Elastin-Like Recombinamers As Smart Drug Delivery Systems.

PubMed

Arias, F Javier; Santos, Mercedes; Ibanez-Fonseca, Arturo; Pina, Maria Jesus; Serrano, Sofía

2018-02-19

Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

MDOT implementation plan for global positioning systems (GPS) technology in planning, design, and construction delivery.

DOT National Transportation Integrated Search

2010-09-13

Global Positioning System (GPS) technology offers advantages to transportation agencies in the planning, design and construction stages of project delivery. This research study will develop a guide for Mississippi Department of Transportation (MDOT) ...

Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.

PubMed

Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça

2017-05-01

In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.

Connecting drug delivery reality to smart materials design.

PubMed

Grainger, David W

2013-09-15

Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

Subsystem Testing and Flight Test Instrumentation.

DTIC Science & Technology

1981-04-01

systems has made the job of the tester increasingly difficult. These systems are being " , designed to accomplish the entire spectrum of tasks from pure...52 destinations, targets, and avoidance areas. The software program also allows the aircrew to designate two weapon delivery programs from the...The basic design dW objective of the system is to provide an increased capability for weapons delivery against preplanned targets when operating at high

Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

ERIC Educational Resources Information Center

Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

2010-01-01

A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

Introduction for Design of Nanoparticle Based Drug Delivery Systems.

PubMed

Edgar, Jun Yan Chan; Wang, Hui

2017-01-01

Conventional drug delivery systems contain numerous limitations such as limited targeting, low therapeutic indices, poor water solubility, and the induction of drug resistances. In order to overcome the drawbacks of conventional pathway of drug delivery, nanoparticle delivery systems are therefore designed and used as the drug carriers. Nanoparticle based drug delivery systems have been rapidly growing and are being applied to various sections of biomedicine. Drug nanocarriers based on dendrimers, liposomes, self-assembling peptides, watersoluble polymers, and block copolymer micelles are the most extensively studied types of drug delivery systems and some of them are being used in clinical therapy. In particular for cancer therapy, antineoplastic drugs are taking advantage of nanoparticulate drug carriers to improve the cure efficacy. Nanoparticle based drug carriers are capable of improving the therapeutic effectiveness of the drugs by using active targeting for the site-specific delivery, passive targeting mechanisms such as enhanced permeability and retention (EPR), de novo synthesis and uptake of low density liposome in cancer cells or by being water-soluble to improve the suboptimal pharmacokinetics in limited water-soluble delivery methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development and Application of a Systems Engineering Framework to Support Online Course Design and Delivery

ERIC Educational Resources Information Center

Bozkurt, Ipek; Helm, James

2013-01-01

This paper develops a systems engineering-based framework to assist in the design of an online engineering course. Specifically, the purpose of the framework is to provide a structured methodology for the design, development and delivery of a fully online course, either brand new or modified from an existing face-to-face course. The main strength…

Teledermatology in a capitated delivery system using distributed information architecture: design and development.

PubMed

Kvedar, J C; Menn, E R; Baradagunta, S; Smulders-Meyer, O; Gonzalez, E

1999-01-01

This report describes the design, development, and technical evaluation of a teledermatology system utilizing digital images and electronic forms captured through, stored on, and viewed through a common web server in an urban capitated delivery system. The authors designed a system whereby a primary care physician was able to seek a dermatologic consultation electronically, provide the specialist with digital images acquired according to a standardized protocol, and review the specialist response within 2 business days of the request. The settings were two primary care practices in eastern Massachusetts that were affiliated with a large integrated delivery system. Technical evaluation of the effectiveness of the system involved 18 patients. Main outcome measures included physician and patient satisfaction and comfort and efficiency of care delivery. In 15 cases, the consultant dermatologist was comfortable in providing definitive diagnosis and treatment recommendations. In 3 cases, additional information (laboratory studies or more history) was requested. There were no instances where the dermatologist felt that a face-to-face visit was necessary. This novel approach shows promise for the delivery of specialist expertise via the internet. Cost-effectiveness studies may be necessary for more widespread implementation.

Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

PubMed Central

Shelate, Pragna; Dave, Divyang

2016-01-01

The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

Endoscopic ultrasound-guided biliary drainage using a newly designed metal stent with a thin delivery system: a preclinical study in phantom and porcine models.

PubMed

Minaga, Kosuke; Kitano, Masayuki; Itonaga, Masahiro; Imai, Hajime; Miyata, Takeshi; Yamao, Kentaro; Tamura, Takashi; Nuta, Junya; Warigaya, Kenji; Kudo, Masatoshi

2017-12-08

This study was designed to evaluate the feasibility and safety of a newly designed self-expandable metal stent for endoscopic ultrasound-guided biliary drainage (EUS-BD) when it was delivered via three different stent delivery systems: a 7.5Fr delivery catheter with a bullet-shaped tip (7.5Fr-bullet), a 7Fr catheter with a bullet-shaped tip (7Fr-bullet), or a 7Fr catheter with a tee-shaped tip (7Fr-tee). This experimental study utilized a porcine model of biliary dilatation involving ten pigs. In the animal study, technical feasibility and clinical outcomes of the stent when placed with each of the delivery systems were examined. In addition, a phantom model was used to measure the resistance of these delivery systems to advancement. Phantom experiments showed that, compared with 7Fr-bullet, 7Fr-tee had less resistance force to the advancement of the stent delivery system. EUS-BD was technically successful in all ten pigs. Fistulous tract dilation was necessary in 100% (2/2), 75% (3/4), and 0% (0/4) of the pigs that underwent EUS-BD using 7.5Fr-bullet, 7Fr-bullet, and 7Fr-tee, respectively. There were no procedure-related complications. Our newly designed metal stent may be feasible and safe for EUS-BD, particularly when delivered by 7Fr-tee, because it eliminates the need for fistulous tract dilation.

Intravital Microscopy Imaging Approaches for Image-Guided Drug Delivery Systems

PubMed Central

Kirui, Dickson K.; Ferrari, Mauro

2016-01-01

Rapid technical advances in the field of non-linear microscopy have made intravital microscopy a vital pre-clinical tool for research and development of imaging-guided drug delivery systems. The ability to dynamically monitor the fate of macromolecules in live animals provides invaluable information regarding properties of drug carriers (size, charge, and surface coating), physiological, and pathological processes that exist between point-of-injection and the projected of site of delivery, all of which influence delivery and effectiveness of drug delivery systems. In this Review, we highlight how integrating intravital microscopy imaging with experimental designs (in vitro analyses and mathematical modeling) can provide unique information critical in the design of novel disease-relevant drug delivery platforms with improved diagnostic and therapeutic indexes. The Review will provide the reader an overview of the various applications for which intravital microscopy has been used to monitor the delivery of diagnostic and therapeutic agents and discuss some of their potential clinical applications. PMID:25901526

Recent advances in ophthalmic drug delivery

PubMed Central

Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

2011-01-01

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

Design of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription

NASA Astrophysics Data System (ADS)

Jang, Mihue; Kim, Jong Hwan; Nam, Hae Yun; Kwon, Ick Chan; Ahn, Hyung Jun

2015-08-01

For therapeutic applications of siRNA, there are technical challenges with respect to targeted and systemic delivery. We here report a new siRNA carrier, RNAtr NPs, in a way that multiple tandem copies of RNA hairpins as a result of rolling circle transcription (RCT) can be readily adapted in tumour-targeted and systemic siRNA delivery. RNAtr NPs provide a means of condensing large amounts of multimeric RNA transcripts into the compact nanoparticles, especially without the aid of polycationic agents, and thus reduce the risk of immunogenicity and cytotoxicity by avoiding the use of synthetic polycationic reagents. This strategy allows the design of a platform technology for systemic delivery of siRNA to tumour sites, because RCT reaction, which enzymatically generates RNA polymers in multiple copy numbers at low cost, can lead to directly accessible routes to targeted and systemic delivery. Therefore, RNAtr NPs suggest great potentials as the siRNA therapeutics for cancer treatment.

Modeling hospital surgical delivery process design using system simulation: optimizing patient flow and bed capacity as an illustration.

PubMed

Kumar, Sameer

2011-01-01

It is increasingly recognized that hospital operation is an intricate system with limited resources and many interacting sources of both positive and negative feedback. The purpose of this study is to design a surgical delivery process in a county hospital in the U.S where patient flow through a surgical ward is optimized. The system simulation modeling is used to address questions of capacity planning, throughput management and interacting resources which constitute the constantly changing complexity that characterizes designing a contemporary surgical delivery process in a hospital. The steps in building a system simulation model is demonstrated using an example of building a county hospital in a small city in the US. It is used to illustrate a modular system simulation modeling of patient surgery process flows. The system simulation model development will enable planners and designers how they can build in overall efficiencies in a healthcare facility through optimal bed capacity for peak patient flow of emergency and routine patients.

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

DTIC Science & Technology

1982-06-29

DESIGN, CONSTRUCTION, DEMONSTRATION AND DELIVERY OF WE DA4I &NARROW GAP CONTRACT NO. NOOGOO-81-C-E923 TO DAVID TAYLOR NAVAL RESEARCH AND DEVELOPMENT...the automated * Narrow Gap welding process, is the narrow (3/8 - inch), square-butt joint *design. This narrow joint greatly reduces the volume of weld...AD-i45 495 DESIGN CONSTRUCTION DEMONSTRATION AiND DELIVERY OF RN 1/j AUrOMATED NARROW GAP WELDING SYSTEMI() CRC AUTOMATIC WELDING CO HOUSTON TX 29

Microfabrication for Drug Delivery

PubMed Central

Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

2016-01-01

This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

MDOT implementation plan for GPS technology in planning, design, and construction delivery

DOT National Transportation Integrated Search

2010-09-13

Global Positioning System (GPS) technology offers advantages to transportation agencies in the planning, design and construction stages of project delivery. This research study will develop a guide for Mississippi Department of Transportation (MDOT) ...

Integration of Biosensors and Drug Delivery Technologies for Early Detection and Chronic Management of Illness

PubMed Central

Ngoepe, Mpho; Choonara, Yahya E.; Tyagi, Charu; Tomar, Lomas Kumar; du Toit, Lisa C.; Kumar, Pradeep; Ndesendo, Valence M. K.; Pillay, Viness

2013-01-01

Recent advances in biosensor design and sensing efficacy need to be amalgamated with research in responsive drug delivery systems for building superior health or illness regimes and ensuring good patient compliance. A variety of illnesses require continuous monitoring in order to have efficient illness intervention. Physicochemical changes in the body can signify the occurrence of an illness before it manifests. Even with the usage of sensors that allow diagnosis and prognosis of the illness, medical intervention still has its downfalls. Late detection of illness can reduce the efficacy of therapeutics. Furthermore, the conventional modes of treatment can cause side-effects such as tissue damage (chemotherapy and rhabdomyolysis) and induce other forms of illness (hepatotoxicity). The use of drug delivery systems enables the lowering of side-effects with subsequent improvement in patient compliance. Chronic illnesses require continuous monitoring and medical intervention for efficient treatment to be achieved. Therefore, designing a responsive system that will reciprocate to the physicochemical changes may offer superior therapeutic activity. In this respect, integration of biosensors and drug delivery is a proficient approach and requires designing an implantable system that has a closed loop system. This offers regulation of the changes by means of releasing a therapeutic agent whenever illness biomarkers prevail. Proper selection of biomarkers is vital as this is key for diagnosis and a stimulation factor for responsive drug delivery. By detecting an illness before it manifests by means of biomarkers levels, therapeutic dosing would relate to the severity of such changes. In this review various biosensors and drug delivery systems are discussed in order to assess the challenges and future perspectives of integrating biosensors and drug delivery systems for detection and management of chronic illness. PMID:23771157

Promoting Quality of Program Delivery via an Internet Message Delivery System

ERIC Educational Resources Information Center

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

2013-01-01

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

Pharmacoinformatic approaches to understand complexation of dendrimeric nanoparticles with drugs

NASA Astrophysics Data System (ADS)

Jain, Vaibhav; Bharatam, Prasad V.

2014-02-01

Nanoparticle based drug delivery systems are gaining popularity due to their wide spectrum advantages over traditional drug delivery systems; among them, dendrimeric nano-vectors are the most widely explored carriers for pharmaceutical and biomedical applications. The precise mechanism of encapsulation of drug molecules inside the dendritic matrix, delivery of drugs into specific cells, interactions of nano-formulation with biological targets and proteins, etc. present a substantial challenge to the scientific understanding of the subject. Computational methods complement experimental techniques in the design and optimization of drug delivery systems, thus minimizing the investment in drug design and development. Significant progress in computer simulations could facilitate an understanding of the precise mechanism of encapsulation of bioactive molecules and their delivery. This review summarizes the pharmacoinformatic studies spanning from quantum chemical calculations to coarse-grained simulations, aimed at providing better insight into dendrimer-drug interactions and the physicochemical parameters influencing the binding and release mechanism of drugs.

PubMed on Tap: discovering design principles for online information delivery to handheld computers.

PubMed

Hauser, Susan E; Demner-Fushman, Dina; Ford, Glenn; Thoma, George R

2004-01-01

Online access to biomedical information from handheld computers will be a valuable adjunct to other popular medical applications if information delivery systems are designed with handheld computers in mind. The goal of this project is to discover design principles to facilitate practitioners' access to online medical information at the point-of-care. A prototype system was developed to serve as a testbed for this research. Using the testbed, an initial evaluation has yielded several user interface design principles. Continued research is expected to discover additional user interface design principles as well as guidelines for results organization and system performance

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

A system for EPID-based real-time treatment delivery verification during dynamic IMRT treatment.

PubMed

Fuangrod, Todsaporn; Woodruff, Henry C; van Uytven, Eric; McCurdy, Boyd M C; Kuncic, Zdenka; O'Connor, Daryl J; Greer, Peter B

2013-09-01

To design and develop a real-time electronic portal imaging device (EPID)-based delivery verification system for dynamic intensity modulated radiation therapy (IMRT) which enables detection of gross treatment delivery errors before delivery of substantial radiation to the patient. The system utilizes a comprehensive physics-based model to generate a series of predicted transit EPID image frames as a reference dataset and compares these to measured EPID frames acquired during treatment. The two datasets are using MLC aperture comparison and cumulative signal checking techniques. The system operation in real-time was simulated offline using previously acquired images for 19 IMRT patient deliveries with both frame-by-frame comparison and cumulative frame comparison. Simulated error case studies were used to demonstrate the system sensitivity and performance. The accuracy of the synchronization method was shown to agree within two control points which corresponds to approximately ∼1% of the total MU to be delivered for dynamic IMRT. The system achieved mean real-time gamma results for frame-by-frame analysis of 86.6% and 89.0% for 3%, 3 mm and 4%, 4 mm criteria, respectively, and 97.9% and 98.6% for cumulative gamma analysis. The system can detect a 10% MU error using 3%, 3 mm criteria within approximately 10 s. The EPID-based real-time delivery verification system successfully detected simulated gross errors introduced into patient plan deliveries in near real-time (within 0.1 s). A real-time radiation delivery verification system for dynamic IMRT has been demonstrated that is designed to prevent major mistreatments in modern radiation therapy.

Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

NASA Astrophysics Data System (ADS)

Dawidczyk, Charlene; Russell, Luisa; Searson, Peter

2014-08-01

The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics and tumor accumulation. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.

PubMed

Hua, Susan; Marks, Ellen; Schneider, Jennifer J; Keely, Simon

2015-07-01

Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Drug delivery across length scales.

PubMed

Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

2018-02-20

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

Pulsed Dose Delivery of Oxygen in Mechanically Ventilated Pigs with Acute Lung Injury

DTIC Science & Technology

2013-03-01

collapse or arrhythmia were encountered after administration of oleic acid, chest compressions, electrical defibrillation , and epinephrine (0.1-1 mg/kg...endotracheal tube to continuously measure the oxygen content of the gas in the circuit. We designed the study as a crossover trial, so each animal served as... designed to prove that a pulsed dose delivery system would be a better method of oxygen delivery, it is interesting to note that pulsed dose delivery did

From conventional towards new - natural surfactants in drug delivery systems design: current status and perspectives.

PubMed

Savić, Snezana; Tamburić, Slobodanka; Savić, Miroslav M

2010-03-01

Surfactants play an important role in the development of both conventional and advanced (colloidal) drug delivery systems. There are several commercial surfactants, but a proportionally small group of them is approved as pharmaceutical excipients, recognized in various pharmacopoeias and therefore widely accepted by the pharmaceutical industry. The review covers some of the main categories of natural, sugar-based surfactants (alkyl polyglucosides and sugar esters) as prospective pharmaceutical excipients. It provides analysis of the physicochemical characteristics of sugar-based surfactants and their possible roles in the design of conventional or advanced drug delivery systems for different routes of administration. Summary and analysis of recent data on functionality, applied concentrations and formulation improvements produced by alkyl polyglucosides and sugar esters in different conventional and advanced delivery systems could be of interest to researchers dealing with drug formulation. Recent FDA certification of an alkyl polyglucoside surfactant for topical formulation presents a significant step in the process of recognition of this relatively new group of surfactants. This could trigger further research into the potential benefits of naturally derived materials in both conventional and new drug delivery systems.

Extracellular control of intracellular drug release for enhanced safety of anti-cancer chemotherapy

NASA Astrophysics Data System (ADS)

Zhu, Qian; Qi, Haixia; Long, Ziyan; Liu, Shang; Huang, Zhen; Zhang, Junfeng; Wang, Chunming; Dong, Lei

2016-06-01

The difficulty of controlling drug release at an intracellular level remains a key challenge for maximising drug safety and efficacy. We demonstrate herein a new, efficient and convenient approach to extracellularly control the intracellular release of doxorubicin (DOX), by designing a delivery system that harnesses the interactions between the system and a particular set of cellular machinery. By simply adding a small-molecule chemical into the cell medium, we could lower the release rate of DOX in the cytosol, and thereby increase its accumulation in the nuclei while decreasing its presence at mitochondria. Delivery of DOX with this system effectively prevented DOX-induced mitochondria damage that is the main mechanism of its toxicity, while exerting the maximum efficacy of this anti-cancer chemotherapeutic agent. The present study sheds light on the design of drug delivery systems for extracellular control of intracellular drug delivery, with immediate therapeutic implications.

Cell-Based Biohybrid Drug Delivery Systems: The Best of the Synthetic and Natural Worlds.

PubMed

Banskota, Samagya; Yousefpour, Parisa; Chilkoti, Ashutosh

2017-01-01

The goal of drug delivery is to deliver therapeutics to the site of disease while reducing unwanted side effects. In recent years, a diverse variety of synthetic nano and microparticles have been developed as drug delivery systems. The success of these systems for drug delivery lies in their ability to overcome biological barriers such as the blood-brain barrier, to evade immune clearance and avoid nonspecific biodistribution. This Review provides an overview of recent advances in the design of biohybrid drug delivery systems, which combine cells with synthetic systems to overcome some of these biological hurdles. Examples include eukaryotic cells, such as stem cells, red blood cells, immune cells, platelets, and cancer cells that are used to carry drug-loaded synthetic particles. Synthetic particles can also be cloaked with naturally derived cell membranes and thereby evade immune clearance, exhibit prolonged systemic circulation, and target specific tissues by capitalizing on the interaction/homing tendency of certain cells and their membrane components to particular tissues. Different designs of cell-based biohybrid systems and their applications, as well as their promise and limitations, are discussed herein. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Advances of tumor targeting peptides drug delivery system with pH-sensitive activities].

PubMed

Ma, Yin-yun; Li, Li; Huang, Hai-feng; Gou, San-hu; Ni, Jing-man

2016-05-01

The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism,type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

Engaging Faculty in Telecommunications-Based Instructional Delivery Systems.

ERIC Educational Resources Information Center

Swalec, John J.

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

A multi-institutional dosimetry audit of rotational intensity-modulated radiotherapy.

