle Endeavour with its orange external tank and one solid rocket booster showing behind it. When the RSS is closed around Endeavour, the P6 truss will be able to be moved into the orbiter’s payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

KSC-00pp1735

NASA Image and Video Library

2000-11-14

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 39B, the payload transport canister, with the P6 integrated truss segment inside, is lifted higher toward the payload changeout room (PCR) above it. The PCR is the enclosed, environmentally controlled portion of the Rotating Service Structure (RSS) (at left) that supports payload delivery at the pad. At right is Space Shuttle Endeavour with its orange external tank and one solid rocket booster showing behind it. When the RSS is closed around Endeavour, the P6 truss will be moved into the orbiter’s payload bay. The P6, payload on mission STS-97, comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. Launch of STS-97 is scheduled for Nov. 30 at 10:06 p.m. EST

Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

NASA Astrophysics Data System (ADS)

Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong

2017-06-01

Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

Estimation of diffuse and point source microbial pollution in the ribble catchment discharging to bathing waters in the north west of England.

PubMed

Wither, A; Greaves, J; Dunhill, I; Wyer, M; Stapleton, C; Kay, D; Humphrey, N; Watkins, J; Francis, C; McDonald, A; Crowther, J

2005-01-01

Achieving compliance with the mandatory standards of the 1976 Bathing Water Directive (76/160/EEC) is required at all U.K. identified bathing waters. In recent years, the Fylde coast has been an area of significant investments in 'point source' control, which have not proven, in isolation, to satisfactorily achieve compliance with the mandatory, let alone the guide, levels of water quality in the Directive. The potential impact of riverine sources of pollution was first confirmed after a study in 1997. The completion of sewerage system enhancements offered the potential for the study of faecal indicator delivery from upstream sources comprising both point sources and diffuse agricultural sources. A research project to define these elements commenced in 2001. Initially, a desk study reported here, estimated the principal infrastructure contributions within the Ribble catchment. A second phase of this investigation has involved acquisition of empirical water quality and hydrological data from the catchment during the 2002 bathing season. These data have been used further to calibrate the 'budgets' and 'delivery' modelling and these data are still being analysed. This paper reports the initial desk study approach to faecal indicator budget estimation using available data from the sewerage infrastructure and catchment sources of faecal indicators.

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

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

Kang, Minjee; Lee, Byeongdu; Leal, Cecilia

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

Nanomedicine in the development of anti-HIV microbicides.

PubMed

das Neves, José; Nunes, Rute; Rodrigues, Francisca; Sarmento, Bruno

2016-08-01

Prevention plays an invaluable role in the fight against HIV/AIDS. The use of microbicides is considered an interesting potential approach for topical pre-exposure prophylaxis of HIV sexual transmission. The prospects of having an effective product available are expected to be fulfilled in the near future as driven by recent and forthcoming results of clinical trials. Different dosage forms and delivery strategies have been proposed and tested for multiple microbicide drug candidates presently at different stages of the development pipeline. One particularly interesting approach comprises the application of nanomedicine principles to the development of novel anti-HIV microbicides, but its implications to efficacy and safety are not yet fully understood. Nanotechnology-based systems, either presenting inherent anti-HIV activity or acting as drug nanocarriers, may significantly influence features such as drug solubility, stability of active payloads, drug release, interactions between active moieties and virus/cells, intracellular drug delivery, drug targeting, safety, antiviral activity, mucoadhesive behavior, drug distribution and tissue penetration, and pharmacokinetics. The present manuscript provides a comprehensive and holistic overview of these topics as relevant to the development of vaginal and rectal microbicides. In particular, recent advances pertaining inherently active microbicide nanosystems and microbicide drug nanocarriers are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Silica nanogelling of environment-responsive PEGylated polyplexes for enhanced stability and intracellular delivery of siRNA.

PubMed

Gouda, Noha; Miyata, Kanjiro; Christie, R James; Suma, Tomoya; Kishimura, Akihiro; Fukushima, Shigeto; Nomoto, Takahiro; Liu, Xueying; Nishiyama, Nobuhiro; Kataoka, Kazunori

2013-01-01

In this study, poly(ethylene glycol) (PEG)-block-polycation/siRNA complexes (PEGylated polyplexes) were wrapped with a hydrated silica, termed "silica nanogelling", in order to enhance their stability and functionality. Silica nanogelling was achieved by polycondensation of soluble silicates onto the surface of PEGylated polyplexes comprising a disulfide cross-linked core. Formation of silica nanogel layer on the PEGylated cross-linked polyplexes was confirmed by particle size increase, surface charge reduction, and elemental analysis of transmission electron micrographs. Silica nanogelling substantially improved polyplex stability against counter polyanion-induced dissociation under non-reductive condition, without compromising the reductive environment-responsive siRNA release triggered by disulfide cleavage. Silica nanogelling significantly enhanced the sequence-specific gene silencing activity of the polyplexes in HeLa cells without associated cytotoxicity, probably due lower endosomal entrapment (or lysosomal degradation) of delivered siRNA. The lower endosomal entrapment of the silica nanogel system could be explained by an accelerated endosomal escape triggered by deprotonated silanol groups in the silica (the proton sponge hypothesis) and/or a modulated intracellular trafficking, possibly via macropinocytosis, as evidenced by the cellular uptake inhibition assay. Henceforth, silica nanogelling of PEGylated siRNA polyplexes is a promising strategy for preparation of stable and functional siRNA delivery vehicles. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