PubMed

Clark, Catharine H; Hussein, Mohammad; Tsang, Yatman; Thomas, Russell; Wilkinson, Dean; Bass, Graham; Snaith, Julia; Gouldstone, Clare; Bolton, Steve; Nutbrown, Rebecca; Venables, Karen; Nisbet, Andrew

2014-11-01

Rotational IMRT (VMAT and Tomotherapy) has now been implemented in many radiotherapy centres. An audit to verify treatment planning system modelling and treatment delivery has been undertaken to ensure accurate clinical implementation. 34 institutions with 43 treatment delivery systems took part in the audit. A virtual phantom planning exercise (3DTPS test) and a clinical trial planning exercise were planned and independently measured in each institution using a phantom and array combination. Point dose differences and global gamma index (γ) were calculated in regions corresponding to PTVs and OARs. Point dose differences gave a mean (±sd) of 0.1±2.6% and 0.2±2.0% for the 3DTPS test and clinical trial plans, respectively. 34/43 planning and delivery combinations achieved all measured planes with >95% pixels passing γ<1 at 3%/3mm and rose to 42/43 for clinical trial plans. A statistically significant difference in γ pass rates (p<0.01) was seen between planning systems where rotational IMRT modelling had been designed for the manufacturer's own treatment delivery system and those designed independently of rotational IMRT delivery. A dosimetry audit of rotational radiotherapy has shown that TPS modelling and delivery for rotational IMRT can achieve high accuracy of plan delivery. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Adaptive Aerosol Delivery (AAD) technology: Past, present, and future.

PubMed

Denyer, John; Dyche, Tony

2010-04-01

Conventional aerosol delivery systems and the availability of new technologies have led to the development of "intelligent" nebulizers such as the I-neb Adaptive Aerosol Delivery (AAD) System. Based on the AAD technology, the I-neb AAD System has been designed to continuously adapt to changes in the patient's breathing pattern, and to pulse aerosol only during the inspiratory part of the breathing cycle. This eliminates waste of aerosol during exhalation, and creates a foundation for precise aerosol (dose) delivery. To facilitate the delivery of precise metered doses of aerosol to the patient, a unique metering chamber design has been developed. Through the vibrating mesh technology, the metering chamber design, and the AAD Disc function, the aerosol output rate and metered (delivered) dose can be tailored to the demands of the specific drug to be delivered. In the I-neb AAD System, aerosol delivery is guided through two algorithms, one for the Tidal Breathing Mode (TBM), and one for slow and deep inhalations, the Target Inhalation Mode (TIM). The aim of TIM is to reduce the treatment time by increasing the total inhalation time per minute, and to increase lung deposition by reducing impaction in the upper airways through slow and deep inhalations. A key feature of the AAD technology is the patient feedback mechanisms that are provided to guide the patient on delivery performance. These feedback signals, which include visual, audible, and tactile forms, are configured in a feedback cascade that leads to a high level of compliance with the use of the I-neb AAD System. The I-neb Insight and the Patient Logging System facilitate a further degree of sophistication to the feedback mechanisms, by providing information on long term adherence and compliance data. These can be assessed by patients and clinicians via a Web-based delivery of information in the form of customized graphical analyses.

Liposome-chaperoned cell-free synthesis for the design of proteoliposomes: Implications for therapeutic delivery.

PubMed

Lu, Mei; Zhao, Xiaoyun; Xing, Haonan; Xun, Zhe; Yang, Tianzhi; Cai, Cuifang; Wang, Dongkai; Ding, Pingtian

2018-04-03

Cell-free (CF) protein synthesis has emerged as a powerful technique platform for efficient protein production in vitro. Liposomes have been widely studied as therapeutic carriers due to their biocompatibility, biodegradability, low toxicity, flexible surface manipulation, easy preparation, and higher cargo encapsulation capability. However, rapid immune clearance, insufficient targeting capacity, and poor cytoplasmic delivery efficiency substantially restrict their clinical application. The incorporation of functional membrane proteins (MPs) or peptides allows the transfer of biological properties to liposomes and imparts them with improved circulation, increased targeting, and efficient intracellular delivery. Liposome-chaperoned CF synthesis enables production of proteoliposomes in one-step reaction, which not only substantially simplifies the production procedure but also keeps protein functionality intact. Building off these observations, proteoliposomes with integrated MPs represent an excellent candidate for therapeutic delivery. In this review, we describe recent advances in CF synthesis with emphasis on detailing key factors for improving CF expression efficiency. Furthermore, we provide insights into strategies for rational design of proteoliposomal nanodelivery systems via CF synthesis. Liposome-chaperoned CF synthesis has emerged as a powerful approach for the design of recombinant proteoliposomes in one-step reaction. The incorporation of bioactive MPs or peptides into liposomes via CF synthesis can facilitate the development of proteoliposomal nanodelivery systems with improved circulation, increased targeting, and enhanced cellular delivery capacity. Moreover, by adapting lessons learned from natural delivery vehicles, novel bio-inspired proteoliposomes with enhanced delivery properties could be produced in CF systems. In this review, we first give an overview of CF synthesis with focus on enhancing protein expression in liposome-chaperoned CF systems. Furthermore, we intend to provide insight into harnessing CF-synthesized proteoliposomes for efficient therapeutic delivery. Copyright © 2018. Published by Elsevier Ltd.

Self-assembling nucleic acid delivery vehicles via linear, water-soluble, cyclodextrin-containing polymers.

PubMed

Davis, M E; Pun, S H; Bellocq, N C; Reineke, T M; Popielarski, S R; Mishra, S; Heidel, J D

2004-01-01

Non-viral (synthetic) nucleic acid delivery systems have the potential to provide for the practical application of nucleic acid-based therapeutics. We have designed and prepared a tunable, non-viral nucleic acid delivery system that self-assembles with nucleic acids and centers around a new class of polymeric materials; namely, linear, water-soluble cyclodextrin-containing polymers. The relationships between polymer structure and gene delivery are illustrated, and the roles of the cyclodextrin moieties for minimizing toxicity and forming inclusion complexes in the self-assembly processes are highlighted. This vehicle is the first example of a polymer-based gene delivery system formed entirely by self-assembly.

Colon-targeted oral drug delivery systems: design trends and approaches.

PubMed

Amidon, Seth; Brown, Jack E; Dave, Vivek S

2015-08-01

Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Advancement of multifunctional hybrid nanogel systems: Construction and application in drug co-delivery and imaging technique.

PubMed

Ma, Yakun; Ge, Yanxiu; Li, Lingbing

2017-02-01

Nanogel-based multifunctional drug delivery systems, especially hybrid nanogels and multicompartment nanogels have drawn more and more extensive attention from the researchers in pharmacy because it can result in achieving a superior functionality through the synergistic property enhancement of each component. The unique hybrid and compartmentalized structures provide the great potential for co-delivery of multiple agents even the multiple agents with different physicochemical properties. Otherwise the hybrid nanogel encapsulating optical and magnetic resonance imaging contrast can be utilized in imaging technique for disease diagnosis. More importantly through nanogel-based multifunctional drug delivery systems the stimuli-responsive features might be easily employed for the design of targeted release of drug. This review summarizes the construction of diverse hybrid nanogels and multicompartment nanogels. The application in co-delivery of multiple agents and imaging agents for diagnosis as well as the application in the design of stimuli-responsive multifunctional nanogels as drug delivery are also reviewed and discussed. The future prospects in application of multifunctional nanogels will be also discussed in this review. Copyright © 2016 Elsevier B.V. All rights reserved.

Modular reservoir concept for MEMS-based transdermal drug delivery systems

NASA Astrophysics Data System (ADS)

Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.

2014-11-01

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.

PubMed

Zhang, Rui Xue; Li, Jason; Zhang, Tian; Amini, Mohammad A; He, Chunsheng; Lu, Brian; Ahmed, Taksim; Lip, HoYin; Rauth, Andrew M; Wu, Xiao Yu

2018-05-01

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.

Nanomaterials in cancer-therapy drug delivery system.

PubMed

Zhang, Gen; Zeng, Xin; Li, Ping

2013-05-01

Nanomaterials can enhance the delivery and treatment efficiency of anti-cancer drugs, and the mechanisms of the tumor-reducing activity of nanomaterials with cancer drug have been investigated. The task for drug to reach pathological areas has facilitated rapid advances in nanomedicine. Herein, we summarize promising findings with respect to cancer therapeutics based on nano-drug delivery vectors. Relatively high toxicity of uncoated nanoparticles restricts the use of these materials in humans. In order to reduce toxicity, many approaches have focused on the encapsulation of nanoparticles with biocompatible materials. Efficient delivery systems have been developed that utilized nanoparticles loaded with high dose of cancer drug in the presence of bilayer molecules. Well-established nanotechnologies have been designed for drug delivery with specific bonding. Surface-modified nanoparticles as vehicles for drug delivery system that contains multiple nano-components, each specially designed to achieve aimed task for the emerging application delivery of therapeutics. Drug-coated polymer nanoparticles could efficiently increase the intracellular accumulation of anti-cancer drugs. This review also introduces the nanomaterials with drug on the induction of apoptosis in cancer cells in vitro and in vivo. Direct interactions between the particles and cellular molecules to cause adverse biological responses are also discussed.

Training of Trainers: Trainer Manual.

ERIC Educational Resources Information Center

University Research Corp., Bethesda, MD.

This manual is designed to train individuals to deliver courses developed within the National Training System of the National Institute on Drug Abuse (NIDA). The training guide, describes the content and activities that constitute training delivery, identifies behaviors and skills associated with training delivery, elaborates on program design and…

Design of a Computer-Adaptive Test to Measure English Literacy and Numeracy in the Singapore Workforce: Considerations, Benefits, and Implications

ERIC Educational Resources Information Center

Jacobsen, Jared; Ackermann, Richard; Eguez, Jane; Ganguli, Debalina; Rickard, Patricia; Taylor, Linda

2011-01-01

A computer adaptive test (CAT) is a delivery methodology that serves the larger goals of the assessment system in which it is embedded. A thorough analysis of the assessment system for which a CAT is being designed is critical to ensure that the delivery platform is appropriate and addresses all relevant complexities. As such, a CAT engine must be…

Multilayered materials based on biopolymers as drug delivery systems.

PubMed

Vilela, Carla; Figueiredo, Ana R P; Silvestre, Armando J D; Freire, Carmen S R

2017-02-01

The design of efficient therapeutic delivery devices has become a tremendously active area of research with a strong contribution from the layer-by-layer (LbL) technology. The application of this simple yet firmly established technique for the design of drug reservoirs originates a multitude of multilayered systems of tailored architecture and with a high level of control of drug administration. Areas covered: This review will focus on the most recent and original research on LbL assemblies based on biopolymers including polysaccharides, polypeptides and proteins, with potential use in drug delivery. Herein, drug reservoirs consisting of multilayered planar films and capsules will be examined with emphasis on the ones benefiting from the non-cytotoxic and biocompatible nature of biopolymers, which are suitable to load, protect and release a high payload of toxic and fragile drugs. Expert opinion: The combination of biopolymers with LbL technology has undergone extensive research, still, there is a multitude of R&D opportunities for the design of smart drug delivery systems with distinct multilayered morphologies, low immunological response, non-invasive drug release devices, as well as the design of theranostic systems combining diagnostics and therapeutic features. Further developments in terms of scaling towards mass production in the pharmaceutical industry are expected in the long-term.

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

NASA Astrophysics Data System (ADS)

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

2014-01-01

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

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

DTIC Science & Technology

1983-03-31

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

The Development and Design of a Prototype Ultra High Pressure P-19 Firefighting Vehicle

DTIC Science & Technology

2007-02-03

the energizing affects of a delivery pressure 4 times (approximately 1200 psi) the magnitude of the standard system at the bumper turret nozzle...permanently extinguish a fire. The onboard CAF system is capable of 300 gpm delivery of foam at approximately 165 psi out of the bumper turret, and a...hand line flowing 45 gpm at approximately 165 psi also. The dry chemical system is designed to flow approximately 7 pps from the bumper turret, and 5

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.

Short and long term improvements in quality of chronic care delivery predict program sustainability.

PubMed

Cramm, Jane Murray; Nieboer, Anna Petra

2014-01-01

Empirical evidence on sustainability of programs that improve the quality of care delivery over time is lacking. Therefore, this study aims to identify the predictive role of short and long term improvements in quality of chronic care delivery on program sustainability. In this longitudinal study, professionals [2010 (T0): n=218, 55% response rate; 2011 (T1): n=300, 68% response rate; 2012 (T2): n=265, 63% response rate] from 22 Dutch disease-management programs completed surveys assessing quality of care and program sustainability. Our study findings indicated that quality of chronic care delivery improved significantly in the first 2 years after implementation of the disease-management programs. At T1, overall quality, self-management support, delivery system design, and integration of chronic care components, as well as health care delivery and clinical information systems and decision support, had improved. At T2, overall quality again improved significantly, as did community linkages, delivery system design, clinical information systems, decision support and integration of chronic care components, and self-management support. Multilevel regression analysis revealed that quality of chronic care delivery at T0 (p<0.001) and quality changes in the first (p<0.001) and second (p<0.01) years predicted program sustainability. In conclusion this study showed that disease-management programs based on the chronic care model improved the quality of chronic care delivery over time and that short and long term changes in the quality of chronic care delivery predicted the sustainability of the projects. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Designing Online Learning. Knowledge Series: A Topical, Start-Up Guide to Distance Education Practice and Delivery.

ERIC Educational Resources Information Center

Mishra, Sanjaya

The term "online learning" refers to an Internet- or intranet-based teaching and learning system designed for World Wide Web-based delivery without face-to-face contact between teacher and learner. The Internet is the backbone of online learning. The following media are available to designers of online courses: text; graphics and images;…

Advanced engineering design program at the University of Illinois for the 1987-1988 academic year

NASA Technical Reports Server (NTRS)

Sivier, Kenneth R.; Lembeck, Michael F.

1988-01-01

The participation of the University of Illinois at Urbana-Champaign in the NASA/USRA Universities Advanced Engineering Design Program (Space) is reviewed for the 1987 to 88 academic year. The University's design project was the Manned Marsplane and Delivery System. In the spring of 1988 semester, 107 students were enrolled in the Aeronautical and Astronautical Engineering Departments' undergraduate Aerospace Vehicle Design course. These students were divided into an aircraft section (responsible for the Marsplane design), and a spacecraft section (responsible for the Delivery System Design). The design results are presented in Final Design Reports, copies of which are attached. In addition, five students presented a summary of the design results at the Program's Summer Conference.

Silk-based delivery systems of bioactive molecules

PubMed Central

Numata, Keiji; Kaplan, David L

2010-01-01

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

Web Page Design in Distance Education

ERIC Educational Resources Information Center

Isman, Aytekin; Dabaj, Fahme; Gumus, Agah; Altinay, Fahriye; Altinay, Zehra

2004-01-01

Distance education is contemporary process of the education. It facilitates fast, easy delivery of information with its concrete hardware and software tools. The development of high technology, internet and web-design delivering become impact of effective using as delivery system to the students. Within the global perspective, even the all work…

Web Page Design in Distance Education

ERIC Educational Resources Information Center

Isman, Aytekin; Dabaj, Fahme; Gumus, Agah; Altinay, Fahriye; Altinay, Zehra

2004-01-01

Distance education is contemporary process of the education. It facilitates fast, easy delivery of information with its concrete hardware and software tools. The development of high technology, Internet and web-design delivering become impact of effective using as delivery system to the students. Within the global perspective, even the all work…

Microprocessor Based Temperature Control of Liquid Delivery with Flow Disturbances.

ERIC Educational Resources Information Center

Kaya, Azmi

1982-01-01

Discusses analytical design and experimental verification of a PID control value for a temperature controlled liquid delivery system, demonstrating that the analytical design techniques can be experimentally verified by using digital controls as a tool. Digital control instrumentation and implementation are also demonstrated and documented for…

Noncovalent interaction-assisted drug delivery system with highly efficient uptake and release of paclitaxel for anticancer therapy.

PubMed

Wei, Yuping; Ma, Liang; Zhang, Liang; Xu, Xia

2017-01-01

An effective drug delivery system requires efficient drug uptake and release inside cancer cells. Here, we report a novel drug delivery system, in which paclitaxel (PTX) interacts with a novel cell penetrating peptide (CPP) through noncovalent interaction designed based on molecular simulations. This CPP/PTX complex confers high efficiency in delivering PTX into cancer cells not by endocytosis but by an energy-independent pathway. Once inside cells, the noncovalent interaction between PTX and the CPP may allow fast release of PTX within cells due to the direct translocation of CPP/PTX. This drug delivery system exhibits strong capacity for inhibition of tumor growth and offers a new avenue for the development of advanced drug delivery systems for anticancer therapy.

Application of three-dimensional printing for colon targeted drug delivery systems

PubMed Central

Charbe, Nitin B.; McCarron, Paul A.; Lane, Majella E.; Tambuwala, Murtaza M.

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems. PMID:28929046

Application of three-dimensional printing for colon targeted drug delivery systems.

PubMed

Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

Smart Drug Delivery Systems in Cancer Therapy.

PubMed

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

AcademyHealth's Delivery System Science Fellowship: Training Embedded Researchers to Design, Implement, and Evaluate New Models of Care.

PubMed

Kanani, Nisha; Hahn, Erin; Gould, Michael; Brunisholz, Kimberly; Savitz, Lucy; Holve, Erin

2017-07-01

AcademyHealth's Delivery System Science Fellowship (DSSF) provides a paid postdoctoral pragmatic learning experience to build capacity within learning healthcare systems to conduct research in applied settings. The fellowship provides hands-on training and professional leadership opportunities for researchers. Since its inception in 2012, the program has grown rapidly, with 16 health systems participating in the DSSF to date. In addition to specific projects conducted within health systems (and numerous publications associated with those initiatives), the DSSF has made several broader contributions to the field, including defining delivery system science, identifying a set of training objectives for researchers working in delivery systems, and developing a national collaborative network of care delivery organizations, operational leaders, and trainees. The DSSF is one promising approach to support higher-value care by promoting continuous learning and improvement in health systems. © 2017 Society of Hospital Medicine.

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.

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

Intelligent system design for bionanorobots in drug delivery.

PubMed

Fletcher, Mark; Biglarbegian, Mohammad; Neethirajan, Suresh

A nanorobot is defined as any smart structure which is capable of actuation, sensing, manipulation, intelligence, and swarm behavior at the nanoscale. In this study, we designed an intelligent system using fuzzy logic for diagnosis and treatment of tumors inside the human body using bionanorobots. We utilize fuzzy logic and a combination of thermal, magnetic, optical, and chemical nanosensors to interpret the uncertainty associated with the sensory information. Two different fuzzy logic structures, for diagnosis (Mamdani structure) and for cure (Takagi-Sugeno structure), were developed to efficiently identify the tumors and treat them through delivery of effective dosages of a drug. Validation of the designed system with simulated conditions proved that the drug delivery of bionanorobots was robust to reasonable noise that may occur in the bionanorobot sensors during navigation, diagnosis, and curing of the cancer cells. Bionanorobots represent a great hope for successful cancer therapy in the near future.

Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.

PubMed

Cui, Wei; Li, Junbai; Decher, Gero

2016-02-10

Nanostructured drug-carrier systems promise numerous benefits for drug delivery. They can be engineered to precisely control drug-release rates or to target specific sites within the body with a specific amount of therapeutic agent. However, to achieve the best therapeutic effects, the systems should be designed for carrying the optimum amount of a drug to the desired target where it should be released at the optimum rate for a specified time. Despite numerous attempts, fulfilling all of these requirements in a synergistic way remains a huge challenge. The trend in drug delivery is consequently directed toward integrated multifunctional carrier systems, providing selective recognition in combination with sustained or triggered release. Capsules as vesicular systems enable drugs to be confined for controlled release. Furthermore, carriers modified with recognition groups can enhance the capability of encapsulated drug efficacy. Here, recent advances are reviewed regarding designing and preparing assembled capsules with targeting ligands or size controllable for selective recognition in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advanced Space Transportation Concepts and Propulsion Technologies for a New Delivery Paradigm

NASA Technical Reports Server (NTRS)

Robinson, John W.; McCleskey, Carey M.; Rhodes, Russel E.; Lepsch, Roger A.; Henderson, Edward M.; Joyner, Claude R., III; Levack, Daniel J. H.

2013-01-01

This paper describes Advanced Space Transportation Concepts and Propulsion Technologies for a New Delivery Paradigm. It builds on the work of the previous paper "Approach to an Affordable and Productive Space Transportation System". The scope includes both flight and ground system elements, and focuses on their compatibility and capability to achieve a technical solution that is operationally productive and also affordable. A clear and revolutionary approach, including advanced propulsion systems (advanced LOX rich booster engine concept having independent LOX and fuel cooling systems, thrust augmentation with LOX rich boost and fuel rich operation at altitude), improved vehicle concepts (autogeneous pressurization, turbo alternator for electric power during ascent, hot gases to purge system and keep moisture out), and ground delivery systems, was examined. Previous papers by the authors and other members of the Space Propulsion Synergy Team (SPST) focused on space flight system engineering methods, along with operationally efficient propulsion system concepts and technologies. This paper continues the previous work by exploring the propulsion technology aspects in more depth and how they may enable the vehicle designs from the previous paper. Subsequent papers will explore the vehicle design, the ground support system, and the operations aspects of the new delivery paradigm in greater detail.

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

PubMed

Towill, D R; Christopher, M

2005-01-01

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

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.

Designing liposomal adjuvants for the next generation of vaccines.

PubMed

Perrie, Yvonne; Crofts, Fraser; Devitt, Andrew; Griffiths, Helen R; Kastner, Elisabeth; Nadella, Vinod

2016-04-01

Liposomes not only offer the ability to enhance drug delivery, but can effectively act as vaccine delivery systems and adjuvants. Their flexibility in size, charge, bilayer rigidity and composition allow for targeted antigen delivery via a range of administration routes. In the development of liposomal adjuvants, the type of immune response promoted has been linked to their physico-chemical characteristics, with the size and charge of the liposomal particles impacting on liposome biodistribution, exposure in the lymph nodes and recruitment of the innate immune system. The addition of immunostimulatory agents can further potentiate their immunogenic properties. Here, we outline the attributes that should be considered in the design and manufacture of liposomal adjuvants for the delivery of sub-unit and nucleic acid based vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

Hydrazone linkages in pH responsive drug delivery systems.

PubMed

Sonawane, Sandeep J; Kalhapure, Rahul S; Govender, Thirumala

2017-03-01

Stimuli-responsive polymeric drug delivery systems using various triggers to release the drug at the sites have become a major focus area. Among various stimuli-responsive materials, pH-responsiveness has been studied extensively. The materials used for fabricating pH-responsive drug delivery systems include a specific chemical functionality in their structure that can respond to changes in the pH of the surrounding environment. Various chemical functionalities, for example, acetal, amine, ortho ester, amine and hydrazone, have been used to design materials that are capable of releasing their payload at the acidic pH conditions of the tumor or infection sites. Hydrazone linkages are significant synthons for numerous transformations and have gained importance in pharmaceutical sciences due to their various biological and clinical applications. These linkages have been employed in various drug delivery vehicles, such as linear polymers, star shaped polymers, dendrimers, micelles, liposomes and inorganic nanoparticles, for pH-responsive drug delivery. This review paper focuses on the synthesis and characterization methods of hydrazone bond containing materials and their applications in pH-responsive drug delivery systems. It provides detailed suggestions as guidelines to materials and formulation scientists for designing biocompatible pH-responsive materials with hydrazone linkages and identifying future studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Fabrication of core-shell nanofibers for controlled delivery of bromelain and salvianolic acid B for skin regeneration in wound therapeutics.

PubMed

Shoba, Ekambaram; Lakra, Rachita; Syamala Kiran, Manikantan; Korrapati, Purna Sai

2017-06-05

The physiological and pathological complexity of the wound healing process makes it more challenging to design an ideal tissue regeneration scaffold. Precise scaffolding with high drug loading efficiency, efficient intracellular efficacy for therapeutic delivery, minimal nonspecific cellular and blood protein binding, and maximum biocompatibility forms the basis for an ideal delivery system. This paper describes a combinational multiphasic delivery system, where biomolecules are delivered through the fabrication of coaxial electrospinning of different biocompatible polymers. The ratio and specificity of polymers for specific biofunction are optimized and the delivery system is completely characterized with reference to the mechanical property and structural integrity of bromelain (debridement enzyme) and salvianolic acid B (pro-angiogenesis and re-epithelialization). The in vitro release profile illustrated the sustained release of debriding protease and bioactive component in a timely fashion. The fabricated scaffold showed angiogenic potential through in vitro migration of endothelial cells and increased new capillaries from the existing blood vessel in response to an in ovo chicken chorioallantoic membrane assay. In addition, in vivo studies confirm the efficacy of the fabricated scaffold. Our results therefore open up a new avenue for designing a bioactive combinational multiphasic delivery system to enhance wound healing.

Silk-based delivery systems of bioactive molecules.

PubMed

Numata, Keiji; Kaplan, David L

2010-12-30

Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed. Copyright © 2010 Elsevier B.V. All rights reserved.

Fabrication, Physicochemical Characterization, and Performance Evaluation of Biodegradable Polymeric Microneedle Patch System for Enhanced Transcutaneous Flux of High Molecular Weight Therapeutics.

PubMed

Shah, Viral; Choudhury, Bijaya Krushna

2017-11-01

A revolutionary paradigm shift is being observed currently, towards the use of therapeutic biologics for disease management. The present research was focused on designing an efficient dosage form for transdermal delivery of α-choriogonadotropin (high molecular weight biologic), through biodegradable polymeric microneedles. Polyvinylpyrrolidone-based biodegradable microneedle arrays loaded with high molecular weight polypeptide, α-choriogonadotropin, were fabricated for its systemic delivery via transdermal route. Varied process and formulation parameters were optimized for fabricating microneedle array, which in turn was expected to temporally rupture the stratum corneum layer of the skin, acting as a major barrier to drug delivery through transdermal route. The developed polymeric microneedles were optimized on the basis of quality attributes like mechanical strength, axial strength, insertion ratio, and insertion force analysis. The optimized polymeric microneedle arrays were characterized for in vitro drug release studies, ex vivo drug permeation studies, skin resealing studies, and in vivo pharmacokinetic studies. Results depicted that fabricated polymeric microneedle arrays with mechanical strength of above 5 N and good insertion ratio exhibited similar systemic bioavailability of α-choriogonadotropin in comparison to marketed subcutaneous injection formulation of α-choriogonadotropin. Thus, it was ultimately concluded that the designed drug delivery system can serve as an efficient tool for systemic delivery of therapeutic biologics, with an added benefit of overcoming the limitations of parenteral delivery, achieving better patient acceptability and compliance.

Expanding the domain of drug delivery for HIV prevention: exploration of the transdermal route.

PubMed

Puri, Ashana; Sivaraman, Arunprasad; Zhang, Wei; Clark, Meredith R; Banga, Ajay K

2017-01-01

Constant efforts for HIV prevention using antiretroviral drugs, pre- and postexposure prophylactic agents, and microbicides are being made by researchers. Drug-delivery systems such as oral tablets and coitally dependent vaginal gels are short acting, require daily application, and are associated with user adherence issues, whereas the coitally independent systems such as injectables and biodegradable implants are long acting, lasting several months, during which time the termination of prophylaxis is impractical in case of adverse effects. An effective drug-delivery system to be used for an intermediate duration, if available, would be an attractive alternative option for users in terms of adherence. Transdermal delivery systems, overcoming most of the limitations of the other routes of administration and aiming to provide sustained delivery of drugs through skin, may be explored for HIV prevention. Passive and physical enhancement techniques may be designed strategically to improve the transdermal delivery of HIV preventive agents.

NASA develops teleoperator retrieval system

NASA Technical Reports Server (NTRS)

1978-01-01

The teleoperator retrieval system vehicle was designed to reboost and/or deorbit the Skylab; however, usefulness in survey, stabilization, retrieval and delivery was examined. Thrusters, designed for cold gas propulsion, were adapted to hydrazine propulsion. Design specifications and cost analysis are given.

Plant Growth Module (PGM) conceptual design

NASA Technical Reports Server (NTRS)

Schwartzkopf, Steven H.; Rasmussen, Daryl

1987-01-01

The Plant Growth Module for the Controlled Ecological Life Support System (CELSS), designed to answer basic science questions related to growing plants in closed systems, is described functionally with artist's conception drawings. Subsystems are also described, including enclosure and access; data acquisition and control; gas monitor and control; heating, ventilation, and air conditioning; air delivery; nutrient monitor and control; microbial monitoring and control; plant support and nutrient delivery; illumination; and internal operations. The hardware development plan is outlined.

Polymers for Drug Delivery Systems

PubMed Central

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

2012-01-01

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

Systems Analysis and Structural Design of an Unpressurized Cargo Delivery Vehicle

NASA Technical Reports Server (NTRS)

Wu, K. Chauncey; Cruz, Jonathan N.; Antol, Jeffrey; Sasamoto, Washito A.

2007-01-01

The International Space Station will require a continuous supply of replacement parts for ongoing maintenance and repair after the planned retirement of the Space Shuttle in 2010. These parts are existing line-replaceable items collectively called Orbital Replacement Units, and include heavy and oversized items such as Control Moment Gyroscopes and stowed radiator arrays originally intended for delivery aboard the Space Shuttle. Current resupply spacecraft have limited to no capability to deliver these external logistics. In support of NASA's Exploration Systems Architecture Study, a team at Langley Research Center designed an Unpressurized Cargo Delivery Vehicle to deliver bulk cargo to the Space Station. The Unpressurized Cargo Delivery Vehicle was required to deliver at least 13,200 lbs of cargo mounted on at least 18 Flight Releasable Attachment Mechanisms. The Crew Launch Vehicle design recommended in the Exploration Systems Architecture Study would be used to launch one annual resupply flight to the International Space Station. The baseline vehicle design developed here has a cargo capacity of 16,000 lbs mounted on up to 20 Flight Releasable Attachment Mechanisms. Major vehicle components are a 5.5m-diameter cargo module containing two detachable cargo pallets with the payload, a Service Module to provide propulsion and power, and an aerodynamic nose cone. To reduce cost and risk, the Service Module is identical to the one used for the Crew Exploration Vehicle design.

Student Attitudes toward Information Systems Graduate Program Design and Delivery

ERIC Educational Resources Information Center

Thouin, Mark F.; Hefley, William E.; Raghunathan, Srinivasan

2018-01-01

This study examines student preferences regarding graduate management information systems (MIS) education. One hundred and eighty four graduate students responded to a survey exploring student attitudes towards degree program content, delivery format, and peer group interaction. Study results indicate that students prefer a program with an even…

An Information Push-Delivery System Design for Personal Information Service on the Internet.

ERIC Educational Resources Information Center

Chen, Chen-Tung; Tai, Wei-Shen

2003-01-01

Discussion of information overload from the Internet focuses on an information push-delivery system, which applies fuzzy information retrieval and fuzzy similarity measurement to avoid the information overload problem. Describes an empirical investigation conducted with students at Da-Yeh University (Taiwan) that investigated satisfaction with a…

Implementation of wireless power transfer and communications for an implantable ocular drug delivery system.

PubMed

Tang, T B; Smith, S; Flynn, B W; Stevenson, J T M; Gundlach, A M; Reekie, H M; Murray, A F; Renshaw, D; Dhillon, B; Ohtori, A; Inoue, Y; Terry, J G; Walton, A J

2008-09-01

A wireless power transfer and communication system based on near-field inductive coupling has been designed and implemented. The feasibility of using such a system to remotely control drug release from an implantable drug delivery system is addressed. The architecture of the wireless system is described and the signal attenuation over distance in both water and phosphate buffered saline is studied. Additionally, the health risk due to exposure to radio frequency (RF) radiation is examined using a biological model. The experimental results demonstrate that the system can trigger the release of drug within 5 s, and that such short exposure to RF radiation does not produce any significant (

Designing polymers with sugar-based advantages for bioactive delivery applications.

PubMed

Zhang, Yingyue; Chan, Jennifer W; Moretti, Alysha; Uhrich, Kathryn E

2015-12-10

Sugar-based polymers have been extensively explored as a means to increase drug delivery systems' biocompatibility and biodegradation. Here,we review he use of sugar-based polymers for drug delivery applications, with a particular focus on the utility of the sugar component(s) to provide benefits for drug targeting and stimuli responsive systems. Specifically, numerous synthetic methods have been developed to reliably modify naturally-occurring polysaccharides, conjugate sugar moieties to synthetic polymer scaffolds to generate glycopolymers, and utilize sugars as a multifunctional building block to develop sugar-linked polymers. The design of sugar-based polymer systems has tremendous implications on both the physiological and biological properties imparted by the saccharide units and are unique from synthetic polymers. These features include the ability of glycopolymers to preferentially target various cell types and tissues through receptor interactions, exhibit bioadhesion for prolonged residence time, and be rapidly recognized and internalized by cancer cells. Also discussed are the distinct stimuli-sensitive properties of saccharide-modified polymers to mediate drug release under desired conditions. Saccharide-based systems with inherent pH- and temperature-sensitive properties, as well as enzyme-cleavable polysaccharides for targeted bioactive delivery, are covered. Overall, this work emphasizes inherent benefits of sugar-containing polymer systems for bioactive delivery.

A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods

PubMed Central

Chinna Reddy, P; Chaitanya, K.S.C.; Madhusudan Rao, Y.

2011-01-01

Owing to the ease of the administration, the oral cavity is an attractive site for the delivery of drugs. Through this route it is possible to realize mucosal (local effect) and transmucosal (systemic effect) drug administration. In the first case, the aim is to achieve a site-specific release of the drug on the mucosa, whereas the second case involves drug absorption through the mucosal barrier to reach the systemic circulation. The main obstacles that drugs meet when administered via the buccal route derive from the limited absorption area and the barrier properties of the mucosa. The effective physiological removal mechanisms of the oral cavity that take the formulation away from the absorption site are the other obstacles that have to be considered. The strategies studied to overcome such obstacles include the employment of new materials that, possibly, combine mucoadhesive, enzyme inhibitory and penetration enhancer properties and the design of innovative drug delivery systems which, besides improving patient compliance, favor a more intimate contact of the drug with the absorption mucosa. This presents a brief description of advantages and limitations of buccal drug delivery and the anatomical structure of oral mucosa, mechanisms of drug permeation followed by current formulation design in line with developments in buccal delivery systems and methodology in evaluating buccal formulations. PMID:23008684

Transdermal patches: history, development and pharmacology

PubMed Central

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

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.

Solubility enhancement and delivery systems of curcumin a herbal medicine: a review.

PubMed

Hani, Umme; Shivakumar, H G

2014-01-01

Curcumin diferuloylmethane is a main yellow bioactive component of turmeric, possess wide spectrum of biological actions. It was found to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. However, the benefits are curtailed by its extremely poor aqueous solubility, which subsequently limits the bioavailability and therapeutic effects of curcumin. Nanotechnology is the available approach in solving these issues. Therapeutic efficacy of curcumin can be utilized effectively by doing improvement in formulation properties or delivery systems. Numerous attempts have been made to design a delivery system of curcumin. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of curcumin. This review focuses on the methods to increase solubility of curcumin and various nanotechnologies based delivery systems and other delivery systems of curcumin.

Topical drug delivery systems: a patent review.

PubMed

Singh Malik, Deepinder; Mital, Neeraj; Kaur, Gurpreet

2016-01-01

Topical administration is the favored route for local delivery of therapeutic agents due to its convenience and affordability. The specific challenge of designing a therapeutic system is to achieve an optimal concentration of a certain drug at its site of action for an appropriate duration. This review summarizes innovations from the past 3 years (2012-2015) in the field of topical drug delivery for the treatment of local infections of the vagina, nose, eye and skin. The review also throws some light on the anatomy and physiology of these organs and their various defensive barriers which affect the delivery of drugs administered topically. Topical administration has been gaining attention over the last few years. However, conventional topical drug delivery systems suffer from drawbacks such as poor retention and low bioavailability. The successful formulation of topical delivery products requires the careful manipulation of defensive barriers and selection of a soluble drug carrier. Extensive research is required to develop newer topical drug delivery systems aiming either to improve the efficacy or to reduce side effects compared to current patented systems.

Automated Management and Delivery of Distance Courseware.

ERIC Educational Resources Information Center

Johnson, W. Lewis; Blake, Tyler; Shaw, Erin

This paper describes a system called ANDES, designed for the management and delivery of distance education courses. ANDES enables students to study at home at their own pace, as well as interact with instructors and other students in virtual classrooms. It uses World Wide Web technology for transmission and delivery, with extensions relevant to…

Controlled growth factor release from synthetic extracellular matrices

NASA Astrophysics Data System (ADS)

Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

2000-12-01

Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

Adamantane in Drug Delivery Systems and Surface Recognition.

PubMed

Štimac, Adela; Šekutor, Marina; Mlinarić-Majerski, Kata; Frkanec, Leo; Frkanec, Ruža

2017-02-16

The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application.

Magnetophoresis for enhancing transdermal drug delivery: Mechanistic studies and patch design

PubMed Central

Murthy, S. Narasimha; Sammeta, Srinivasa M.; Bower, C.

2017-01-01

Magnetophoresis is a method of enhancement of drug permeation across the biological barriers by application of magnetic field. The present study investigated the mechanistic aspects of magnetophoretic transdermal drug delivery and also assessed the feasibility of designing a magnetophoretic transdermal patch system for the delivery of lidocaine. In vitro drug permeation studies were carried out across the porcine epidermis at different magnetic field strengths. The magnetophoretic drug permeation “flux enhancement factor” was found to increase with the applied magnetic field strength. The mechanistic studies revealed that the magnetic field applied in this study did not modulate permeability of the stratum corneum barrier. The predominant mechanism responsible for magnetically mediated drug permeation enhancement was found to be “magnetokinesis”. The octanol/water partition coefficient of drugs was also found to increase when exposed to the magnetic field. A reservoir type transdermal patch system with a magnetic backing was designed for in vivo studies. The dermal bioavailability (AUC0–6 h) from the magnetophoretic patch system in vivo, in rats was significantly higher than the similarly designed nonmagnetic control patch. PMID:20728484

Early childhood education: Status trends, and issues related to electronic delivery

NASA Technical Reports Server (NTRS)

Rothenberg, D.

1973-01-01

The status of, and trends and issues within, early childhood education which are related to the possibilities of electronic delivery of educational service are considered in a broader investigation of the role of large scale, satellite based educational telecommunications systems. Data are analyzed and trends and issues discussed to provide information useful to the system designer who wishes to identify and assess the opportunities for large scale electronic delivery in early childhood education.

An Academic-Business Partnership for Advancing Clinical Informatics.

ERIC Educational Resources Information Center

Connors, Helen R.; Weaver, Charlotte; Warren, Judith; Miller, Karen L.

2002-01-01

A partnership between a university school of nursing and a health care information technology supplier resulted in the Simulated E-hEalth Delivery System (SEEDS). This program enables nursing students to learn clinical skills in a state-of-the-art environment using a live-production, clinical information system designed for care delivery. (JOW)

Nanoparticles in the clinic

PubMed Central

Anselmo, Aaron C.

2016-01-01

Abstract Nanoparticle/microparticle‐based drug delivery systems for systemic (i.e., intravenous) applications have significant advantages over their nonformulated and free drug counterparts. For example, nanoparticle systems are capable of delivering therapeutics and treating areas of the body that other delivery systems cannot reach. As such, nanoparticle drug delivery and imaging systems are one of the most investigated systems in preclinical and clinical settings. Here, we will highlight the diversity of nanoparticle types, the key advantages these systems have over their free drug counterparts, and discuss their overall potential in influencing clinical care. In particular, we will focus on current clinical trials for nanoparticle formulations that have yet to be clinically approved. Additional emphasis will be on clinically approved nanoparticle systems, both for their currently approved indications and their use in active clinical trials. Finally, we will discuss many of the often overlooked biological, technological, and study design challenges that impact the clinical success of nanoparticle delivery systems. PMID:29313004

Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection.

PubMed

Bear, Joseph C; Patrick, P Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J; Pankhurst, Quentin A; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P; Mayes, Andrew G

2016-09-27

Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it's drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.

Design attributes of long-circulating polymeric drug delivery vehicles.

PubMed

Beck-Broichsitter, Moritz; Nicolas, Julien; Couvreur, Patrick

2015-11-01

Following systemic administration polymeric drug delivery vehicles allow for a controlled and targeted release of the encapsulated medication at the desired site of action. For an elevated and organ specific accumulation of their cargo, nanocarriers need to avoid opsonization, activation of the complement system and uptake by macrophages of the mononuclear phagocyte system. In this respect, camouflaged vehicles revealed a delayed elimination from systemic circulation and an improved target organ deposition. For instance, a steric shielding of the carrier surface by poly(ethylene glycol) substantially decreased interactions with the biological environment. However, recent studies disclosed possible deficits of this approach, where most notably, poly(ethylene glycol)-modified drug delivery vehicles caused significant immune responses. At present, identification of novel potential carrier coating strategies facilitating negligible immune reactions is an emerging field of interest in drug delivery research. Moreover, physical carrier properties including geometry and elasticity seem to be very promising design attributes to surpass numerous biological barriers, in order to improve the efficacy of the delivered medication. Copyright © 2015 Elsevier B.V. All rights reserved.