DOE PAGES

Kang, Minjee; Lee, Byeongdu; Leal, Cecilia

2017-10-20

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

Fabrication, Characterization, and Biological Activity of Avermectin Nano-delivery Systems with Different Particle Sizes

NASA Astrophysics Data System (ADS)

Wang, Anqi; Wang, Yan; Sun, Changjiao; Wang, Chunxin; Cui, Bo; Zhao, Xiang; Zeng, Zhanghua; Yao, Junwei; Yang, Dongsheng; Liu, Guoqiang; Cui, Haixin

2018-01-01

Nano-delivery systems for the active ingredients of pesticides can improve the utilization rates of pesticides and prolong their control effects. This is due to the nanocarrier envelope and controlled release function. However, particles containing active ingredients in controlled release pesticide formulations are generally large and have wide size distributions. There have been limited studies about the effect of particle size on the controlled release properties and biological activities of pesticide delivery systems. In the current study, avermectin (Av) nano-delivery systems were constructed with different particle sizes and their performances were evaluated. The Av release rate in the nano-delivery system could be effectively controlled by changing the particle size. The biological activity increased with decreasing particle size. These results suggest that Av nano-delivery systems can significantly improve the controllable release, photostability, and biological activity, which will improve efficiency and reduce pesticide residues.

Including safety-net providers in integrated delivery systems: issues and options for policymakers.

PubMed

Witgert, Katherine; Hess, Catherine

2012-08-01

Health care reform legislation has spurred efforts to develop integrated health care delivery systems that seek to coordinate the continuum of health services. These systems may be of particular benefit to patients who face barriers to accessing care or have multiple health conditions. But it remains to be seen how safety-net providers, including community health centers and public hospitals--which have long experience in caring for these vulnerable populations--will be included in integrated delivery systems. This issue brief explores key considerations for incorporating safety-net providers into integrated delivery systems and discusses the roles of state and federal agencies in sup­porting and testing models of integrated care delivery. The authors conclude that the most important principles in creating integrated delivery systems for vulnerable populations are: (1) an emphasis on primary care; (2) coordination of all care, including behavioral, social, and public health services; and (3) accountability for population health outcomes.

Advances in bioresponsive closed-loop drug delivery systems.

PubMed

Yu, Jicheng; Zhang, Yuqi; Yan, Junjie; Kahkoska, Anna R; Gu, Zhen

2017-11-27

Controlled drug delivery systems are able to improve efficacy and safety of therapeutics by optimizing the duration and kinetics of release. Among them, closed-loop delivery strategies, also known as self-regulated administration, have proven to be a practical tool for homeostatic regulation, by tuning drug release as a function of biosignals relevant to physiological and pathological processes. A typical example is glucose-responsive insulin delivery system, which can mimic the pancreatic beta cells to release insulin with a proper dose at a proper time point by responding to plasma glucose levels. Similar self-regulated systems are also important in the treatment of other diseases including thrombosis and bacterial infection. In this review, we survey the recent advances in bioresponsive closed-loop drug delivery systems, including glucose-responsive, enzyme-activated, and other biosignal-mediated delivery systems. We also discuss the future opportunities and challenges in this field. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances of blood cell-based drug delivery systems.

PubMed

Sun, Yanan; Su, Jing; Liu, Geyi; Chen, Jianjun; Zhang, Xiumei; Zhang, Ran; Jiang, Minhan; Qiu, Mingfeng

2017-01-01

Blood cells, including erythrocytes, leukocytes and platelets are used as drug carriers in a wide range of applications. They have many unique advantages such as long life-span in circulation (especially erythrocytes), target release capacities (especially platelets), and natural adhesive properties (leukocytes and platelets). These properties make blood cell based delivery systems, as well as their membrane-derived carriers, far superior to other drug delivery systems. Despite the advantages, the further development of blood cell-based delivery systems was hindered by limitations in the source, storage, and mass production. To overcome these problems, synthetic biomaterials that mimic blood cell and nanocrystallization of blood cells have been developed and may represent the future direction for blood cell membrane-based delivery systems. In this paper, we review recent progress of the rising blood cell-based drug delivery systems, and also discuss their challenges and future tendency of development. Copyright © 2016. Published by Elsevier B.V.

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape.

PubMed

Zylberberg, Claudia; Matosevic, Sandro

2016-11-01

Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.

Starting time for induction of labor and the risk for night-time delivery.