Hierarchical design of a polymeric nanovehicle for efficient tumor regression and imaging

NASA Astrophysics Data System (ADS)

An, Jinxia; Guo, Qianqian; Zhang, Peng; Sinclair, Andrew; Zhao, Yu; Zhang, Xinge; Wu, Kan; Sun, Fang; Hung, Hsiang-Chieh; Li, Chaoxing; Jiang, Shaoyi

2016-04-01

Effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we designed a hierarchical polymeric nanoparticle structure for anti-cancer chemotherapy delivery by utilizing state-of-the-art polymer chemistry and co-assembly techniques. This novel structural design combines the most desired merits for drug delivery in a single particle, including a long in vivo circulation time, inhibited non-specific cell uptake, enhanced tumor cell internalization, pH-controlled drug release and simultaneous imaging. This co-assembled nanoparticle showed exceptional stability in complex biological media. Benefiting from the synergistic effects of zwitterionic and multivalent galactose polymers, drug-loaded nanoparticles were selectively internalized by cancer cells rather than normal tissue cells. In addition, the pH-responsive core retained their cargo within their polymeric coating through hydrophobic interaction and released it under slightly acidic conditions. In vivo pharmacokinetic studies in mice showed minimal uptake of nanoparticles by the mononuclear phagocyte system and excellent blood circulation half-lives of 14.4 h. As a result, tumor growth was completely inhibited and no damage was observed for normal organ tissues. This newly developed drug nanovehicle has great potential in cancer therapy, and the hierarchical design principle should provide valuable information for the development of the next generation of drug delivery systems.Effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we designed a hierarchical polymeric nanoparticle structure for anti-cancer chemotherapy delivery by utilizing state-of-the-art polymer chemistry and co-assembly techniques. This novel structural design combines the most desired merits for drug delivery in a single particle, including a long in vivo circulation time, inhibited non-specific cell uptake, enhanced tumor cell internalization, pH-controlled drug release and simultaneous imaging. This co-assembled nanoparticle showed exceptional stability in complex biological media. Benefiting from the synergistic effects of zwitterionic and multivalent galactose polymers, drug-loaded nanoparticles were selectively internalized by cancer cells rather than normal tissue cells. In addition, the pH-responsive core retained their cargo within their polymeric coating through hydrophobic interaction and released it under slightly acidic conditions. In vivo pharmacokinetic studies in mice showed minimal uptake of nanoparticles by the mononuclear phagocyte system and excellent blood circulation half-lives of 14.4 h. As a result, tumor growth was completely inhibited and no damage was observed for normal organ tissues. This newly developed drug nanovehicle has great potential in cancer therapy, and the hierarchical design principle should provide valuable information for the development of the next generation of drug delivery systems. Electronic supplementary information (ESI) available: Experimental details, 1H NMR spectra and GPC of polymers. See DOI: 10.1039/c6nr01595f

Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review.

PubMed

Kanamala, Manju; Wilson, William R; Yang, Mimi; Palmer, Brian D; Wu, Zimei

2016-04-01

As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanoparticle drug-delivery systems for peritoneal cancers: a case study of the design, characterization and development of the expansile nanoparticle.

PubMed

Colby, Aaron H; Oberlies, Nicholas H; Pearce, Cedric J; Herrera, Victoria L M; Colson, Yolonda L; Grinstaff, Mark W

2017-05-01

Nanoparticle (NP)-based drug-delivery systems are frequently employed to improve the intravenous administration of chemotherapy; however, few reports explore their application as an intraperitoneal therapy. We developed a pH-responsive expansile nanoparticle (eNP) specifically designed to leverage the intraperitoneal route of administration to treat intraperitoneal malignancies, such as mesothelioma, ovarian, and pancreatic carcinomatoses. This review describes the design, evaluation, and evolution of the eNP technology and, specifically, a Materials-Based Targeting paradigm that is unique among the many active- and passive-targeting strategies currently employed by NP-delivery systems. pH-responsive eNP swelling is responsible for the extended residence at the target tumor site as well as the subsequent improvement in tumoral drug delivery and efficacy observed with paclitaxel-loaded eNPs (PTX-eNPs) compared to the standard clinical formulation of paclitaxel, Taxol®. Superior PTX-eNP efficacy is demonstrated in two different orthotopic models of peritoneal cancer-mesothelioma and ovarian cancer; in a third model-of pancreatic cancer-PTX-eNPs demonstrated comparable efficacy to Taxol with reduced toxicity. Furthermore, the unique structural and responsive characteristics of eNPs enable them to be used in three additional treatment paradigms, including: treatment of lymphatic metastases in breast cancer; use as a highly fluorescent probe to visually guide the resection of peritoneal implants; and, in a two-step delivery paradigm for concentrating separately administered NP and drug at a target site. This case study serves as an important example of using the targeted disease-state's pathophysiology to inform the NP design as well as the method of use of the delivery system. WIREs Nanomed Nanobiotechnol 2017, 9:e1451. doi: 10.1002/wnan.1451 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Pathogen-mimicking vaccine delivery system designed with a bioactive polymer (inulin acetate) for robust humoral and cellular immune responses.

PubMed

Kumar, Sunny; Kesharwani, Siddharth S; Kuppast, Bhimanna; Bakkari, Mohammed Ali; Tummala, Hemachand

2017-09-10

New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired. Copyright © 2017 Elsevier B.V. All rights reserved.

Behavioral System Feedback Measurement Failure: Sweeping Quality under the Rug

ERIC Educational Resources Information Center

Mihalic, Maria T.; Ludwig, Timothy D.

2009-01-01

Behavioral Systems rely on valid measurement systems to manage processes and feedback and to deliver contingencies. An examination of measurement system components designed to track customer service quality of furniture delivery drivers revealed the measurement system failed to capture information it was designed to measure. A reason for this…

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.

Design and optimization of a flexible high-peak-power laser-to-fiber coupled illumination system used in digital particle image velocimetry

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

Robinson, Ronald A.; Ilev, Ilko K.

We present a study on the design and parameter optimization of a flexible high-peak-power fiber-optic laser delivery system using commercially available solid-core silica fibers and an experimental glass hollow waveguide (HW). The fiber-optic delivery system provides a flexible, safe, and easily and precisely positioned laser irradiation for many applications including uniform illumination for digital particle image velocimetry (DPIV). The delivery fibers, when coupled through a line-generating lens, produce a uniform thin laser sheet illumination for accurate and repeatable DPIV two-dimensional velocity measurements. We report experimental results on homogenizing the laser beam profile using various mode-mixing techniques. Furthermore, because a fundamentalmore » problem for fiber-optic-based high-peak-power laser delivery systems is the possible damage effects of the fiber material, we determine experimentally the peak power density damage threshold of various delivery fibers designed for the visible spectral range at a typical DPIV laser wavelength of 532 nm. In the case of solid-core silica delivery fibers using conventional lens-based laser-to-fiber coupling, the damage threshold varies from 3.7 GW/cm{sup 2} for a 100-{mu}m-core-diameter high-temperature fiber to 3.9 GW/cm{sup 2} for a 200-{mu}m-core-diameter high-power delivery fiber, with a total output laser energy delivered of at least 3-10 mJ for those respective fibers. Therefore, these fibers are marginally suitable for most macro-DPIV applications. However, to improve the high-power delivery capability for close-up micro-DPIV applications, we propose and validate an experimental fiber link with much higher laser power delivery capability than the solid-core fiber links. We use an uncoated grazing-incidence-based tapered glass funnel coupled to a glass HW with hollow air-core diameter of 700 {mu}m, a low numerical aperture of 0.05, and a thin inside cladding of cyclic olefin polymer coating for optimum transmission at 532 nm. Because of the mode homogenizing effect and lower power density, the taper-waveguide laser delivery technique ensured high damage threshold for the delivery HW, and as a result, no damage occurred at the maximum measured input laser energy of 33 mJ used in this study.« less

Global Positioning System (GPS) and Geographic Information System (GIS) analysis of mobile harvesting equipment and sediment delivery to streams during forest harvest operations on steep terrain: Experimental design

Treesearch

Daniel Bowker; Jeff Stringer; Chris Barton; Songlin Fei

2011-01-01

Sediment mobilized by forest harvest machine traffic contributes substantially to the degradation of headwater stream systems. This study monitored forest harvest machine traffic to analyze how it affects sediment delivery to stream channels. Harvest machines were outfitted with global positioning system (GPS) dataloggers, recording machine movements and working status...

Multifunctional quantum dots and liposome complexes in drug delivery

PubMed Central

Wang, Qi; Chao, Yimin

2018-01-01

Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches. PMID:28866655

Multifunctional quantum dots and liposome complexes in drug delivery.

PubMed

Wang, Qi; Chao, Yi-Min

2017-09-03

Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches.

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

NASA Technical Reports Server (NTRS)

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

1990-01-01

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

Primary Intravenous Set Consumption Across 3 Branded Infusion Pumps

PubMed Central

Hedlund, Nancy; Sarangpur, Shishir; Kayler, Shannon; O'Brien, Kathy

2017-01-01

This retrospective study of 6426 hip replacement, coronary artery bypass graft, and colectomy surgeries across 23 US hospitals found that intravenous (IV) set designs that can be interchanged for use both in gravity-fed and automated pump delivery systems are replaced less frequently than IV sets designed for use primarily by one delivery method. Semistructured interviews with nurses highlighted the impact of set design on nursing workflow when moving between gravity-fed and pump-based administration. Use of interchangeable, single-design IV sets across gravity and automated infusions minimizes disruptions to closed systems, may reduce nurses being distracted from patients' clinical needs when replacing sets, and may yield supply cost savings. PMID:28682999

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.

Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries

DTIC Science & Technology

2016-09-01

Invited seminar: “Ocular Drug Delivery Nanowafer: Design and Applications,” Houston Methodist Research Institute, Houston, TX. Date: 08-08-2016. Books... Designed the experiments, reviewed and analyzed the experimental results. Funding Support Cystinosis Research Foundation, DOD Name Daniela...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for

Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances

PubMed Central

Xu, Shi; Olenyuk, Bogdan Z.; Okamoto, Curtis T.; Hamm-Alvarez, Sarah F.

2012-01-01

Targeting of drugs and their carrier systems by using receptor-mediated endocytotic pathways was in its nascent stages 25 years ago. In the intervening years, an explosion of knowledge focused on design and synthesis of nanoparticulate delivery systems as well as elucidation of the cellular complexity of what was previously-termed receptor-mediated endocytosis has now created a situation when it has become possible to design and test the feasibility of delivery of highly specific nanoparticle drug carriers to specific cells and tissue. This review outlines the mechanisms governing the major modes of receptor-mediated endocytosis used in drug delivery and highlights recent approaches using these as targets for in vivo drug delivery of nanoparticles. The review also discusses some of the inherent complexity associated with the simple shift from a ligand-drug conjugate versus a ligand-nanoparticle conjugate, in terms of ligand valency and its relationship to the mode of receptor-mediated internalization. PMID:23026636

Lipid and polymeric carrier-mediated nucleic acid delivery

PubMed Central

Zhu, Lin; Mahato, Ram I

2010-01-01

Importance of the field Nucleic acids such as plasmid DNA, antisense oligonucleotide, and RNA interference (RNAi) molecules, have a great potential to be used as therapeutics for the treatment of various genetic and acquired diseases. To design a successful nucleic acid delivery system, the pharmacological effect of nucleic acids, the physiological condition of the subjects or sites, and the physicochemical properties of nucleic acid and carriers have to be thoroughly examined. Areas covered in this review The commonly used lipids, polymers and corresponding delivery systems are reviewed in terms of their characteristics, applications, advantages and limitations. What the reader will gain This article aims to provide an overview of biological barriers and strategies to overcome these barriers by properly designing effective synthetic carriers for nucleic acid delivery. Take home message A thorough understanding of biological barriers and the structure–activity relationship of lipid and polymeric carriers is the key for effective nucleic acid therapy. PMID:20836625

Multidisciplinary perspectives for Alzheimer's and Parkinson's diseases: hydrogels for protein delivery and cell-based drug delivery as therapeutic strategies.

PubMed

Giordano, Carmen; Albani, Diego; Gloria, Antonio; Tunesi, Marta; Batelli, Sara; Russo, Teresa; Forloni, Gianluigi; Ambrosio, Luigi; Cigada, Alberto

2009-12-01

This review presents two intriguing multidisciplinary strategies that might make the difference in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The first proposed strategy is based on the controlled delivery of recombinant proteins known to play a key role in these neurodegenerative disorders that are released in situ by optimized polymer-based systems. The second strategy is the use of engineered cells, encapsulated and delivered in situ by suitable polymer-based systems, that act as drug reservoirs and allow the delivery of selected molecules to be used in the treatment of Alzheimer's and Parkinson's diseases. In both these scenarios, the design and development of optimized polymer-based drug delivery and cell housing systems for central nervous system applications represent a key requirement. Materials science provides suitable hydrogel-based tools to be optimized together with suitably designed recombinant proteins or drug delivering-cells that, once in situ, can provide an effective treatment for these neurodegenerative disorders. In this scenario, only interdisciplinary research that fully integrates biology, biochemistry, medicine and materials science can provide a springboard for the development of suitable therapeutic tools, not only for the treatment of Alzheimer's and Parkinson's diseases but also, prospectively, for a wide range of severe neurodegenerative disorders.

Encapsulation, protection, and delivery of bioactive proteins and peptides using nanoparticle and microparticle systems: A review.

PubMed

McClements, David Julian

2018-03-01

There are many examples of bioactive proteins and peptides that would benefit from oral delivery through functional foods, supplements, or medical foods, including hormones, enzymes, antimicrobials, vaccines, and ACE inhibitors. However, many of these bioactive proteins are highly susceptible to denaturation, aggregation or hydrolysis within commercial products or inside the human gastrointestinal tract (GIT). Moreover, many bioactive proteins have poor absorption characteristics within the GIT. Colloidal systems, which contain nanoparticles or microparticles, can be designed to encapsulate, retain, protect, and deliver bioactive proteins. For instance, a bioactive protein may have to remain encapsulated and stable during storage and passage through the mouth and stomach, but then be released within the small intestine where it can be absorbed. This article reviews the application of food-grade colloidal systems for oral delivery of bioactive proteins, including microemulsions, emulsions, nanoemulsions, solid lipid nanoparticles, multiple emulsions, liposomes, and microgels. It also provides a critical assessment of the characteristics of colloidal particles that impact the effectiveness of protein delivery systems, such as particle composition, size, permeability, interfacial properties, and stability. This information should be useful for the rational design of medical foods, functional foods, and supplements for effective oral delivery of bioactive proteins. Copyright © 2018 Elsevier B.V. All rights reserved.

Drug self-delivery systems for cancer therapy.

PubMed

Qin, Si-Yong; Zhang, Ai-Qing; Cheng, Si-Xue; Rong, Lei; Zhang, Xian-Zheng

2017-01-01

Carrier-assistant drug delivery systems (DDSs) have been rapidly established for cancer therapy and great strides have been made in recent years. However, further development of DDSs is retarded by the aspects such as the low drug carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. Drug self-delivery systems (DSDSs), in which active drugs exhibit nanoscale characteristic to realize intracellular delivery by themselves without the help of nanocarriers, have been rapidly developed to address these issues. In this review, we present a comprehensive summary of the recent advances in DSDSs for cancer therapy. After a brief introduction to the major types of DSDSs and their fabrication strategies, we emphatically discuss some representative achievements of these DSDSs for passive or/and positive targeting therapy, combinational therapy as well as theranostics. The design principle is explained and justified, which can cast a new light on developing drug delivery systems for cancer treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

3D treatment planning systems.

PubMed

Saw, Cheng B; Li, Sicong

2018-01-01

Three-dimensional (3D) treatment planning systems have evolved and become crucial components of modern radiation therapy. The systems are computer-aided designing or planning softwares that speed up the treatment planning processes to arrive at the best dose plans for the patients undergoing radiation therapy. Furthermore, the systems provide new technology to solve problems that would not have been considered without the use of computers such as conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). The 3D treatment planning systems vary amongst the vendors and also the dose delivery systems they are designed to support. As such these systems have different planning tools to generate the treatment plans and convert the treatment plans into executable instructions that can be implemented by the dose delivery systems. The rapid advancements in computer technology and accelerators have facilitated constant upgrades and the introduction of different and unique dose delivery systems than the traditional C-arm type medical linear accelerators. The focus of this special issue is to gather relevant 3D treatment planning systems for the radiation oncology community to keep abreast of technology advancement by assess the planning tools available as well as those unique "tricks or tips" used to support the different dose delivery systems. Copyright © 2018 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Design and evaluation of an oral multiparticulate system for dual delivery of amoxicillin and Lactobacillus acidophilus.

PubMed

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

2016-09-01

A delayed-release dual delivery system for amoxicillin and the probiotic Lactobacillus acidophilus was developed and evaluated. Statistical optimization of a cross-linked denatured ovalbumin protective matrix was first synthesized using a Box-Behnken experimental design prior to encapsulation with glyceryl monostereate. The encapsulated ovalbumin matrix was thereafter incorporated with amoxicillin in a gastro-resistant capsule. In vitro characterization and stability analysis of the ovalbumin and encapsulated components were also performed Results: Protection of L. acidophilus probiotic against the bactericidal effects of amoxicillin within the dual formulation was determined. The dual formulation in this study proved effective and provides insight into current microbiome research to identify, classify and use functional healthy bacteria to develop novel probiotic delivery technologies.

SU-F-T-149: Development of the Monte Carlo Simulation Platform Using Geant4 for Designing Heavy Ion Therapy Beam Nozzle

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

Shin, Jae-ik; Yoo, SeungHoon; Cho, Sungho

Purpose: The significant issue of particle therapy such as proton and carbon ion was a accurate dose delivery from beam line to patient. For designing the complex delivery system, Monte Carlo simulation can be used for the simulation of various physical interaction in scatters and filters. In this report, we present the development of Monte Carlo simulation platform to help design the prototype of particle therapy nozzle and performed the Monte Carlo simulation using Geant4. Also we show the prototype design of particle therapy beam nozzle for Korea Heavy Ion Medical Accelerator (KHIMA) project in Korea Institute of Radiological andmore » Medical Science(KIRAMS) at Republic of Korea. Methods: We developed a simulation platform for particle therapy beam nozzle using Geant4. In this platform, the prototype nozzle design of Scanning system for carbon was simply designed. For comparison with theoretic beam optics, the beam profile on lateral distribution at isocenter is compared with Mont Carlo simulation result. From the result of this analysis, we can expected the beam spot property of KHIMA system and implement the spot size optimization for our spot scanning system. Results: For characteristics study of scanning system, various combination of the spot size from accerlator with ridge filter and beam monitor was tested as simple design for KHIMA dose delivery system. Conclusion: In this report, we presented the part of simulation platform and the characteristics study. This study is now on-going in order to develop the simulation platform including the beam nozzle and the dose verification tool with treatment planning system. This will be presented as soon as it is become available.« less

A Critical Review of Instructional Design Process of Distance Learning System

ERIC Educational Resources Information Center

Chaudry, Muhammad Ajmal; ur-Rahman, Fazal

2010-01-01

Instructional design refers to planning, development, delivery and evaluation of instructional system. It is an applied field of study aiming at the application of descriptive research outcomes in regular instructional settings. The present study was designed to critically review the process of instructional design at Allama Iqbal Open University…

Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery.

PubMed

Zhao, Chun-Xia

2013-11-01

Considerable effort has been directed towards developing novel drug delivery systems. Microfluidics, capable of generating monodisperse single and multiple emulsion droplets, executing precise control and operations on these droplets, is a powerful tool for fabricating complex systems (microparticles, microcapsules, microgels) with uniform size, narrow size distribution and desired properties, which have great potential in drug delivery applications. This review presents an overview of the state-of-the-art multiphase flow microfluidics for the production of single emulsions or multiple emulsions for drug delivery. The review starts with a brief introduction of the approaches for making single and multiple emulsions, followed by presentation of some potential drug delivery systems (microparticles, microcapsules and microgels) fabricated in microfluidic devices using single or multiple emulsions as templates. The design principles, manufacturing processes and properties of these drug delivery systems are also discussed and compared. Furthermore, drug encapsulation and drug release (including passive and active controlled release) are provided and compared highlighting some key findings and insights. Finally, site-targeting delivery using multiphase flow microfluidics is also briefly introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes.

PubMed

Zaher, A; Li, S; Wolf, K T; Pirmoradi, F N; Yassine, O; Lin, L; Khashab, N M; Kosel, J

2015-09-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5-2 μg/h for higher release rate designs, and 12-40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

PubMed Central

Zaher, A.; Li, S.; Wolf, K. T.; Pirmoradi, F. N.; Yassine, O.; Lin, L.; Khashab, N. M.; Kosel, J.

2015-01-01

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source. PMID:26487899

Effectiveness of an Alternative Delivery System for In-Service Vocational Teacher Education. Final Report.

ERIC Educational Resources Information Center

Richardson, Donald L.; And Others

The project was designed to provide vocational teacher educators in Colorado with an alternative delivery system for inservice vocational teacher education which would overcome barriers of distance (and difficult winter travel), expense, and low student density. A task force composed of staff members of the State Board for Community Colleges and…

Education of the handicapped child: Status, trend, and issues related to electronic delivery

NASA Technical Reports Server (NTRS)

Rothenberg, D.

1973-01-01

This study is part of a broader investigation of the role of large-scale educational telecommunications systems. Thus, data are analyzed and trends and issues discussed to provide information useful to the systems designer who wishes to identify and assess the opportunities for large-scale electronic delivery of education for the handicapped.

Mobile System for Precise Aero Delivery with Global Reach Network Capability

DTIC Science & Technology

2009-08-30

No intention / need for taking advantage of networking with other agents. The Atair’s Onyx Micro Light ( Onyx ML) delivery system (www.atair.com... onyx ) (Fig.9a) is a precision airdrop system designed to address the requirements of the Joint Precision Airdrop System MLW (JPADS-MLW) system of the...autonomous powered paraglider (LEAPP) developed under contract with DARPA (Fig.9b). a) b) Fig. 9. Onyx ML with mock sensor payload release

CPAS Parachute Testing, Model Development, & Verification

NASA Technical Reports Server (NTRS)

Romero, Leah M.

2013-01-01

Capsule Parachute Assembly System (CPAS) is the human rated parachute system for the Orion vehicle used during re-entry. Similar to Apollo parachute design. Human rating requires additional system redundancy. A Government Furnished Equipment (GFE) project responsible for: Design; Development testing; Performance modeling; Fabrication; Qualification; Delivery

Protein instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release.

PubMed

Jiskoot, Wim; Randolph, Theodore W; Volkin, David B; Middaugh, C Russell; Schöneich, Christian; Winter, Gerhard; Friess, Wolfgang; Crommelin, Daan J A; Carpenter, John F

2012-03-01

Protein instability and immunogenicity are two main roadblocks to the clinical success of novel protein drug delivery systems. In this commentary, we discuss the need for more extensive analytical characterization in relation to concerns about protein instability in injectable drug delivery systems for sustained release. We then will briefly address immunogenicity concerns and outline current best practices for using state-of-the-art analytical assays to monitor protein stability for both conventional and novel therapeutic protein dosage forms. Next, we provide a summary of the stresses on proteins arising during preparation of drug delivery systems and subsequent in vivo release. We note the challenges and difficulties in achieving the absolute requirement of quantitatively assessing the degradation of protein molecules in a drug delivery system. We describe the potential roles for academic research in further improving protein stability and developing new analytical technologies to detect protein degradation byproducts in novel drug delivery systems. Finally, we provide recommendations for the appropriate approaches to formulation design and assay development to ensure that stable, minimally immunogenic formulations of therapeutic proteins are created. These approaches should help to increase the probability that novel drug delivery systems for sustained protein release will become more readily available as effective therapeutic agents to treat and benefit patients. Copyright © 2011 Wiley Periodicals, Inc.

Novel drug delivery systems for glaucoma

PubMed Central

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

2011-01-01

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

Drug delivery systems and materials for wound healing applications.

PubMed

Saghazadeh, Saghi; Rinoldi, Chiara; Schot, Maik; Kashaf, Sara Saheb; Sharifi, Fatemeh; Jalilian, Elmira; Nuutila, Kristo; Giatsidis, Giorgio; Mostafalu, Pooria; Derakhshandeh, Hossein; Yue, Kan; Swieszkowski, Wojciech; Memic, Adnan; Tamayol, Ali; Khademhosseini, Ali

2018-04-05

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. Copyright © 2018 Elsevier B.V. All rights reserved.

Recent trends in drug delivery system using protein nanoparticles.

PubMed

Sripriyalakshmi, S; Jose, Pinkybel; Ravindran, Aswathy; Anjali, C H

2014-09-01

Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems.

Transdermal patches: history, development and pharmacology.

PubMed

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-05-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. © 2015 The British Pharmacological Society.

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

PubMed

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

Nanocomposite Hydrogels: 3D Polymer-Nanoparticle Synergies for On-Demand Drug Delivery.

PubMed

Merino, Sonia; Martín, Cristina; Kostarelos, Kostas; Prato, Maurizio; Vázquez, Ester

2015-05-26

Considerable progress in the synthesis and technology of hydrogels makes these materials attractive structures for designing controlled-release drug delivery systems. In particular, this review highlights the latest advances in nanocomposite hydrogels as drug delivery vehicles. The inclusion/incorporation of nanoparticles in three-dimensional polymeric structures is an innovative means for obtaining multicomponent systems with diverse functionality within a hybrid hydrogel network. Nanoparticle-hydrogel combinations add synergistic benefits to the new 3D structures. Nanogels as carriers for cancer therapy and injectable gels with improved self-healing properties have also been described as new nanocomposite systems.

Nanotechnology inspired advanced engineering fundamentals for optimizing drug delivery.

PubMed

Kassem, Ahmed Alaa

2018-02-06

Drug toxicity and inefficacy are commonly experienced problems with drug therapy failure. To face these problems, extensive research work took place aiming to design new dosage forms for drug delivery especially nanoparticulate systems. These systems are designed to increase the quantity of the therapeutic molecule delivered to the desired site concurrently with reduced side effects. In order to achieve this objective, nanocarriers must principally display suitable drug vehiculization abilities and a controlled biological destiny of drug molecules. Only the intelligent design of the nanomedicine will accomplish these fundamentals. The present review article is dedicated to the discussion of the important fundamentals to be considered in the fabrication of nanomedicines. These include the therapeutic agent, the nanocarrier and the functionalization moieties. Special consideration is devoted to the explanation and compilation of highly potential fabrication approaches assisting how to control the in vivo destiny of the nanomedicine. Finally, some nanotechnology-based drug delivery systems, for the development of nanomedicine, are also discussed. The nanotechnology-based drug delivery systems showed remarkable outcomes based on passive and active targeting as well as improvement of the drug pharmacodynamic and pharmacokinetic profiles. Multifunctional nanocarrier concept affords a revolutionary drug delivery approach for maximizing the efficacy, safety and monitoring the biological fate of the therapeutic molecule. Nanomedicines may enhance the efficacy of therapeutic molecules and reduce their toxic effects. Meanwhile, further research works are required to rightly optimize (and define) the effectiveness, nanotoxicity, in vivo destiny and feasibility of these nanomedicines which, from a preclinical standpoint, are actually promising. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microbially synthesized modular virus-like particles and capsomeres displaying group A streptococcus hypervariable antigenic determinants.

PubMed

Chuan, Yap P; Wibowo, Nani; Connors, Natalie K; Wu, Yang; Hughes, Fiona K; Batzloff, Michael R; Lua, Linda H L; Middelberg, Anton P J

2014-06-01

Effective and low-cost vaccines are essential to control severe group A streptococcus (GAS) infections prevalent in low-income nations and the Australian aboriginal communities. Highly diverse and endemic circulating GAS strains mandate broad-coverage and customized vaccines. This study describes an approach to deliver cross-reactive antigens from endemic GAS strains using modular virus-like particle (VLP) and capsomere systems. The antigens studied were three heterologous N-terminal peptides (GAS1, GAS2, and GAS3) from the GAS surface M-protein that are specific to endemic strains in Australia Northern Territory Aboriginal communities. In vivo data presented here demonstrated salient characteristics of the modular delivery systems in the context of GAS vaccine design. First, the antigenic peptides, when delivered by unadjuvanted modular VLPs or adjuvanted capsomeres, induced high titers of peptide-specific IgG antibodies (over 1 × 10(4) ). Second, delivery by capsomere was superior to VLP for one of the peptides investigated (GAS3), demonstrating that the delivery system relative effectiveness was antigen-dependant. Third, significant cross-reactivity of GAS2-induced IgG with GAS1 was observed using either VLP or capsomere, showing the possibility of broad-coverage vaccine design using these delivery systems and cross-reactive antigens. Fourth, a formulation containing three pre-mixed modular VLPs, each at a low dose of 5 μg (corresponding to <600 ng of each GAS peptide), induced significant titers of IgGs specific to each peptide, demonstrating that a multivalent, broad-coverage VLP vaccine formulation was possible. In summary, the modular VLPs and capsomeres reported here demonstrate, with promising preliminary data, innovative ways to design GAS vaccines using VLP and capsomere delivery systems amenable to microbial synthesis, potentially adoptable by developing countries. © 2013 Wiley Periodicals, Inc.

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

PubMed

Demetzos, Costas

2015-06-01

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

Barriers to Liposomal Gene Delivery: from Application Site to the Target.

PubMed

Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

2016-01-01

Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.

Military Handbook: Management and Design Guidance Electromagnetic Radiation Hardness for Air Launched Ordnance Systems

DTIC Science & Technology

1981-01-15

system is attacted to the delivery aircraft until it Impacto a target, it is exposed to electromagnetic radiation from emitters aboard the delivery...homogeneous, isotropic, ambient medium may be a lossy dielectric. Antenna computations include cur- rent distribution, input impedance, radiation...permissible ambient interference level in the system, and when determining the expected signal-to-inter- ference ratio of the signal transmission circuits

pH-Sensitive stimulus-responsive nanocarriers for targeted delivery of therapeutic agents

PubMed Central

Karimi, Mahdi; Eslami, Masoud; Sahandi-Zangabad, Parham; Mirab, Fereshteh; Farajisafiloo, Negar; Shafaei, Zahra; Ghosh, Deepanjan; Bozorgomid, Mahnaz; Dashkhaneh, Fariba; Hamblin, Michael R.

2016-01-01

In recent years miscellaneous smart micro/nanosystems that respond to various exogenous/endogenous stimuli including temperature, magnetic/electric field, mechanical force, ultrasound/light irradiation, redox potentials, and biomolecule concentration have been developed for targeted delivery and release of encapsulated therapeutic agents such as drugs, genes, proteins, and metal ions specifically at their required site of action. Owing to physiological differences between malignant and normal cells, or between tumors and normal tissues, pH-sensitive nanosystems represent promising smart delivery vehicles for transport and delivery of anticancer agents. Furthermore, pH-sensitive systems possess applications in delivery of metal ions and biomolecules such as proteins, insulin, etc., as well as co-delivery of cargos, dual pH-sensitive nanocarriers, dual/multi stimuli-responsive nanosystems, and even in the search for new solutions for therapy of diseases such as Alzheimer’s. In order to design an optimized system, it is necessary to understand the various pH-responsive micro/nanoparticles and the different mechanisms of pH-sensitive drug release. This should be accompanied by an assessment of the theoretical and practical challenges in the design and use of these carriers. PMID:26762467

[Integrated delivery systems in California--success and failure determining factors for the first 10 years and impetus for Germany].

PubMed

Janus, K; Amelung, V E

2004-10-01

Since the coming into effect of the Health Care Modernization Act (Gesundheitsmodernisierungsgesetz) the conditions for integrated health care delivery are favourable in Germany. However, comprehensive approaches are a long time in coming. In contrast, integrated health care delivery as an integral part of the spreading of managed care entered a further stage of development, which enables health care decision makers to draw conclusions regarding the further development of integrated health care delivery in Germany. Based on case studies integrated delivery systems in the San Francisco Bay Area have been analyzed with the objective to evaluate pitfalls and successful strategies for integrated health care delivery. The major pitfalls refer to an insufficient local focus, a lack of actual integration and the application of per capita reimbursement (which is a key subject on the political agenda in Germany as well) within integrated delivery systems. On the contrary, successful strategies include achieving a dynamic tension between centralized and decentralized coordination, internal and external relationship management, well organised human resource management including a well-defined corporate policy and a comprehensive implementation of information technology. Based on US experiences with integrated delivery systems implications for the design of integrated health care delivery in Germany are discussed.

Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism

PubMed Central

Yaseen, Mohammad A.; Srinivasan, Vivek J.; Gorczynska, Iwona; Fujimoto, James G.; Boas, David A.; Sakadžić, Sava

2015-01-01

Improving our understanding of brain function requires novel tools to observe multiple physiological parameters with high resolution in vivo. We have developed a multimodal imaging system for investigating multiple facets of cerebral blood flow and metabolism in small animals. The system was custom designed and features multiple optical imaging capabilities, including 2-photon and confocal lifetime microscopy, optical coherence tomography, laser speckle imaging, and optical intrinsic signal imaging. Here, we provide details of the system’s design and present in vivo observations of multiple metrics of cerebral oxygen delivery and energy metabolism, including oxygen partial pressure, microvascular blood flow, and NADH autofluorescence. PMID:26713212

Relational coordination promotes quality of chronic care delivery in Dutch disease-management programs.

PubMed

Cramm, Jane Murray; Nieboer, Anna Petra

2012-01-01

Previous studies have shown that relational coordination is positively associated with the delivery of hospital care, acute care, emergency care, trauma care, and nursing home care. The effect of relational coordination in primary care settings, such as disease-management programs, remains unknown. This study examined relational coordination between general practitioners and other professionals in disease-management programs and assessed the impact of relational coordination on the delivery of chronic illness care. Professionals (n = 188; response rate = 57%) in 19 disease-management programs located throughout the Netherlands completed surveys that assessed relational coordination and chronic care delivery. We used a cross-sectional study design. Our study demonstrated that the delivery of chronic illness care was positively related to relational coordination. We found positive relationships with community linkages (r = .210, p < .01), self-management support (r = .217, p < .01), decision support (r = .190, p < .01), delivery system design (r = .278, p < .001), and clinical information systems (r = .193, p < .01). Organization of the health delivery system was not significantly related to relational coordination. The regression analyses showed that even after controlling for all background variables, relational coordination still significantly affected chronic care delivery (β = .212, p ≤ .01). As expected, our findings showed a lower degree of relational coordination among general practitioners than between general practitioners and other core disease-management team members: practice nurses (M = 2.69 vs. 3.73; p < .001), dieticians (M = 2.69 vs. 3.07; p < .01), physical therapists (M = 2.69 vs. 3.06; p < .01), medical specialists (M = 2.69 vs. 3.16; p < .01), and nurse practitioners (M = 2.69 vs. 3.19; p < .001). The enhancement of relational coordination among core disease-management professionals with different disciplines is expected to improve chronic illness care delivery.

Nanobiotechnology: Cell Membrane-Based Delivery Systems.

PubMed

Zhang, Pengfei; Liu, Gang; Chen, Xiaoyuan

2017-04-01

The increasingly rapid pace of research in the field of bioinspired drug delivery systems is revealing the promise of cell membrane-based nanovesicles for biomedical applications. Those cell membrane-based nanoparticles combine the natural functionalities of cell plasma membranes and the bioengineering flexibility of synthetic nanomaterials, and such versatility provides a means of designing exciting new drug formulations for personalized treatment in future nanomedicine.

Polymer-lipid hybrid systems: merging the benefits of polymeric and lipid-based nanocarriers to improve oral drug delivery.

PubMed

Rao, Shasha; Prestidge, Clive A

2016-01-01

A number of biobarriers limit efficient oral drug absorption; both polymer-based and lipid-based nanocarriers have demonstrated properties and delivery mechanisms to overcome these biobarriers in preclinical settings. Moreover, in order to address the multifaceted oral drug delivery challenges, polymer-lipid hybrid systems are now being designed to merge the beneficial features of both polymeric and lipid-based nanocarriers. Recent advances in the development of polymer-lipid hybrids with a specific focus on their viability in oral delivery are reviewed. Three classes of polymer-lipid hybrids have been identified, i.e. lipid-core polymer-shell systems, polymer-core lipid-shell systems, and matrix-type polymer-lipid hybrids. We focus on their application to overcome the various biological barriers to oral drug absorption, as exemplified by selected preclinical studies. Numerous studies have demonstrated the superiority of polymer-lipid hybrid systems to their non-hybrid counterparts in providing improved drug encapsulation, modulated drug release, and improved cellular uptake. These features have encouraged their applications in the delivery of chemotherapeutics, proteins, peptides, and vaccines. With further research expected to optimize the manufacturing and scaling up processes and in-depth pre-clinical pharmacological and toxicological assessments, these multifaceted drug delivery systems will have significant clinical impact on the oral delivery of pharmaceuticals and biopharmaceuticals.

Using CASE Software to Teach Undergraduates Systems Analysis and Design.

ERIC Educational Resources Information Center

Wilcox, Russell E.

1988-01-01

Describes the design and delivery of a college course for information system students utilizing a Computer-Aided Software Engineering program. Discusses class assignments, cooperative learning, student attitudes, and the advantages of using this software in the course. (CW)

Microencapsulation: A promising technique for controlled drug delivery.

PubMed

Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

2010-07-01

MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

Microencapsulation: A promising technique for controlled drug delivery

PubMed Central

Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

2010-01-01

Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

Magnetic Nanoparticles for Multi-Imaging and Drug Delivery

PubMed Central

Lee, Jae-Hyun; Kim, Ji-wook; Cheon, Jinwoo

2013-01-01

Various bio-medical applications of magnetic nanoparticles have been explored during the past few decades. As tools that hold great potential for advancing biological sciences, magnetic nanoparticles have been used as platform materials for enhanced magnetic resonance imaging (MRI) agents, biological separation and magnetic drug delivery systems, and magnetic hyperthermia treatment. Furthermore, approaches that integrate various imaging and bioactive moieties have been used in the design of multi-modality systems, which possess synergistically enhanced properties such as better imaging resolution and sensitivity, molecular recognition capabilities, stimulus responsive drug delivery with on-demand control, and spatio-temporally controlled cell signal activation. Below, recent studies that focus on the design and synthesis of multi-mode magnetic nanoparticles will be briefly reviewed and their potential applications in the imaging and therapy areas will be also discussed. PMID:23579479

Learner Assessment Methods Using a Computer Based Interactive Videodisc System.

ERIC Educational Resources Information Center

Ehrlich, Lisa R.

This paper focuses on item design considerations faced by instructional designers and evaluators when using computer videodisc delivery systems as a means of assessing learner comprehension and competencies. Media characteristics of various interactive computer/videodisc training systems are briefly discussed as well as reasons for using such…

Solar heating and cooling system design and development

NASA Technical Reports Server (NTRS)

1979-01-01

The design and development of marketable solar heating and cooling systems for single family and commercial applications is described. The delivery, installation, and monitoring of the prototype systems are discussed. Seven operational test sites are discussed in terms of system performance. Problems encountered with equipment and installation were usually due to lack of skills required for solar system installation.

Health Reform: A Community Experience Using Design Research as a Guide

PubMed Central

Severson, Mary A.; Wood, Douglas L.; Chastain, Christine N.; Lee, Laura G.; Rees, Adam C.; Agerter, David C.; Holtz, Carol P.; Broers, Joan K.; Savoleinen, Kimberly H.; Spurrier, Barbara R.; LaRusso, Nicholas F.

2011-01-01

Meaningful health reform in the United States must improve the health of the population while lowering costs. In an effort to provide a framework for doing so, the Institute of Health Care Improvement created the triple aim, which encompasses the goals of (1) improving individual health and experience with the health care system, (2) improving population health, and (3) decreasing the rate of per capita health care costs. Current reform efforts have focused on the development of Patient-Centered Medical Homes (an innovative team-based model of care that facilitates a partnership between the patient’s personal physician coordinating care throughout a patient’s lifetime to maximize health outcomes), but these relatively narrow efforts are focused on office practice and payment methods and are not generally oriented toward community needs. We sought to apply design research in assessing a community opportunity to apply the triple aim as a strategy to transform health care delivery. Mixed methodology provides greater insight into the unexpressed health needs of individuals and into the creation of delivery systems more likely to achieve the triple aim. In a small, midwestern town, a mixed methods approach was used to assess community health needs to facilitate design and implementation of care delivery systems. The research findings suggest that health system design concepts should focus on the creation of health, not health care; foster simplicity; create nurturing relationships; eliminate user fear; and contain costs. These observations can be helpful to health care professionals who are developing new methods of care delivery and policymakers and payers contemplating new payment systems to achieve the goals of the triple aim. PMID:21964174

Nanocarriers in ocular drug delivery: an update review.