PubMed

Thorsell, M; Lyrenäs, S; Andolf, E; Kaijser, M

2011-08-01

To analyze if starting time for labor induction affected the risk of night-time delivery, and to evaluate to what extent the risk was influenced by Bishop score at start of induction, mode of induction, and parity. A retrospective cohort study of women who delivered at Danderyd Hospital, Stockholm, Sweden, 2002-2006, comprising 1940 women induced by Dinoprostone (PGE(2)) or transcervical balloon catheter (BARD). Risks for night-time delivery were calculated as absolute risk and Odds Ratios by unconditional logistic regression using induction of labor in the morning as reference. For nulliparae with Bishop score 0-3 induced by BARD, odds ratios for night-time delivery were 0.42 (95% C.I. 0.19-0.93) and 0.09 (95% C.I. 0.02-0.47) when inductions started in the afternoon and evening, respectively, compared to inductions starting in the morning For multiparae, however, the risk of night-time delivery was highest if induction started in the evening. Compared to inductions started in the morning, odds ratios for night-time delivery were 3.53 (95% C.I. 2.57-4.83) and 8.49 (95% C.I. 4.45-16.19) for induction starting in the afternoon and evening, respectively. Starting time of labor induction affects the risk of giving birth at night. For nulliparae induced by BARD, starting the induction in the evening instead of during the day may reduce the number of night-time deliveries substantially. For multiparae, however, our data suggest that induction of labor should take place in the morning. Copyright © 2011 Elsevier B.V. All rights reserved.

Maternal and neonatal outcomes in women with colorectal endometriosis.

PubMed

Thomin, A; Belghiti, J; David, C; Marty, O; Bornes, M; Ballester, M; Roman, H; Daraï, E

2018-05-01

To evaluate delivery and neonatal outcomes in women with resected or in situ bowel endometriosis. Retrospective cohort study. France. Analysis of 72 pregnancies from 67 women followed for colorectal endometriosis from 2001 to 2014 in six centres including two university expert centres for endometriosis. Univariate analysis of maternal and neonatal outcomes. Routes for delivery and rate of complications. The colorectal surgery group comprised 41 women and the in situ colorectal group, 26 women. Overall, half of the women underwent caesarean section. A high incidence of postoperative complications (39%) was observed after caesarean section with no difference between the groups. Surgical difficulties at newborn extraction (22%) and postoperative complications (39%) occurred more often in women with anterior deep infiltrating endometriosis (respectively 63 versus 11%, P = 0.007 and 67% versus 26%, P = 0.046) independently of prior surgery for endometriosis. In the remaining half, vaginal delivery required an operative procedure in 28% of the women with a significant increase in postpartum complications compared with those who did not require a procedure (P = 0.001). Overall, the incidence of postpartum complications was lower after vaginal delivery (14%) than after caesarean section (39%) (P = 0.03). Pregnant women with colorectal endometriosis, irrespective of prior surgery, should be informed of the high risk of delivery by caesarean section. Vaginal delivery is preferrable in this setting because of the lower incidence of postpartum complications. Due to the incidence of postpartum complications whatever the route of delivery, women should receive level III maternal care. © 2016 Royal College of Obstetricians and Gynaecologists.

The preference of Iranian women to have normal vaginal or cesarean deliveries

PubMed Central

Maharlouei, Najmeh; Rezaianzadeh, Abbas; Hesami, Elham; Moradi, Fariba; Mazloomi, Ezat; Joulaei, Hassan; Khodayari, Mohammad; Lankarani, Kamran B.

2013-01-01

Background: The cesarean section (C-section) has higher risk compared to normal vaginal delivery (NVD). The aim of this population-based study was to evaluate the frequency of mothers’ tendency toward the mode of delivery and the factors that can affect this inclination. Materials and Methods: This cross-sectional study was conducted from August 2011 to June 2012 in Fars Province, Iran, and comprised mothers in their 20th to 30th weeks of pregnancy. A questionnaire was designed to include, sociodemographic information, maternal knowledge, main sources of knowledge, attitude of the mother, husband, parents, close friends, and gynecologist, regarding the route of delivery, convenience factors, and barriers to choosing NVD, and mother's preference for the route of delivery. Results: Of 6921 participants, 2197 (31.7%) preferred C-section and 4308 (62.2%) favored NVD while 416 (6%) had no idea regarding the preferred route of delivery. Score of knowledge in 904 (13.1%) participants was zero, and 1261 women (18.2%) achieved an acceptable level of knowledge. Using binary logistic regression, positive history of previous abortion and/or infertility, higher education level of mother and husband, mother's unacceptable level of knowledge regarding complications of C-section, and mother's and husband's positive attitude toward C-section were determinant factors in choosing C-section as a preferred route of delivery. Conclusion: Appropriate measures should be taken to raise awareness and knowledge of mothers and all families about complications of the C-section. Establishment of clinics for painless NVD and assuring mothers of benefits and lower complications of NVD can reduce the tendency for C-sections. PMID:24523780

Noninvasive ocular drug delivery: potential transcorneal and other alternative delivery routes for therapeutic molecules in glaucoma.

PubMed

Foldvari, Marianna

2014-01-01

Drug delivery to the eye is made difficult by multiple barriers (such as the tear film, cornea, and vitreous) between the surface of the eye and the treatment site. These barriers are difficult to surmount for the purposes of drug delivery without causing toxicity. Using nanotechnology tools to control, manipulate, and study delivery systems, new approaches to delivering drugs, genes, and antigens that are effective and safe can be developed. Topical administration to the ocular surface would be the safest method for delivery, as it is noninvasive and painless compared with other delivery methods. However, there is only limited success using topical delivery methods, especially for gene therapy. Current thinking on treatments of the future enabled by nanodelivery systems and the identification of target specificity parameters that require deeper understanding to develop successful topical delivery systems for glaucoma is highlighted.

Recent advances of controlled drug delivery using microfluidic platforms.

PubMed

Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

2018-03-15

Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery.

PubMed

Shorter, Susan A; Gollings, Alexander S; Gorringe-Pattrick, Monique A M; Coakley, J Emma; Dyer, Paul D R; Richardson, Simon C W

2017-05-01

The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for 'drug' delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the 'PEG dilemma', balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem. Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking. Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic 'helpers' or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic.

Some engineering aspects of insulin delivery systems.

PubMed

Spencer, W J; Bair, R E; Carlson, G A; Love, J T; Urenda, R S; Eaton, R P; Schade, D S

1980-01-01

The characteristics of electronically controlled insulin delivery systems are presented. Early experiments with an external system have shown promise in providing improved glycemic control over conventional methods of single or multiple subcutaneous insulin injections. The encouraging results with external insulin delivery systems have led to the development and early testing in dogs of an implantable system with remote controls to permit variable insulin flow rates. A number of questions remain to be answered before widespread experimentation with external and implanted insulin delivery systems is possible. There appears to be no major development problems with the engineering aspects of such systems.

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

PubMed Central

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

2015-01-01

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828

Factor structure of the geriatric care environment scale.

PubMed

Kim, Hongsoo; Capezuti, Elizabeth; Boltz, Marie; Fairchild, Susan; Fulmer, Terry; Mezey, Mathy

2007-01-01

Older adults comprise approximately 60% of all adult, nonobstetric hospital admissions. Nurses Improving Care for Health System Elders (NICHE) is a national program aimed at system improvement to achieve patient-centered care for older adults. The NICHE hospitals use the Geriatric Institutional Assessment Profile (GIAP) to assess their institutional readiness to provide quality care to older adults and to document improvement in geriatric care delivery. To explore the factorial structure of the 28-item Geriatric Care Environment Scale (GCES) of the GIAP, test its validity with a sample of staff registered nurses (RNs), and evaluate its invariance across 4 groups of RNs who worked at 4 different types of hospitals. Staff RNs (N = 9,400) at 71 acute hospitals, who responded to the GIAP from 1999 to 2004, were split randomly into 2 groups for cross-validation. A 3-step data analysis was completed. The a priori factor structure was developed using exploratory factor analysis. The obtained factor model was validated, and its invariance by types of hospitals was examined by confirmatory factor analyses. The GCES is internally consistent (Cronbach's alpha = .93) and accounts for approximately 55% of the total variance. The 4 factors extracted from the exploratory factor analysis are Aging-Sensitive Care Delivery, Resource Availability, Institutional Values Regarding Older Adults and Staff, and Capacity for Collaboration. The 4-factor structured model is validated in a half-randomly selected sample (normed fit index [NFI] = .931, nonnormed fit index [NNFI] = .933, comparative fit index [CFI] = .939, root-mean-square error of approximation [RMSEA] = .058) and does not vary significantly across the 4 groups of RNs who worked at the 4 different types of hospitals (NFI = .969, NNFI = .975, CFI = .976, RMSEA = .027). The GCES is a reliable measure of RN perception of how care provided to older adults reflects age-sensitive principles and the organizational practice environment that supports or hinders care delivery.

Nomenclature associated with chemical characterization of and compatibility evaluations for medical product delivery systems.

PubMed

Jenke, Dennis R

2003-01-01

Delivery systems are used to store, contain, and/or administer liquid pharmaceutical products. Gaining an understanding of the chemical composition of such a delivery system is necessary with respect to effective system development, registration, and production. Additionally, the ability of the delivery system to impact the chemical composition of the contacted product may define the safety and/or efficacy of the product. Assessing the compatibility of the delivery system and the product is thus both necessary and desirable. The nomenclature associated with compatibility assessments has not been standardized, oftimes leading to conflicting or confusing information. This manuscript puts forth a nomenclature which classifies those chemical entities which participate in the system/product interaction and delineates the various extraction strategies which may be used in compatibility assessments.

Enhanced stability and permeation potential of nanoemulsion containing sefsol-218 oil for topical delivery of amphotericin B.