PubMed

Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani Rai; Vyas, S P

2009-01-01

Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.

Strategies for transporting nanoparticles across the blood-brain barrier.

PubMed

Zhang, Tian-Tian; Li, Wen; Meng, Guanmin; Wang, Pei; Liao, Wenzhen

2016-02-01

The existence of blood-brain barrier (BBB) hampers the effective treatment of central nervous system (CNS) diseases. Almost all macromolecular drugs and more than 98% of small molecule drugs cannot pass the BBB. Therefore, the BBB remains a big challenge for delivery of therapeutics to the central nervous system. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now possible to design delivery systems that could cross the BBB effectively. Because of their advantageous properties, nanoparticles have been widely deployed for brain-targeted delivery. This review paper presents the current understanding of the BBB under physiological and pathological conditions, and summarizes strategies and systems for BBB crossing with a focus on nanoparticle-based drug delivery systems. In summary, with wider applications and broader prospection the treatment of brain targeted therapy, nano-medicines have proved to be more potent, more specific and less toxic than traditional drug therapy.

Importance of dual delivery systems for bone tissue engineering.

PubMed

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

2016-03-10

Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

MULTI-STAGE DELIVERY NANO-PARTICLE SYSTEMS FOR THERAPEUTIC APPLICATIONS

PubMed Central

Serda, Rita E.; Godin, Biana; Blanco, Elvin; Chiappini, Ciro; Ferrari, Mauro

2010-01-01

Background The daunting task for drug molecules to reach pathological lesions has fueled rapid advances in Nanomedicine. The progressive evolution of nanovectors has led to the development of multi-stage delivery systems aimed at overcoming the numerous obstacles encountered by nanovectors on their journey to the target site. Scope of Review This review summarizes major findings with respect to silicon-based drug delivery vectors for cancer therapeutics and imaging. Based on rational design, well established silicon technologies have been adapted for the fabrication of nanovectors with specific shapes, sizes, and porosities. These vectors are part of a multi-stage delivery system that contains multiple nano-components, each designed to achieve a specific task with the common goal of site-directed delivery of therapeutics. Major Conclusions Quasi-hemispherical and discoidal silicon microparticles are superior to spherical particles with respect to margination in the blood, with particles of different shapes and sizes having unique distributions in vivo. Cellular adhesion and internalization of silicon microparticles is influenced by microparticle shape and surface charge, with the latter dictating binding of serum opsonins. Based on in vitro cell studies, the internalization of porous silicon microparticles by endothelial cells and macrophages is compatible with cellular morphology, intracellular trafficking, mitosis, cell cycle progression, cytokine release, and cell viability. In vivo studies support superior therapeutic efficacy of liposomal encapsulated siRNA when delivered in multi-stage systems compared to free nanoparticles. PMID:20493927

Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers.

PubMed

Chen, Wei; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

2014-09-28

Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention (EPR) effect, and degradation in vivo into nontoxic products after completing their tasks. The current biodegradable drug and gene delivery systems exhibit, however, typically low in vivo therapeutic efficacy, due to issues of low loading capacity, inadequate in vivo stability, premature cargo release, poor uptake by target cells, and slow release of therapeutics inside tumor cells. To overcome these problems, a variety of advanced drug and gene delivery systems has recently been designed and developed based on functional biodegradable polycarbonates and copolymers. Notably, polycarbonates and copolymers with diverse functionalities such as hydroxyl, carboxyl, amine, alkene, alkyne, halogen, azido, acryloyl, vinyl sulfone, pyridyldisulfide, and saccharide, could be readily obtained by controlled ring-opening polymerization. In this paper, we give an overview on design concepts and recent developments of functional polycarbonate-based nanocarriers including stimuli-sensitive, photo-crosslinkable, or active targeting polymeric micelles, polymersomes and polyplexes for enhanced drug and gene delivery in vitro and in vivo. These multifunctional biodegradable nanosystems might be eventually developed for safe and efficient cancer chemotherapy and gene therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Otic drug delivery systems: formulation principles and recent developments.

PubMed

Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng

2018-04-25

Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.

A model of awareness to enhance our understanding of interprofessional collaborative care delivery and health information system design to support it.

PubMed

Kuziemsky, Craig E; Varpio, Lara

2011-08-01

As more healthcare delivery is provided by collaborative teams there is a need for enhanced design of health information systems (HISs) to support collaborative care delivery. The purpose of this study was to develop a model of the different types of awareness that exist in interprofessional collaborative care (ICC) delivery to inform HIS design to support ICC. Qualitative data collection and analysis was done. The data sources consisted of 90 h of non-participant observations and 30 interviews with nurses, physicians, medical residents, volunteers, and personal support workers. Many of the macro-level ICC activities (e.g. morning rounds, shift change) were constituted by micro-level activities that involved different types of awareness. We identified four primary types of ICC awareness: patient, team member, decision making, and environment. Each type of awareness is discussed and supported by study data. We also discuss implication of our findings for enhanced design of existing HISs as well as providing insight on how HISs could be better designed to support ICC awareness. Awareness is a complex yet crucial piece of successful ICC. The information sources that provided and supported ICC awareness were varied. The different types of awareness from the model can help us understand the explicit details of how care providers communicate and exchange information with one another. Increased understanding of ICC awareness can assist with the design and evaluation of HISs to support collaborative activities. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2017-10-13

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

Managerial process improvement: a lean approach to eliminating medication delivery.

PubMed

Hussain, Aftab; Stewart, LaShonda M; Rivers, Patrick A; Munchus, George

2015-01-01

Statistical evidence shows that medication errors are a major cause of injuries that concerns all health care oganizations. Despite all the efforts to improve the quality of care, the lack of understanding and inability of management to design a robust system that will strategically target those factors is a major cause of distress. The paper aims to discuss these issues. Achieving optimum organizational performance requires two key variables; work process factors and human performance factors. The approach is that healthcare administrators must take in account both variables in designing a strategy to reduce medication errors. However, strategies that will combat such phenomena require that managers and administrators understand the key factors that are causing medication delivery errors. The authors recommend that healthcare organizations implement the Toyota Production System (TPS) combined with human performance improvement (HPI) methodologies to eliminate medication delivery errors in hospitals. Despite all the efforts to improve the quality of care, there continues to be a lack of understanding and the ability of management to design a robust system that will strategically target those factors associated with medication errors. This paper proposes a solution to an ambiguous workflow process using the TPS combined with the HPI system.

22 CFR 129.7 - Prior approval (license).

Code of Federal Regulations, 2010 CFR

2010-04-01

...; (ii) Nuclear weapons strategic delivery systems and all components, parts, accessories, attachments specifically designed for such systems and associated equipment; (iii) Nuclear weapons design and test equipment of a nature described by Category XVI of Part 121; (iv) Naval nuclear propulsion equipment of a...

22 CFR 129.7 - Prior approval (license).

Code of Federal Regulations, 2011 CFR

2011-04-01

...; (ii) Nuclear weapons strategic delivery systems and all components, parts, accessories, attachments specifically designed for such systems and associated equipment; (iii) Nuclear weapons design and test equipment of a nature described by Category XVI of part 121; (iv) Naval nuclear propulsion equipment of a...

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment

PubMed Central

Chen, Binlong; Dai, Wenbing; He, Bing; Zhang, Hua; Wang, Xueqing; Wang, Yiguang; Zhang, Qiang

2017-01-01

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects. PMID:28255348

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment.

PubMed

Chen, Binlong; Dai, Wenbing; He, Bing; Zhang, Hua; Wang, Xueqing; Wang, Yiguang; Zhang, Qiang

2017-01-01

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects.

Preliminary design package for prototype solar heating system

NASA Technical Reports Server (NTRS)

1978-01-01

A summary is given of the preliminary analysis and design activity on solar heating systems. The analysis was made without site specific data other than weather; therefore, the results indicate performance expected under these special conditions. Major items include system candidates, design approaches, trade studies and other special data required to evaluate the preliminary analysis and design. The program calls for the development and delivery of eight prototype solar heating and cooling systems for installation and operational test.

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

Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system

NASA Astrophysics Data System (ADS)

Licciardi, Mariano; Scialabba, Cinzia; Giammona, Gaetano; Paolino, Marco; Razzano, Vincenzo; Grisci, Giorgio; Giuliani, Germano; Makovec, Francesco; Cappelli, Andrea

2017-06-01

A tri-component polymer brush (TCPB ), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350 nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin-loaded TCPB nanoparticles (DOXO-TCPB) to be internalized into cancer cells by CD44 receptor mediated uptake was assessed by means of uptake studies in HCT cells. These data were supported by anti-CD44-FITC staining assay. The proposed TCPB nanostructured drug delivery systems have many potential applications in nanomedicine, including cancer targeted drug delivery.

A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine.

PubMed

Jahangirian, Hossein; Lemraski, Ensieh Ghasemian; Webster, Thomas J; Rafiee-Moghaddam, Roshanak; Abdollahi, Yadollah

2017-01-01

This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed "green nanomedicine". Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms) are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow.

Role of pressure-sensitive adhesives in transdermal drug delivery systems.

PubMed

Lobo, Shabbir; Sachdeva, Sameer; Goswami, Tarun

2016-01-01

Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects.

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

PubMed Central

Fonseca-Santos, Bruno; Gremião, Maria Palmira Daflon; Chorilli, Marlus

2015-01-01

Alzheimer’s disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood–brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease. PMID:26345528

ICS-II USA research design and methodology.

PubMed

Rana, H; Andersen, R M; Nakazono, T T; Davidson, P L

1997-05-01

The purpose of the WHO-sponsored International Collaborative Study of Oral Health Outcomes (ICS-II) was to provide policy-markers and researchers with detailed, reliable, and valid data on the oral health situation in their countries or regions, together with comparative data from other dental care delivery systems. ICS-II used a cross-sectional design with no explicit control groups or experimental interventions. A standardized methodology was developed and tested for collecting and analyzing epidemiological, sociocultural, economic, and delivery system data. Respondent information was obtained by household interviews, and clinical examinations were conducted by calibrated oral epidemiologists. Discussed are the sampling design characteristics for the USA research locations, response rates, samples size for interview and oral examination data, weighting procedures, and statistical methods. SUDAAN was used to adjust variance calculations, since complex sampling designs were used.

Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics

PubMed Central

Hong, Seong-Chul; Yoo, Seung-Yup; Kim, Hyeongmin; Lee, Jaehwi

2017-01-01

Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, nanoparticles and thin films. Based on the progress made in chitosan-based drug delivery systems, the usefulness of chitosan has further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessels by which the oxygen and nutrients are supplied. Indeed, it has been reported to be a promising embolic material. For better anti-cancer effect, embolic materials that can locally release anti-cancer drugs were proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. In line with this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents, especially to the site of interest. Thus, in this work, studies where chitosan-based drug delivery systems have successfully been used for local delivery will be presented along with future perspectives. PMID:28257059

Patient and provider perspectives on the design and implementation of an electronic consultation system for kidney care delivery in Canada: a focus group study.

PubMed

Bello, Aminu K; Molzahn, Anita E; Girard, Louis P; Osman, Mohamed A; Okpechi, Ikechi G; Glassford, Jodi; Thompson, Stephanie; Keely, Erin; Liddy, Clare; Manns, Braden; Jinda, Kailash; Klarenbach, Scott; Hemmelgarn, Brenda; Tonelli, Marcello

2017-03-02

We assessed stakeholder perceptions on the use of an electronic consultation system (e-Consult) to improve the delivery of kidney care in Alberta. We aim to identify acceptability, barriers and facilitators to the use of an e-Consult system for ambulatory kidney care delivery. This was a qualitative focus group study using a thematic analysis design. Eight focus groups were held in four locations in the province of Alberta, Canada. In total, there were 72 participants in two broad stakeholder categories: patients (including patients' relatives) and providers (including primary care physicians, nephrologists, other care providers and policymakers). The e-Consult system was generally acceptable across all stakeholder groups. The key barriers identified were length of time required for referring physicians to complete the e-Consult due to lack of integration with current electronic medical records, and concerns that increased numbers of requests might overwhelm nephrologists and lead to a delayed response or an unsustainable system. The key facilitators identified were potential improvement of care coordination, dissemination of best practice through an educational platform, comprehensive data to make decisions without the need for face-to-face consultation, timely feedback to primary care providers, timeliness/reduced delays for patients' rapid triage and identification of cases needing urgent care and improved access to information to facilitate decision-making in patient care. Stakeholder perceptions regarding the e-Consult system were favourable, and the key barriers and facilitators identified will be considered in design and implementation of an acceptable and sustainable electronic consultation system for kidney care delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Submicron Emulsions and Their Applications in Oral Delivery.

PubMed

Mundada, Veenu; Patel, Mitali; Sawant, Krutika

2016-01-01

A "submicron emulsion" is an isotropic mixture of drug, lipids, and surfactants, usually with hydrophilic cosolvents and with droplet diameters ranging from 10 to 500 nm. Submicron emulsions are of increasing interest in medicine due to their kinetic stability, high solubilizing capacity, and tiny globule size. Because of these properties, they have been applied in various fields, such as personal care, cosmetics, health care, pharmaceuticals, and agrochemicals. Submicron emulsions are by far the most advanced nanoparticulate systems for the systemic delivery of biologically active agents for controlled drug delivery and targeting. They are designed mainly for pharmaceutical formulations suitable for various routes of administration like parenteral, ocular, transdermal, and oral. This review article describes the marked potential of submicron emulsions for oral drug delivery owing to their numerous advantages like reduced first pass metabolism, inhibition of P-glycoprotein efflux system, and enhanced absorption via intestinal lymphatic pathway. To overcome the limitations of liquid dosage forms, submicron emulsions can be formulated into solid dosage forms such as solid self-emulsifying systems. This article covers various types of submicron emulsions like microemulsion, nanoemulsion, and self-emulsifying drug delivery system (SEDDS), and their potential pharmaceutical applications in oral delivery with emphasis on their advantages, limitations, and advancements.

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

PubMed

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

2017-12-01

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

AIRTV: Broadband Direct to Aircraft

NASA Astrophysics Data System (ADS)

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

2002-01-01

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

Defining the Content of the Undergraduate Systems Analysis and Design Course as Measured by a Survey of Instructors

ERIC Educational Resources Information Center

Burns, Timothy J.

2011-01-01

There are many factors that make the undergraduate systems analysis and design course somewhat enigmatic in its purpose, and therefore equivocal in its delivery. The purpose of this research is to learn, specifically, what instructors are teaching in their systems analysis and design courses. This paper reports the results of a survey and follow…

Microneedles for enhanced transdermal and intraocular drug delivery.

PubMed

Moffatt, Kurtis; Wang, Yujing; Raj Singh, Thakur Raghu; Donnelly, Ryan F

2017-10-01

Microneedle mediated delivery based research has garnered great interest in recent years. In the past, the initial focus was delivery of macromolecules of biological origin, however the field has now broadened its scope to include transdermal delivery of conventional low molecular weight drug molecules. Great success has been demonstrated utilising this approach, particularly in the field of vaccine delivery. Current technological advances have permitted an enhancement in design formulation, allowing delivery of therapeutic doses of small molecule drugs and biomolecules, aided by larger patch sizes and scalable manufacture. In addition, it has been recently shown that microneedles are beneficial in localisation of drug delivery systems within targeted ocular tissues. Microneedles have the capacity to modify the means in which therapeutics and formulations are delivered to the eye. However, further research is still required due to potential drawbacks and challenges. Indeed, no true microneedle-based transdermal or ocular drug delivery system has yet been marketed. Some concerns have been raised regarding regulatory issues and manufacturing processes of such systems, and those in the field are now actively working to address them. Microneedle-based transdermal and ocular drug delivery systems have the potential to greatly impact not only patient benefits, but also industry, and through diligence, innovation and collaboration, their true potential will begin to be realised within the next 3-5 years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancement of Antiviral Agents Through the Use of Controlled-Release Technology.

DTIC Science & Technology

DL-lactide-co-glycolide) to be used as the polymeric excipients in the microencapsulation work. In addition, we have actively pursued development and testing of poly(I.C) and Je vaccine microcapsule formulations....of this research program are a) To develop a programmed-release delivery system ( microcapsule system) designed to enhance the immunogenic potential of...release microcapsule delivery systems that will enhance the effects of the following immune modulators and antiviral agents: muramyl tripeptide (MTP

Drug Release Kinetics and Transport Mechanisms of Non-degradable and Degradable Polymeric Delivery Systems

PubMed Central

Fu, Yao; Kao, Weiyuan John

2010-01-01

Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. PMID:20331353

Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system.

PubMed

Liu, Quan; Fassihi, Reza

2008-02-04

A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244nm, with automatic sampling over a 24h period using a marketed product as a reference to calculate the "f(2)" factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with "f(2)" of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine.

75 FR 51243 - Trade Mission to the Port of Veracruz

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-19

... collection and management, hazardous materials handling, maritime inspection, operations control, designing... control systems; --Pneumatic delivery systems; --Software for inventory tracking; --Used mobile railcar...

Polymeric drug delivery systems for intraoral site-specific chemoprevention of oral cancer.

PubMed

Desai, Kashappa Goud H

2018-04-01

Oral cancer is among the most prevalent cancers in the world. Moreover, it is one of the major health problems and causes of death in many regions of the world. The traditional treatment modalities include surgical removal, radiation therapy, systemic chemotherapy, or a combination of these methods. In recent decades, there has been significant interest in intraoral site-specific chemoprevention via local drug delivery using polymeric systems. Because of its easy accessibility and clear visibility, the oral mucosa is amenable for local drug delivery. A variety of polymeric systems-such as gels, tablets, films, patches, injectable systems (e.g., millicylindrical implants, microparticles, and in situ-forming depots), and nanosized carriers (e.g., polymeric nanoparticles, nanofibers, polymer-drug conjugates, polymeric micelles, nanoliposomes, nanoemulsions, and polymersomes)-have been developed and evaluated for the local delivery of natural and synthetic chemopreventive agents. The findings of in vitro, ex vivo, and in vivo studies and the positive outcome of clinical trials demonstrate that intraoral site-specific drug delivery is an attractive, highly effective and patient-friendly strategy for the management of oral cancer. Intraoral site-specific drug delivery provides unique therapeutic advantages when compared to systemic chemotherapy. Moreover, intraoral drug delivery systems are self-administrable and can be removed when needed, increasing patient compliance. This article covers important aspects and advances related to the design, development, and efficacy of polymeric systems for intraoral site-specific drug delivery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1383-1413, 2018. © 2017 Wiley Periodicals, Inc.

The development of low-molecular weight hydrogels for applications in cancer therapy

NASA Astrophysics Data System (ADS)

Tian, Ran; Chen, Jin; Niu, Runfang

2014-03-01

To improve the anti-cancer efficacy and to counteract the side effects of chemotherapy, a variety of drug delivery systems have been invented in past decades, but few of these systems have succeeded in clinical trials due to their respective inherent shortcomings. Recently, low-molecular weight hydrogels of peptides that self-assemble via non-covalent interactions have attracted considerable attention due to their good biocompatibility, low toxicity, inherent biodegradability as well as their convenience of design. Low-molecular weight hydrogels have already shown promise in biomedical applications as diverse as 3D-cell culture, enzyme immobilization, controllable MSC differentiation, wound healing, drug delivery etc. Here we review the recent development in the use of low-molecular weight hydrogels for cancer therapy, which may be helpful in the design of soft materials for drug delivery.

Client Functional Assessment Data as Management Information: Woodrow Wilson Rehabilitation Center's Management Information System

PubMed Central

Steidle, Ernest F.

1983-01-01

This paper describes the design of a functional assessment system, a component of a management information system (MIS) that supports a comprehensive rehabilitation facility. Products of the subsystem document the functional status of rehabilitation clients through process evaluation reporting and outcomes reporting. The purpose of this paper is to describe the design of this MIS component. The environment supported, the integration requirements and the needed development approach is unique, requiring significant input from health care professionals, medical informatics specialists, statisticians and program evaluators. Strategies for the implementation of the functional assessment system are the major results reported in this paper. They are most useful to the systems designer or management engineer in a human service delivery setting. MIS plan development, computer file structure and access methods, and approaches to scheduling applications is described. Finally, the development of functional status measures is discussed. Application of the methodologies described will facilitate similar efforts towards systems development in other human service delivery settings.

Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

PubMed

Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

2016-05-01

Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Buparvaquone Nanostructured Lipid Carrier: Development of an Affordable Delivery System for the Treatment of Leishmaniases.

PubMed

Monteiro, Lis Marie; Löbenberg, Raimar; Cotrim, Paulo Cesar; Barros de Araujo, Gabriel Lima; Bou-Chacra, Nádia

2017-01-01

Buparvaquone (BPQ), a veterinary drug, was formulated as nanostructured lipid carriers (NLC) for leishmaniases treatment. The formulation design addressed poor water solubility of BPQ and lack of human drug delivery system. The DSC/TG and microscopy methods were used for solid lipids screening. Softisan® 154 showed highest BPQ solubility in both methods. The BPQ solubility in liquid lipids using HPLC revealed Miglyol® 812 as the best option. Response surface methodology (RSM) was used to identify the optimal Softisan154 : Miglyol 812 ratios (7 : 10 to 2 : 1) and Kolliphor® P188 and Tween® 80 concentration (>3.0% w/w) aiming for z -average in the range of 100-300 nm for macrophage delivery. The NLC obtained by high-pressure homogenization showed low z -averages (<350 nm), polydispersity (<0.3), and encapsulation efficiency close to 100%. DSC/TG and microscopy in combination proved to be a powerful tool to select the solid lipid. The relationship among the variables, demonstrated by a linear mathematical model using RSM, allowed generating a design space. This design space showed the limits in which changes in the variables influenced the z -average. Therefore, these drug delivery systems have the potential to improve the availability of affordable medicines due to the low cost of raw materials, using well established, reliable, and feasible scale-up technology.

Smart roadside initiative : system design document.

DOT National Transportation Integrated Search

2015-09-01

This document describes the software design for the Smart Roadside Initiative (SRI) for the delivery of capabilities related to wireless roadside inspections, electronic screening/virtual weigh stations, universal electronic commercial vehicle identi...

Personalizing knowledge delivery services: a conceptual framework

NASA Technical Reports Server (NTRS)

Majchrzak, Ann; Chelleppa, Ramnath K.; Cooper, Lynne P.; Hars, Alexander

2003-01-01

Consistent with the call of the Minnesota Symposium for new theory in knowledge management, we offer a new conceptualization of Knowledge Management Systems (KMS) as a portfolio of personalized knowledge delivery services. Borrowing from research on online consumer behavior, we describe the challenges imposed by personalized knowledge delivery services, and suggest design parameters that can help to overcome these challenges. We develop our design constructs through a set of hypotheses and discuss the research implications of our new conceptualization. Finally, we describe practical implications suggested by our conceptualization - practical suggestions that we hope to gain some experience with as part of an ongoing action research project at our partner organization.

Additive Construction with Mobile Emplacement (ACME) / Automated Construction of Expeditionary Structures (ACES) Materials Delivery System (MDS)

NASA Technical Reports Server (NTRS)

Mueller, R. P.; Townsend, I. I.; Tamasy, G. J.; Evers, C. J.; Sibille, L. J.; Edmunson, J. E.; Fiske, M. R.; Fikes, J. C.; Case, M.

2018-01-01

The purpose of the Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) project is to incorporate the Liquid Goods Delivery System (LGDS) into the Dry Goods Delivery System (DGDS) structure to create an integrated and automated Materials Delivery System (MDS) for 3D printing structures with ordinary Portland cement (OPC) concrete. ACES 3 is a prototype for 3-D printing barracks for soldiers in forward bases, here on Earth. The LGDS supports ACES 3 by storing liquid materials, mixing recipe batches of liquid materials, and working with the Dry Goods Feed System (DGFS) previously developed for ACES 2, combining the materials that are eventually extruded out of the print nozzle. Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) is a project led by the US Army Corps of Engineers (USACE) and supported by NASA. The equivalent 3D printing system for construction in space is designated Additive Construction with Mobile Emplacement (ACME) by NASA.

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

PubMed Central

Youan, Bi-Botti C.

2010-01-01

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

Patients' perspective of the design of provider-patients electronic communication services.

PubMed

Silhavy, Petr; Silhavy, Radek; Prokopova, Zdenka

2014-06-12

Information Delivery is one the most important tasks in healthcare practice. This article discusses patient's tasks and perspectives, which are then used to design a new Effective Electronic Methodology. The system design methods applicable to electronic communication in the healthcare sector are also described. The architecture and the methodology for the healthcare service portal are set out in the proposed system design.

HESTIA Commodities Exchange Pallet and Sounding Rocket Test Stand

NASA Technical Reports Server (NTRS)

Chaparro, Javier

2013-01-01

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

A novel open-source drug-delivery system that allows for first-of-kind simulation of nonadherence to pharmacological interventions in animal disease models.

PubMed

Thomson, Kyle E; White, H Steve

2014-12-30

Nonadherence to a physician-prescribed therapeutic intervention is a costly, dangerous, and sometimes fatal concern in healthcare. To date, the study of nonadherence has been constrained to clinical studies. The novel approach described herein allows for the preclinical study of nonadherence in etiologically relevant disease animal model systems. The method herein describes a novel computer-automated pellet delivery system which allows for the study of nonadherence in animals. This system described herein allows for tight experimenter control of treatment using a drug-in-food protocol. Food-restricted animals receive either medicated or unmedicated pellets, designed to mimic either "taking" or "missing" a drug. The system described permits the distribution of medicated or unmedicated food pellets on an experimenter-defined feeding schedule. The flexibility of this system permits the delivery of drug according to the known pharmacokinetics of investigational drugs. Current clinical adherence research relies on medication-event monitoring system (MEMS) tracking caps, which allows clinicians to directly monitor patient adherence. However, correlating the effects of nonadherence to efficacy still relies on the accuracy of patient journals. This system allows for the design of studies to address the impact of nonadherence in an etiologically relevant animal model. Given methodological and ethical concerns of designing clinical studies of nonadherence, animal studies are critical to better understand medication adherence. While the system described was designed to measure the impact of nonadherence on seizure control, it is clear that the utility of this system extends beyond epilepsy to include other disease states. Copyright © 2014 Elsevier B.V. All rights reserved.

An overview of Ball Aerospace cryogen storage and delivery systems

NASA Astrophysics Data System (ADS)

Marquardt, J.; Keller, J.; Mills, G.; Schmidt, J.

2015-12-01

Starting on the Gemini program in the 1960s, Beech Aircraft (now Ball Aerospace) has been designing and manufacturing dewars for a variety of cryogens including liquid hydrogen and oxygen. These dewars flew on the Apollo, Skylab and Space Shuttle spacecraft providing fuel cell reactants resulting in over 150 manned spaceflights. Since Space Shuttle, Ball has also built the liquid hydrogen fuel tanks for the Boeing Phantom Eye unmanned aerial vehicle. Returning back to its fuel cell days, Ball has designed, built and tested a volume-constrained liquid hydrogen and oxygen tank system for reactant delivery to fuel cells on unmanned undersea vehicles (UUVs). Herein past history of Ball technology is described. Testing has been completed on the UUV specific design, which will be described.

Recommendations for Benchmarking Preclinical Studies of Nanomedicines.

PubMed

Dawidczyk, Charlene M; Russell, Luisa M; Searson, Peter C

2015-10-01

Nanoparticle-based delivery systems provide new opportunities to overcome the limitations associated with traditional small-molecule drug therapy for cancer and to achieve both therapeutic and diagnostic functions in the same platform. Preclinical trials are generally designed to assess therapeutic potential and not to optimize the design of the delivery platform. Consequently, progress in developing design rules for cancer nanomedicines has been slow, hindering progress in the field. Despite the large number of preclinical trials, several factors restrict comparison and benchmarking of different platforms, including variability in experimental design, reporting of results, and the lack of quantitative data. To solve this problem, we review the variables involved in the design of preclinical trials and propose a protocol for benchmarking that we recommend be included in in vivo preclinical studies of drug-delivery platforms for cancer therapy. This strategy will contribute to building the scientific knowledge base that enables development of design rules and accelerates the translation of new technologies. ©2015 American Association for Cancer Research.

Perspective: Recommendations for benchmarking pre-clinical studies of nanomedicines

PubMed Central

Dawidczyk, Charlene M.; Russell, Luisa M.; Searson, Peter C.

2015-01-01

Nanoparticle-based delivery systems provide new opportunities to overcome the limitations associated with traditional small molecule drug therapy for cancer, and to achieve both therapeutic and diagnostic functions in the same platform. Pre-clinical trials are generally designed to assess therapeutic potential and not to optimize the design of the delivery platform. Consequently, progress in developing design rules for cancer nanomedicines has been slow, hindering progress in the field. Despite the large number of pre-clinical trials, several factors restrict comparison and benchmarking of different platforms, including variability in experimental design, reporting of results, and the lack of quantitative data. To solve this problem, we review the variables involved in the design of pre-clinical trials and propose a protocol for benchmarking that we recommend be included in in vivo pre-clinical studies of drug delivery platforms for cancer therapy. This strategy will contribute to building the scientific knowledge base that enables development of design rules and accelerates the translation of new technologies. PMID:26249177

Models and Procedures for Evaluating Government Provided Leisure Services.

ERIC Educational Resources Information Center

McLean, Christine

1978-01-01

The government attempted to set up a viable management information and feedback system for evaluating accountability in services delivery. Conceptual models for agency goals and services delivery were designed and measures were developed in the provision of leisure and recreational services. Two citizen surveys are described. (Author/CTM)

20 CFR 655.4 - Definitions of terms used in this subpart.

Code of Federal Regulations, 2011 CFR

2011-04-01

... functions. Certifying Officer (CO) means the OFLC official designated by the Administrator, OFLC with making...-Peyser Act to administer public labor exchange delivered through the State's one-stop delivery system in... by means normally assuring next-day delivery, and will end on the day that the employer sends...

Liposomes and nanotechnology in drug development: focus on ocular targets

PubMed Central

Honda, Miki; Asai, Tomohiro; Oku, Naoto; Araki, Yoshihiko; Tanaka, Minoru; Ebihara, Nobuyuki

2013-01-01

Poor drug delivery to lesions in patients’ eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood–retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases. PMID:23439842

Engineering liposomal nanoparticles for targeted gene therapy.

PubMed

Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

2017-08-01

Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

Recent advances in inorganic nanoparticle-based drug delivery systems.

PubMed

Murakami, Tatsuya; Tsuchida, Kunihiro

2008-02-01

Drug delivery systems, designed to enhance drug efficacy and reduce their adverse effects, have evolved accompanied by the development of novel materials. Nanotechnology is an emerging scientific area that has created a variety of intriguing inorganic nanoparticles. In this review, we focus on the feasibility of inorganic nanoparticles, including iron oxide nanoparticles, gold nanoparticles, fullerenes and carbon nanohorns, as drug carriers, and summarize recent advances in this field.

Laser beam delivery at ELI-NP

DOE PAGES

Ursescu, Daniel; Cheriaux, G.; Audebert, P.; ...

2017-01-01

The Laser Beam Delivery (LBD) system technical design report covers the interface between the High Power Laser System (HPLS) and the experiments, together with the pulse quality management. Here, the laser transport part of the LBD has a number of subsystems as follows: the beam transport lines for the six main outputs of HPLS, the additional short and long pulses and the synchronization system including the timing of the laser pulses with the Gamma Beam System (GBS) and the experiments on femtosecond timescale. Pulse quality management, discussed further here, consist in the generation and delivery of multiple HPLS pulses, coherentmore » combining of the HPLS arms, laser pulse diagnostics on target, laser beam dumps, shutters and output energy adaption.« less

Systems modelling approaches to the design of safe healthcare delivery: ease of use and usefulness perceived by healthcare workers.

PubMed

Jun, Gyuchan Thomas; Ward, James; Clarkson, P John

2010-07-01

The UK health service, which had been diagnosed to be seriously out of step with good design practice, has been recommended to obtain knowledge of design and risk management practice from other safety-critical industries. While these other industries have benefited from a broad range of systems modelling approaches, healthcare remains a long way behind. In order to investigate the healthcare-specific applicability of systems modelling approaches, this study identified 10 distinct methods through meta-model analysis. Healthcare workers' perception on 'ease of use' and 'usefulness' was then evaluated. The characterisation of the systems modelling methods showed that each method had particular capabilities to describe specific aspects of a complex system. However, the healthcare workers found that some of the methods, although potentially very useful, would be difficult to understand, particularly without prior experience. This study provides valuable insights into a better use of the systems modelling methods in healthcare. STATEMENT OF RELEVANCE: The findings in this study provide insights into how to make a better use of various systems modelling approaches to the design and risk management of healthcare delivery systems, which have been a growing research interest among ergonomists and human factor professionals.

Children and the Patient Protection and Affordable Care Act: opportunities and challenges in an evolving system.

PubMed

Keller, David; Chamberlain, Lisa J

2014-01-01

The Patient Protection and Affordable Care Act (ACA), passed in 2010, focused primarily on the problems of adults, but the changes in payment for and delivery of care it fosters will likely impact the health care of children. The evolving epidemiology of pediatric illness in the United States has resulted in a relatively small population of medically fragile children dispersed through the country and a large population of children with developmental and behavioral health issues who experience wide degrees of health disparities. Review of previous efforts to change the health care system reveals specific innovations in child health delivery that have been designed to address issues of child health. The ACA is complex and contains some language that improves access to care, quality of care, and the particular needs of the pediatric workforce. Most of the payment models and delivery systems proposed in the ACA, however, were not designed with the needs of children in mind and will need to be adapted to address their needs. To assure that the needs of children are met as systems evolve, child health professionals within and outside academe will need to focus their efforts in clinical care, research, education, and advocacy to incorporate child health programs into changing systems and to prevent unintended harm to systems designed to care for children. Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine

PubMed Central

Jahangirian, Hossein; Lemraski, Ensieh Ghasemian; Webster, Thomas J; Rafiee-Moghaddam, Roshanak; Abdollahi, Yadollah

2017-01-01

This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed “green nanomedicine”. Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms) are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow. PMID:28442906

Designing the modern pump: engineering aspects of continuous subcutaneous insulin infusion software.

PubMed

Welsh, John B; Vargas, Steven; Williams, Gary; Moberg, Sheldon

2010-06-01

Insulin delivery systems attracted the efforts of biological, mechanical, electrical, and software engineers well before they were commercially viable. The introduction of the first commercial insulin pump in 1983 represents an enduring milestone in the history of diabetes management. Since then, pumps have become much more than motorized syringes and have assumed a central role in diabetes management by housing data on insulin delivery and glucose readings, assisting in bolus estimation, and interfacing smoothly with humans and compatible devices. Ensuring the integrity of the embedded software that controls these devices is critical to patient safety and regulatory compliance. As pumps and related devices evolve, software engineers will face challenges and opportunities in designing pumps that are safe, reliable, and feature-rich. The pumps and related systems must also satisfy end users, healthcare providers, and regulatory authorities. In particular, pumps that are combined with glucose sensors and appropriate algorithms will provide the basis for increasingly safe and precise automated insulin delivery-essential steps to developing a fully closed-loop system.

An investigation into the placement of force delivery systems and the initial forces applied by clinicians during space closure.

PubMed

Nattrass, C; Ireland, A J; Sherriff, M

1997-05-01

This in vitro investigation was designed to establish not only how clinicians apply forces for space closure when using the straight wire appliance and sliding mechanics, but also to quantify the initial force levels produced. A single typodont, with residual extraction space in each quadrant, was set up to simulate space closure using sliding mechanics. On two occasions, at least 2 months apart, 18 clinicians were asked to apply three force delivery systems to the typodont, in the manner in which they would apply it in a clinical situation. The three types of force delivery system investigated were elastomeric chain, an elastomeric module on a steel ligature, and a nickel-titanium closed coil spring. A choice of spaced or unspaced elastomeric chain produced by a single manufacturer was provided. The amount of stretch which was placed on each type of system was measured and, using an Instron Universal Testing Machine, the initial force which would be generated by each force delivery system was established. Clinicians were assessed to examine their consistency in the amount of stretch which each placed on the force delivery systems, their initial force application and their ability to apply equivalent forces with the different types of force delivery system. The clinicians were found to be consistent in their method of application of the force delivery systems and, therefore, their force application, as individuals, but there was a wide range of forces applied as a group. However, most clinicians applied very different forces when using different force delivery systems. When using the module on a ligature the greatest force was applied, whilst the nickel titanium coil springs provided the least force.

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

PubMed

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

2013-03-01

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

A concise review on smart polymers for controlled drug release.

PubMed

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

2016-06-01

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

MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

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

Yang, D; Li, X; Li, H

2014-06-15

Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beammore » segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly chart review.« less

A software tool to automatically assure and report daily treatment deliveries by a cobalt‐60 radiation therapy device

PubMed Central

Wooten, H. Omar; Green, Olga; Li, Harold H.; Liu, Shi; Li, Xiaoling; Rodriguez, Vivian; Mutic, Sasa; Kashani, Rojano

2016-01-01

The aims of this study were to develop a method for automatic and immediate verification of treatment delivery after each treatment fraction in order to detect and correct errors, and to develop a comprehensive daily report which includes delivery verification results, daily image‐guided radiation therapy (IGRT) review, and information for weekly physics reviews. After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a commercial MRI‐guided radiotherapy treatment machine, we designed a procedure to use 1) treatment plan files, 2) delivery log files, and 3) beam output information to verify the accuracy and completeness of each daily treatment delivery. The procedure verifies the correctness of delivered treatment plan parameters including beams, beam segments and, for each segment, the beam‐on time and MLC leaf positions. For each beam, composite primary fluence maps are calculated from the MLC leaf positions and segment beam‐on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. A daily treatment delivery report is designed to include all required information for IGRT and weekly physics reviews including the plan and treatment fraction information, daily beam output information, and the treatment delivery verification results. A computer program was developed to implement the proposed procedure of the automatic delivery verification and daily report generation for an MRI guided radiation therapy system. The program was clinically commissioned. Sensitivity was measured with simulated errors. The final version has been integrated into the commercial version of the treatment delivery system. The method automatically verifies the EBRT treatment deliveries and generates the daily treatment reports. Already in clinical use for over one year, it is useful to facilitate delivery error detection, and to expedite physician daily IGRT review and physicist weekly chart review. PACS number(s): 87.55.km PMID:27167269

The ALL-OUT Library; A Design for Computer-Powered, Multidimensional Services.

ERIC Educational Resources Information Center

Sleeth, Jim; LaRue, James

1983-01-01

Preliminary description of design of electronic library and home information delivery system highlights potentials of personal computer interface program (applying for service, assuring that users are valid, checking for measures, searching, locating titles) and incorporation of concepts used in other information systems (security checks,…

A light-weight compact proton gantry design with a novel dose delivery system for broad-energetic laser-accelerated beams

NASA Astrophysics Data System (ADS)

Masood, U.; Cowan, T. E.; Enghardt, W.; Hofmann, K. M.; Karsch, L.; Kroll, F.; Schramm, U.; Wilkens, J. J.; Pawelke, J.