PubMed

Hussain, Afzal; Samad, Abdus; Singh, Sandeep Kumar; Ahsan, Mohd Neyaz; Faruk, Abdul; Ahmed, Farhan Jalees

2015-05-01

To characterize the enhanced stability and permeation potential of amphotericin B nanoemulsion comprising sefsol-218 oil at varying pH and temperature of aqueous continuous phase. Several batches of amphotericin B loaded nanoemulsion were prepared and evaluated for their physical and chemical stability at different pH and temperature. Also, a comparative study of ex vivo drug permeation across the albino rat skin was investigated with commercial Fungisome® and drug solution at 37 °C for 24 h. The extent of drug penetrated through the rat skin was thereby evaluated using the confocal laser scanning microscopy (CLSM). The optimized nanoemulsion demonstrated the highest flux rate 17.85 ± 0.5 µg/cm(2)/h than drug solution (5.37 ± 0.01 µg/cm(2)/h) and Fungisome® (7.97 ± 0.01 µg/cm(2)/h). Ex vivo drug penetration mechanism from the developed formulations at pH 6.8 and pH 7.4 of aqueous phase pH using the CLSM revealed enhanced penetration. Ex vivo drug penetration studies of developed formulation comprising of CLSM revealed enhanced penetration in aqueous phase at pH 6.8 and 7.4. The aggregation behavior of nanoemulsion at both the pH was found to be minimum and non-nephrotoxic. The stability of amphotericin B was obtained in terms of pH, optical density, globular size, polydispersity index and zeta potential value at different temperature for 90 days. The slowest drug degradation was observed in aqueous phase at pH 7.4 with shelf life 20.03-folds higher when stored at 4 °C (3.8 years) and 5-fold higher at 25 °C (0.951 years) than at 40 °C. The combined results suggested that nanoemulsion may hold an alternative for enhanced and sustained topical delivery system for amphotericin B.

Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

PubMed

Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

2016-09-01

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

PubMed Central

Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

2016-01-01

Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

PubMed Central

Shrivastav, Anupama; Kim, Hae-Yeong; Kim, Young-Rok

2013-01-01

Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system. PMID:23984383

Permeation enhancer strategies in transdermal drug delivery.

PubMed

Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

2016-01-01

Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

Functionalized and graft copolymers of chitosan and its pharmaceutical applications.

PubMed

Bhavsar, Chintan; Momin, Munira; Gharat, Sankalp; Omri, Abdelwahab

2017-10-01

Chitosan is the second most abundant natural polysaccharide. It belongs a family of polycationic polymers comprised of repetitive units of glucosamine and N-acetylglucosamine. Its biodegradability, nontoxicity, non-immunogenicity and biocompatibility along with properties like mucoadhesion, fungistatic and bacteriogenic have made chitosan an appreciated polymer with numerous applications in the pharmaceutical, comestics and food industry. However, the limited solubility of chitosan at alkaline and neutral pH limits its widespread commercial use. This can be circumvented by fabrication of chitosan by graft copolymerization with acyl, alkyl, monomeric and polymeric moieties. Areas covered: Modifications like quarterization, thiolation, acylation and grafting result in copolymers with higher mucoadhesion strength, increased hydrophobic interactions (advantageous in hydrophobic drug entrapment), and increased solubility in alkaline pH, the ability for adsorption of metal ions, protein and peptide delivery and nutrient delivery. Insights on methods of polymerization, including atomic transfer radical polymerization and click chemistry are discussed. Applications of such modified chitosan copolymers in medical and surgical, and drug delivery, including nasal, oral and buccal delivery have also been covered. Expert opinion: Despite a number of successful investigations, commercialization of chitosan copolymers still remains a challenge. Further advancements in polymerization techniques may address the unmet needs of the healthcare industry.

Examination of the association between male gender and preterm delivery.

PubMed

Brettell, Rachel; Yeh, Peter S; Impey, Lawrence W M

2008-12-01

To examine possible reasons why a male fetus constitutes a risk factor for preterm delivery. Retrospective study of deliveries from hospital database in a UK teaching hospital. The population comprised all deliveries >23 weeks over an 11-year period, excluding multiples, terminations and pregnancies with major abnormalities including indeterminate gender. Obstetric variables and outcomes were initially compared in male and female babies for preterm births in different gestation bands, extreme (<28 weeks), severe (29-32 weeks) and moderate (33-36 weeks). For each, the odds ratios with 95% confidence intervals for preterm delivery were calculated. Then, using binary logistic regression with adjusted odds ratios with 95% confidence intervals, putative causal pathways that might explain the male excess were tested. 75,725 deliveries occurred, of which 4003 (5.3%) were preterm. Males delivered preterm more frequently (OR 1.13, 95% CI 1.06-1.20). This was due to spontaneous (OR 1.30, 95% CI 1.19-1.42) but not iatrogenic (OR 0.96, 95% CI 0.87-1.05) preterm birth. There was an increased risk of pre eclampsia among preterm females. Although males were larger, and male pregnancies were more frequently nulliparous and affected by some other obstetric complications (abruption, urinary tract infection), these did not account for their increased risk. Any effect of growth restriction could not be properly determined. Being male carries an increased risk of spontaneous but not iatrogenic preterm birth. The reasons behind this remain obscure.

Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation

PubMed Central

Burke, Caitlin W.; Price, Richard J.

2010-01-01

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas. PMID:21206463

Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

PubMed

Burke, Caitlin W; Price, Richard J

2010-12-15

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

A systematic review and meta-analysis of velamentous cord insertion among singleton pregnancies and the risk of preterm delivery.

PubMed

de Los Reyes, Samantha; Henderson, Janice; Eke, Ahizechukwu C

2018-03-23

Observational studies have reported varying results about the association of velamentous cord insertion (VCI) with adverse pregnancy outcomes. To evaluate the risk of preterm delivery among singleton pregnancies complicated by VCI. Various databases were searched for English-language articles published up to February, 28, 2017, using keywords including VCI; abnormal placentation; abnormal cord insertions; adverse perinatal outcomes; and preterm birth. Outcome measures included preterm delivery; pre-eclampsia; cesarean delivery; fetal demise in utero (FDIU); and small for gestational age (SGA). Only studies involving VCI were included in the meta-analysis. Analyses were performed using RevMan version 5.3.5 (The Nordic Cochrane Centre, Copenhagen, Denmark). There were six studies included in the analysis. The VCI and control groups comprised 16 295 and 1 366 485 women, respectively. An increased incidence of preterm delivery was found for the VCI group compared with the control group (11.8% vs 7.0%; adjusted odds ratio [aOR] 1.95, 95% confidence interval [CI] 1.85-2.04). A diagnosis of VCI was also associated with cesarean delivery (aOR 1.17, 95% CI 1.12-1.23), SGA (aOR 1.93, 95% CI 1.83-2.04), and FDIU (aOR 3.96, 95% CI 3.21-4.89). The presence of VCI was associated with adverse pregnancy outcomes. © 2018 International Federation of Gynecology and Obstetrics.

Reasons for home delivery and use of traditional birth attendants in rural Zambia: a qualitative study.

PubMed

Sialubanje, Cephas; Massar, Karlijn; Hamer, Davidson H; Ruiter, Robert A C

2015-09-11

Despite the policy change stopping traditional birth attendants (TBAs) from conducting deliveries at home and encouraging all women to give birth at the clinic under skilled care, many women still give birth at home and TBAs are essential providers of obstetric care in rural Zambia. The main reasons for pregnant women's preference for TBAs are not well understood. This qualitative study aimed to identify reasons motivating women to giving birth at home and seek the help of TBAs. This knowledge is important for the design of public health interventions focusing on promoting facility-based skilled birth attendance in Zambia. We conducted ten focus group discussions (n = 100) with women of reproductive age (15-45 years) in five health centre catchment areas with the lowest institutional delivery rates in the district. In addition, a total of 30 in-depth interviews were conducted comprising 5 TBAs, 4 headmen, 4 husbands, 4 mothers, 4 neighbourhood health committee (NHC) members, 4 community health workers (CHWs) and 5 nurses. Perspectives on TBAs, the decision-making process regarding home delivery and use of TBAs, and reasons for preference of TBAs and their services were explored. Our findings show that women's lack of decision- making autonomy regarding child birth, dependence on the husband and other family members for the final decision, and various physical and socioeconomic barriers including long distances, lack of money for transport and the requirement to bring baby clothes and food while staying at the clinic, prevented them from delivering at a clinic. In addition, socio-cultural norms regarding childbirth, negative attitude towards the quality of services provided at the clinic, made most women deliver at home. Moreover, most women had a positive attitude towards TBAs and perceived them to be respectful, skilled, friendly, trustworthy, and available when they needed them. Our findings suggest a need to empower women with decision-making skills regarding childbirth and to lower barriers that prevent them from going to the health facility in time. There is also need to improve the quality of existing facility-based delivery services and to strengthen linkages between TBAs and the formal health system.

Basics and recent advances in peptide and protein drug delivery

PubMed Central

Bruno, Benjamin J; Miller, Geoffrey D; Lim, Carol S

2014-01-01

While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed. PMID:24228993

Technology Roadmap Instrumentation, Control, and Human-Machine Interface to Support DOE Advanced Nuclear Energy Programs

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

Donald D Dudenhoeffer; Burce P Hallbert

Instrumentation, Controls, and Human-Machine Interface (ICHMI) technologies are essential to ensuring delivery and effective operation of optimized advanced Generation IV (Gen IV) nuclear energy systems. In 1996, the Watts Bar I nuclear power plant in Tennessee was the last U.S. nuclear power plant to go on line. It was, in fact, built based on pre-1990 technology. Since this last U.S. nuclear power plant was designed, there have been major advances in the field of ICHMI systems. Computer technology employed in other industries has advanced dramatically, and computing systems are now replaced every few years as they become functionally obsolete. Functionalmore » obsolescence occurs when newer, more functional technology replaces or supersedes an existing technology, even though an existing technology may well be in working order.Although ICHMI architectures are comprised of much of the same technology, they have not been updated nearly as often in the nuclear power industry. For example, some newer Personal Digital Assistants (PDAs) or handheld computers may, in fact, have more functionality than the 1996 computer control system at the Watts Bar I plant. This illustrates the need to transition and upgrade current nuclear power plant ICHMI technologies.« less

Structural design principles for delivery of bioactive components in nutraceuticals and functional foods.

PubMed

McClements, David Julian; Decker, Eric Andrew; Park, Yeonhwa; Weiss, Jochen

2009-06-01

There have been major advances in the design and fabrication of structured delivery systems for the encapsulation of nutraceutical and functional food components. A wide variety of delivery systems is now available, each with its own advantages and disadvantages for particular applications. This review begins by discussing some of the major nutraceutical and functional food components that need to be delivered and highlights the main limitations to their current utilization within the food industry. It then discusses the principles underpinning the rational design of structured delivery systems: the structural characteristics of the building blocks; the nature of the forces holding these building blocks together; and, the different ways of assembling these building blocks into structured delivery systems. Finally, we review the major types of structured delivery systems that are currently available to food scientists: lipid-based (simple, multiple, multilayer, and solid lipid particle emulsions); surfactant-based (simple micelles, mixed micelles, vesicles, and microemulsions) and biopolymer-based (soluble complexes, coacervates, hydrogel droplets, and particles). For each type of delivery system we describe its preparation, properties, advantages, and limitations.

Appraisal of the Effectiveness of CODE; The Coordinated Delivery System for the South Central Research Library Council, January to December 1970.

ERIC Educational Resources Information Center

Faibisoff, Sylvia G.

A major concern of the South Central Research Library Council in establishing an interlibrary loan network was the development of a Coordinated Delivery system (CODE). Several means of delivery were considered--the U.S. mails, commercial trucking (Greyhound, United Parcel Service), and use of the public library system's delivery services. A…

Smart linkers in polymer-drug conjugates for tumor-targeted delivery.

PubMed

Chang, Minglu; Zhang, Fang; Wei, Ting; Zuo, Tiantian; Guan, Yuanyuan; Lin, Guimei; Shao, Wei

2016-01-01

To achieve effective chemotherapy, many types of drug delivery systems have been developed for the specific environments in tumor tissues. Polymer-drug conjugates are increasingly used in tumor therapy due to several significant advantages over traditional delivery systems. In the fabrication of polymer-drug conjugates, a smart linker is an important component that joins two fragments or molecules together and can be cleared by a specific stimulus, which results in targeted drug delivery and controlled release. By regulating the conjugation between the drug and the nanocarriers, stimulus-sensitive systems based on smart linkers can offer high payloads, certified stability, controlled release and targeted delivery. In this review, we summarize the current state of smart linkers (e.g. disulfide, hydrazone, peptide, azo) used recently in various polymer-drug conjugate-based delivery systems with a primary focus on their sophisticated design principles and drug delivery mechanisms as well as in vivo processes.

Convection-Enhanced Delivery for the Treatment of Pediatric Neurologic Disorders

PubMed Central

Song, Debbie K.; Lonser, Russell R.

2013-01-01

Direct perfusion of specific regions of the central nervous system by convection-enhanced delivery is becoming more widely used for the delivery of compounds in the research and treatment of various neural disorders. In contrast to other currently available central nervous system delivery techniques, convection-enhanced delivery relies on bulk flow for distribution of solute. This allows for safe, targeted, reliable, and homogeneous delivery of small- and large-molecular-weight substances over clinically relevant volumes in a manner that bypasses the blood-central nervous system barrier. Recent studies have also shown that coinfused imaging surrogate tracers can be used to monitor and control the convective distribution of therapeutic agents in vivo. The unique features of convection-enhanced delivery, including the ability to monitor distribution in real-time, provide an opportunity to develop new research and treatment paradigms for pediatric patients with a variety of intrinsic central nervous system disorders. PMID:18952590

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

An Overview of Clinical and Commercial Impact of Drug Delivery Systems

PubMed Central

Anselmo, Aaron C.; Mitragotri, Samir

2014-01-01

Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. PMID:24747160

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

Dimensions of antenatal care service and the alacrity of mothers towards institutional delivery in South and South East Asia.

PubMed

Dixit, Priyanka; Khan, Junaid; Dwivedi, Laxmi Kant; Gupta, Amrita

2017-01-01

A number of studies have assessed the effectiveness of antenatal care (ANC) on uptake of institutional delivery care. However, none address the issue of association between the different components of ANC i.e. ANC component which is independent of health care delivery systems (timing and number of ANC visits), ANC components which depends on health care delivery systems (specific ANC procedures that women receive) with institutional delivery. Data for the study has been taken from the DHS conducted in the six selected South and South-East Asian countries during 1998-2013. The two dimensions of ANC are the key predictors. The outcome variable is a binary variable, where zero '0' denotes a home delivery and one '1' denotes an institutional delivery. In addition to probit estimation biprobit estimation method has been used to correct for the possible endogeneity. Analysis suggests that both the factors show a positive effect on institutional delivery but the level of associations are different. Probit estimation for each country suggests that the association is higher for the factor- which depends on health care delivery systems than the other factor. After correction of endogeneity through biprobit estimation we get the true associations for both the dimensions and it confirms that the ANC components which depends on health care delivery systems is more associated with the utilization of institutional delivery than the other factor. The content of care may fulfill the women's need and expectations while visiting for ANC care. The study suggests that the quality of antenatal care must be improved which depends on health care delivery systems to motivates the women to utilize the institutional delivery.

Dimensions of antenatal care service and the alacrity of mothers towards institutional delivery in South and South East Asia

PubMed Central

Dixit, Priyanka; Khan, Junaid; Dwivedi, Laxmi Kant; Gupta, Amrita

2017-01-01

Background A number of studies have assessed the effectiveness of antenatal care (ANC) on uptake of institutional delivery care. However, none address the issue of association between the different components of ANC i.e. ANC component which is independent of health care delivery systems (timing and number of ANC visits), ANC components which depends on health care delivery systems (specific ANC procedures that women receive) with institutional delivery. Methods Data for the study has been taken from the DHS conducted in the six selected South and South-East Asian countries during 1998–2013. The two dimensions of ANC are the key predictors. The outcome variable is a binary variable, where zero '0' denotes a home delivery and one '1' denotes an institutional delivery. In addition to probit estimation biprobit estimation method has been used to correct for the possible endogeneity. Findings Analysis suggests that both the factors show a positive effect on institutional delivery but the level of associations are different. Probit estimation for each country suggests that the association is higher for the factor- which depends on health care delivery systems than the other factor. After correction of endogeneity through biprobit estimation we get the true associations for both the dimensions and it confirms that the ANC components which depends on health care delivery systems is more associated with the utilization of institutional delivery than the other factor. Conclusions The content of care may fulfill the women’s need and expectations while visiting for ANC care. The study suggests that the quality of antenatal care must be improved which depends on health care delivery systems to motivates the women to utilize the institutional delivery. PMID:28742809

Understanding the organization of public health delivery systems: an empirical typology.

PubMed

Mays, Glen P; Scutchfield, F Douglas; Bhandari, Michelyn W; Smith, Sharla A

2010-03-01

Policy discussions about improving the U.S. health care system increasingly recognize the need to strengthen its capacities for delivering public health services. A better understanding of how public health delivery systems are organized across the United States is critical to improvement. To facilitate the development of such evidence, this article presents an empirical method of classifying and comparing public health delivery systems based on key elements of their organizational structure. This analysis uses data collected through a national longitudinal survey of local public health agencies serving communities with at least 100,000 residents. The survey measured the availability of twenty core public health activities in local communities and the types of organizations contributing to each activity. Cluster analysis differentiated local delivery systems based on the scope of activities delivered, the range of organizations contributing, and the distribution of effort within the system. Public health delivery systems varied widely in organizational structure, but the observed patterns of variation suggested that systems adhere to one of seven distinct configurations. Systems frequently migrated from one configuration to another over time, with an overall trend toward offering a broader scope of services and engaging a wider range of organizations. Public health delivery systems exhibit important structural differences that may influence their operations and outcomes. The typology developed through this analysis can facilitate comparative studies to identify which delivery system configurations perform best in which contexts.

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

2016-07-30

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.

Co-delivery of vascular endothelial growth factor and angiopoietin-1 using injectable microsphere/hydrogel hybrid systems for therapeutic angiogenesis.

PubMed

Shin, Seung-Hwa; Lee, Jangwook; Ahn, Dong-Gyun; Lee, Kuen Yong

2013-08-01

We hypothesized that combined delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) using microsphere/hydrogel hybrid systems could enhance mature vessel formation compared with administration of each factor alone. Hybrid delivery systems composed of alginate hydrogels and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres containing angiogenic factors were prepared. The release behavior of angiogenic factors from hybrid systems was monitored in vitro. The hybrid systems were injected into an ischemic rodent model, and blood vessel formation at the ischemic site was evaluated. The sustained release over 4 weeks of both VEGF and Ang-1 from hybrid systems was achieved in vitro. Co-delivery of VEGF and Ang-1 was advantageous to retain muscle tissues and significantly induced vessel enlargement at the ischemic site, compared to mice treated with either VEGF or Ang-1 alone. Sustained and combined delivery of VEGF and Ang-1 significantly enhances vessel enlargement at the ischemic site, compared with sustained delivery of either factor alone. Microsphere/hydrogel hybrid systems may be a promising vehicle for delivery of multiple drugs for many therapeutic applications.