2017-07-01

Proton beams may provide superior dose-conformity in radiation therapy. However, the large sizes and costs limit the widespread use of proton therapy (PT). The recent progress in proton acceleration via high-power laser systems has made it a compelling alternative to conventional accelerators, as it could potentially reduce the overall size and cost of the PT facilities. However, the laser-accelerated beams exhibit different characteristics than conventionally accelerated beams, i.e. very intense proton bunches with large divergences and broad-energy spectra. For the application of laser-driven beams in PT, new solutions for beam transport, such as beam capture, integrated energy selection, beam shaping and delivery systems are required due to the specific beam parameters. The generation of these beams are limited by the low repetition rate of high-power lasers and this limitation would require alternative solutions for tumour irradiation which can efficiently utilize the available high proton fluence and broad-energy spectra per proton bunch to keep treatment times short. This demands new dose delivery system and irradiation field formation schemes. In this paper, we present a multi-functional light-weight and compact proton gantry design for laser-driven sources based on iron-less pulsed high-field magnets. This achromatic design includes improved beam capturing and energy selection systems, with a novel beam shaping and dose delivery system, so-called ELPIS. ELPIS system utilizes magnetic fields, instead of physical scatterers, for broadening the spot-size of broad-energetic beams while capable of simultaneously scanning them in lateral directions. To investigate the clinical feasibility of this gantry design, we conducted a treatment planning study with a 3D treatment planning system augmented for the pulsed beams with optimizable broad-energetic widths and selectable beam spot sizes. High quality treatment plans could be achieved with such unconventional beam parameters, deliverable via the presented gantry and ELPIS dose delivery system. The conventional PT gantries are huge and require large space for the gantry to rotate the beam around the patient, which could be reduced up to 4 times with the presented pulse powered gantry system. The further developments in the next generation petawatt laser systems and laser-targets are crucial to reach higher proton energies. However, if proton energies required for therapy applications are reached it could be possible in future to reduce the footprint of the PT facilities, without compromising on clinical standards.

A light-weight compact proton gantry design with a novel dose delivery system for broad-energetic laser-accelerated beams.

PubMed

Masood, U; Cowan, T E; Enghardt, W; Hofmann, K M; Karsch, L; Kroll, F; Schramm, U; Wilkens, J J; Pawelke, J

2017-07-07

Proton beams may provide superior dose-conformity in radiation therapy. However, the large sizes and costs limit the widespread use of proton therapy (PT). The recent progress in proton acceleration via high-power laser systems has made it a compelling alternative to conventional accelerators, as it could potentially reduce the overall size and cost of the PT facilities. However, the laser-accelerated beams exhibit different characteristics than conventionally accelerated beams, i.e. very intense proton bunches with large divergences and broad-energy spectra. For the application of laser-driven beams in PT, new solutions for beam transport, such as beam capture, integrated energy selection, beam shaping and delivery systems are required due to the specific beam parameters. The generation of these beams are limited by the low repetition rate of high-power lasers and this limitation would require alternative solutions for tumour irradiation which can efficiently utilize the available high proton fluence and broad-energy spectra per proton bunch to keep treatment times short. This demands new dose delivery system and irradiation field formation schemes. In this paper, we present a multi-functional light-weight and compact proton gantry design for laser-driven sources based on iron-less pulsed high-field magnets. This achromatic design includes improved beam capturing and energy selection systems, with a novel beam shaping and dose delivery system, so-called ELPIS. ELPIS system utilizes magnetic fields, instead of physical scatterers, for broadening the spot-size of broad-energetic beams while capable of simultaneously scanning them in lateral directions. To investigate the clinical feasibility of this gantry design, we conducted a treatment planning study with a 3D treatment planning system augmented for the pulsed beams with optimizable broad-energetic widths and selectable beam spot sizes. High quality treatment plans could be achieved with such unconventional beam parameters, deliverable via the presented gantry and ELPIS dose delivery system. The conventional PT gantries are huge and require large space for the gantry to rotate the beam around the patient, which could be reduced up to 4 times with the presented pulse powered gantry system. The further developments in the next generation petawatt laser systems and laser-targets are crucial to reach higher proton energies. However, if proton energies required for therapy applications are reached it could be possible in future to reduce the footprint of the PT facilities, without compromising on clinical standards.

A community-based event delivery protocol in publish/subscribe systems for delay tolerant sensor networks.

PubMed

Liu, Nianbo; Liu, Ming; Zhu, Jinqi; Gong, Haigang

2009-01-01

The basic operation of a Delay Tolerant Sensor Network (DTSN) is to finish pervasive data gathering in networks with intermittent connectivity, while the publish/subscribe (Pub/Sub for short) paradigm is used to deliver events from a source to interested clients in an asynchronous way. Recently, extension of Pub/Sub systems in DTSNs has become a promising research topic. However, due to the unique frequent partitioning characteristic of DTSNs, extension of a Pub/Sub system in a DTSN is a considerably difficult and challenging problem, and there are no good solutions to this problem in published works. To ad apt Pub/Sub systems to DTSNs, we propose CED, a community-based event delivery protocol. In our design, event delivery is based on several unchanged communities, which are formed by sensor nodes in the network according to their connectivity. CED consists of two components: event delivery and queue management. In event delivery, events in a community are delivered to mobile subscribers once a subscriber comes into the community, for improving the data delivery ratio. The queue management employs both the event successful delivery time and the event survival time to decide whether an event should be delivered or dropped for minimizing the transmission overhead. The effectiveness of CED is demonstrated through comprehensive simulation studies.

Nanoparticle-mediated growth factor delivery systems: A new way to treat Alzheimer's disease.

PubMed

Lauzon, Marc-Antoine; Daviau, Alex; Marcos, Bernard; Faucheux, Nathalie

2015-05-28

The number of people diagnosed with Alzheimer's disease (AD) is increasing steadily as the world population ages, thus creating a huge socio-economic burden. Current treatments have only transient effects and concentrate on a single aspect of AD. There is much evidence suggesting that growth factors (GFs) have a great therapeutic potential and can play on all AD hallmarks. Because GFs are prone to denaturation and clearance, a delivery system is required to ensure protection and a sustainable delivery. This review provides information about the latest advances in the development of GF delivery systems (GFDS) targeting the brain in terms of in vitro and in vivo effects in the context of AD and discusses new strategies designed to increase the availability and the specificity of GFs to the brain. This paper also discusses, on a mechanistic level, the different delivery hurdles encountered by the carrier or the GF itself from its injection site up to the brain tissue. The major mass transport phenomena influencing the delivery systems targeting the brain are addressed and insights are given about how mechanistic mathematical frameworks can be developed to use and optimize them. Copyright © 2015. Published by Elsevier B.V.

Solid Footing.

ERIC Educational Resources Information Center

Franzen, Mark; Gorrell, Kyle

2002-01-01

Based on one school district's experience, discusses raised access flooring systems for schools. Addresses the nuts and bolts of such flooring systems, integrating an air delivery system below the flooring, advantages of floor-level air supply, and design issues. (EV)

Integrated care management: aligning medical call centers and nurse triage services.

PubMed

Kastens, J M

1998-01-01

Successful integrated delivery systems must aggressively design new approaches to managing patient care. Implementing a comprehensive care management model to coordinate patient care across the continuum is essential to improving patient care and reducing costs. The practice of telephone nursing and the need for experienced registered nurses to staff medical call centers, nurse triage centers, and outbound telemanagement is expanding as the penetration of full-risk capitated managed care contracts are signed. As health systems design their new care delivery approaches and care management models, medical call centers will be an integral approach to managing demand for services, chronic illnesses, and prevention strategies.

Aerobrake concepts for NTP systems study

NASA Technical Reports Server (NTRS)

Cruz, Manuel I.

1992-01-01

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

Design of a Rich-Prospect Browsing Interface for Seniors: A Qualitative Study of Image Similarity Clustering

ERIC Educational Resources Information Center

Ruecker, Stan; Given, Lisa M.; Sadler, Elizabeth; Ruskin, Andrea; Simpson, Heather

2007-01-01

This paper examines inclusive design delivery through interface design, with a particular focus on access to healthcare resources for seniors. The goal of the project was to examine how seniors are able to access drug information using two different online systems. In the existing retrieval system, pills are identified using a standard search…

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

PubMed

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

1991-06-01

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

Bioresorbable polyelectrolytes for smuggling drugs into cells.

PubMed

Jaganathan, Sripriya

2016-06-01

There is ample evidence that biodegradable polyelectrolyte nanocapsules are multifunctional vehicles which can smuggle drugs into cells, and release them upon endogenous activation. A large number of endogenous stimuli have already been tested in vitro, and in vivo research is escalating. Thus, the interest in the design of intelligent polyelectrolyte multilayer (PEM) drug delivery systems is clear. The need of the hour is a systematic translation of PEM-based drug delivery systems from the lab to clinical studies. Reviews on multifarious stimuli that can trigger the release of drugs from such systems already exist. This review summarizes the available literature, with emphasis on the recent progress in PEM-based drug delivery systems that are receptive in the presence of endogenous stimuli, including enzymes, glucose, glutathione, pH, and temperature, and addresses different active and passive drug targeting strategies. Insights into the current knowledge on the diversified endogenous approaches and methodological challenges may bring inspiration to resolve issues that currently bottleneck the successful implementation of polyelectrolytes into the catalog of third-generation drug delivery systems.

Ethosomes and Transfersomes: Principles, Perspectives and Practices.

PubMed

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

2017-01-01

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

Multiscale benchmarking of drug delivery vectors.

PubMed

Summers, Huw D; Ware, Matthew J; Majithia, Ravish; Meissner, Kenith E; Godin, Biana; Rees, Paul

2016-10-01

Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose-response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo. Copyright © 2016 Elsevier Inc. All rights reserved.

Computational and Pharmacological Target of Neurovascular Unit for Drug Design and Delivery

PubMed Central

2015-01-01

The blood-brain barrier (BBB) is a dynamic and highly selective permeable interface between central nervous system (CNS) and periphery that regulates the brain homeostasis. Increasing evidences of neurological disorders and restricted drug delivery process in brain make BBB as special target for further study. At present, neurovascular unit (NVU) is a great interest and highlighted topic of pharmaceutical companies for CNS drug design and delivery approaches. Some recent advancement of pharmacology and computational biology makes it convenient to develop drugs within limited time and affordable cost. In this review, we briefly introduce current understanding of the NVU, including molecular and cellular composition, physiology, and regulatory function. We also discuss the recent technology and interaction of pharmacogenomics and bioinformatics for drug design and step towards personalized medicine. Additionally, we develop gene network due to understand NVU associated transporter proteins interactions that might be effective for understanding aetiology of neurological disorders and new target base protective therapies development and delivery. PMID:26579539

Patients’ Perspective of the Design of Provider-Patients Electronic Communication Services

PubMed Central

Silhavy, Petr; Silhavy, Radek; Prokopova, Zdenka

2014-01-01

Information Delivery is one the most important tasks in healthcare practice. This article discusses patient’s tasks and perspectives, which are then used to design a new Effective Electronic Methodology. The system design methods applicable to electronic communication in the healthcare sector are also described. The architecture and the methodology for the healthcare service portal are set out in the proposed system design. PMID:24927038

Micro-precise spatiotemporal delivery system embedded in 3D printing for complex tissue regeneration.

PubMed

Tarafder, Solaiman; Koch, Alia; Jun, Yena; Chou, Conrad; Awadallah, Mary R; Lee, Chang H

2016-04-25

Three dimensional (3D) printing has emerged as an efficient tool for tissue engineering and regenerative medicine, given its advantages for constructing custom-designed scaffolds with tunable microstructure/physical properties. Here we developed a micro-precise spatiotemporal delivery system embedded in 3D printed scaffolds. PLGA microspheres (μS) were encapsulated with growth factors (GFs) and then embedded inside PCL microfibers that constitute custom-designed 3D scaffolds. Given the substantial difference in the melting points between PLGA and PCL and their low heat conductivity, μS were able to maintain its original structure while protecting GF's bioactivities. Micro-precise spatial control of multiple GFs was achieved by interchanging dispensing cartridges during a single printing process. Spatially controlled delivery of GFs, with a prolonged release, guided formation of multi-tissue interfaces from bone marrow derived mesenchymal stem/progenitor cells (MSCs). To investigate efficacy of the micro-precise delivery system embedded in 3D printed scaffold, temporomandibular joint (TMJ) disc scaffolds were fabricated with micro-precise spatiotemporal delivery of CTGF and TGFβ3, mimicking native-like multiphase fibrocartilage. In vitro, TMJ disc scaffolds spatially embedded with CTGF/TGFβ3-μS resulted in formation of multiphase fibrocartilaginous tissues from MSCs. In vivo, TMJ disc perforation was performed in rabbits, followed by implantation of CTGF/TGFβ3-μS-embedded scaffolds. After 4 wks, CTGF/TGFβ3-μS embedded scaffolds significantly improved healing of the perforated TMJ disc as compared to the degenerated TMJ disc in the control group with scaffold embedded with empty μS. In addition, CTGF/TGFβ3-μS embedded scaffolds significantly prevented arthritic changes on TMJ condyles. In conclusion, our micro-precise spatiotemporal delivery system embedded in 3D printing may serve as an efficient tool to regenerate complex and inhomogeneous tissues.

Designing food delivery systems: challenges related to the in vitro methods employed to determine the fate of bioactives in the gut.

PubMed

Arranz, Elena; Corredig, Milena; Guri, Anilda

2016-08-10

An in depth understanding of the underpinning mechanisms that relate to food disruption and processing in the gastrointestinal tract is necessary to achieve optimal intake of nutrients and their bioefficacy. Although in vivo trials can provide insights on physiological responses of nutrients, in vitro assays are often applied as tools to understand specific mechanisms, or as prescreening methods to determine the factors associated with the uptake of food components in the gastrointestinal tract. In vitro assays are also often utilized to design novel or improved food delivery systems. In this review the available approaches to study delivery and uptake of food bioactives and the associated challenges are discussed. For an in depth understanding of food processing in the gastrointestinal tract, it is necessary to apply multidisciplinary methodologies, at the interface between materials science, chemistry, physics and biology.

Efficient siRNA delivery system using carboxilated single-wall carbon nanotubes in cancer treatment.

PubMed

Neagoe, Ioana Berindan; Braicu, Cornelia; Matea, Cristian; Bele, Constantin; Florin, Graur; Gabriel, Katona; Veronica, Chedea; Irimie, Alexandru

2012-08-01

Several functionalized carbon nanotubes have been designed and tested for the purpose of nucleic acid delivery. In this study, the capacity of SWNTC-COOH for siRNA deliverey were investigated delivery in parallel with an efficient commercial system. Hep2G cells were reverse-transfected with 50 nM siRNA (p53 siRNA, TNF-alphasiRNA, VEGFsiRNA) using the siPORT NeoFX (Ambion) transfection agent in paralel with SWNTC-COOH, functionalised with siRNA. The highest level of gene inhibition was observed in the cases treated with p53 siRNA gene; in the case of transfection with siPort, the NeoFX value was 33.8%, while in the case of SWNTC-COOH as delivery system for p53 siRNA was 37.5%. The gene silencing capacity for VEGF was 53.7%, respectively for TNF-alpha 56.7% for siPORT NeoFX delivery systems versus 47.7% (VEGF) and 46.5% (TNF-alpha) for SWNTC-COOH delivery system. SWNTC-COOH we have been showed to have to be an efficient carrier system. The results from the inhibition of gene expresion for both transfection systems were confirmed at protein level. Overall, the lowest mRNA expression was confirmed at protein level, especially in the case of p53 siRNA and TNF-alpha siRNA transfection. Less efficient reduction protein expressions were observed in the case of VEGF siRNA, for both transfection systems at 24 h; only at 48 h, there was a statistically significant reduction of VEGF protein expression. SWCNT-COOH determined an efficient delivery of siRNA. SWNTC-COOH, combined with suitable tumor markers like p53 siRNA, TNFalpha siRNA or VEGF siRNA can be used for the efficient delivery of siRNA.

Technologies for Controlled, Local Delivery of siRNA

PubMed Central

Sarett, Samantha M.; Nelson, Christopher E.; Duvall, Craig L.

2015-01-01

The discovery of RNAi in the late 1990s unlocked a new realm of therapeutic possibilities by enabling potent and specific silencing of theoretically any desired genetic target. Better elucidation of the mechanism of action, the impact of chemical modifications that stabilize and reduce nonspecific effects of siRNA molecules, and the key design considerations for effective delivery systems has spurred progress toward developing clinically-successful siRNA therapies. A logical aim for initial siRNA translation is local therapies, as delivering siRNA directly to its site of action helps to ensure that a sufficient dose reaches the target tissue, lessens the potential for off-target side effects, and circumvents the substantial systemic delivery barriers. While topical siRNA delivery has progressed into numerous clinical trials, an enormous opportunity also exists to develop sustained-release, local delivery systems that enable both spatial and temporal control of gene silencing. This review focuses on material platforms that establish both localized and controlled gene silencing, with emphasis on the systems that show most promise for clinical translation. PMID:26476177

Public service communications

NASA Technical Reports Server (NTRS)

Whalen, A. A.

1979-01-01

The purpose of the paper is to construct, for detailed analysis, satellite and terrestrial communications delivery system models. Attention is given to the Public Service Communications Delivery System Architectural Study, that takes advantage of the extensive experience which exists among the public service experimenters. The Application Test Pilot is examined, which is a program designed to help awareness, in a practical sense, of the technology available and by the users innovative talents, adapts the technology to solve their problems.

Perceptions of International Students on Service Quality Delivery in a Malaysian Public University

ERIC Educational Resources Information Center

Njie, Baboucarr; Asimiran, Soaib; Baki, Roselan

2012-01-01

Purpose: The purpose of this study is to explore the perceptions of international students of service quality delivery (SQD) in a Malaysian public university. Design/methodology/approach: The study was limited to the University's immediate physical environment and its associated human and systems-based services. The physical environment in this…

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2011 CFR

2011-10-01

... unique identification number and maximum working pressure. (c) Post-delivery hose check. After each... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... actuate all emergency discharge control devices designed to close the internal self-closing stop valve to...

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2014 CFR

2014-10-01

... unique identification number and maximum working pressure. (c) Post-delivery hose check. After each... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... actuate all emergency discharge control devices designed to close the internal self-closing stop valve to...

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2013 CFR

2013-10-01

... unique identification number and maximum working pressure. (c) Post-delivery hose check. After each... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... actuate all emergency discharge control devices designed to close the internal self-closing stop valve to...

49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

Code of Federal Regulations, 2012 CFR

2012-10-01

... unique identification number and maximum working pressure. (c) Post-delivery hose check. After each... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... actuate all emergency discharge control devices designed to close the internal self-closing stop valve to...

The New Philanthropist: Eric Schnell--Ohio State University

ERIC Educational Resources Information Center

Library Journal, 2005

2005-01-01

As head of information technology at the Prior Health Sciences Library, Eric Schnell likes to improve products that don't fully meet his library's purposes. His first major software product, the award-winning Prospero Electronic Delivery Project, is a web-based document delivery system designed to complement Ariel[R] by converting documents to a…

Design, modeling and simulation of MEMS-based silicon Microneedles

NASA Astrophysics Data System (ADS)

Amin, F.; Ahmed, S.

2013-06-01

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

Design of a clinical notification system.

PubMed

Wagner, M M; Tsui, F C; Pike, J; Pike, L

1999-01-01

We describe the requirements and design of an enterprise-wide notification system. From published descriptions of notification schemes, our own experience, and use cases provided by diverse users in our institution, we developed a set of functional requirements. The resulting design supports multiple communication channels, third party mappings (algorithms) from message to recipient and/or channel of delivery, and escalation algorithms. A requirement for multiple message formats is addressed by a document specification. We implemented this system in Java as a CORBA object. This paper describes the design and current implementation of our notification system.

Patient-centredness in integrated healthcare delivery systems - needs, expectations and priorities for organised healthcare systems.

PubMed

Juhnke, Christin; Mühlbacher, Axel C

2013-01-01

Patient-centred healthcare is becoming a more significant success factor in the design of integrated healthcare systems. The objective of this study is to structure a patient-relevant hierarchy of needs and expectations for the design of organised healthcare delivery systems. A questionnaire with 84 items was conducted with N = 254 healthcare experts and N = 670 patients. Factor analyses were performed using SPSS©18. The number of factors retained was controlled by Kaiser's criterion, validation of screeplots and interpretability of the items. Cronbach's α was used to assess the internal consistency of the subscales. Exploratory factor analysis led to 24 factors in the expert sample and 20 in the patient sample. After analysing the screeplots, confirmatory factor analyses were computed for 7-factor solutions accounting for 42.963% of the total variance and Kaiser-Meyer-Olkin of 0.914 for the patients (experts: 38.427%, Kaiser-Meyer-Olkin = 0.797). Cronbach's α ranged between 0.899 and 0.756. Based on the analysis, coordinated care could be differentiated into seven dimensions: access, data and information, service and infrastructure, professional care, interpersonal care, individualised care, continuity and coordination. The study provides insight into patient and experts expectations towards the organisation of integrated healthcare delivery systems. If providers and payers can take into account patient needs and expectations while implementing innovative healthcare delivery systems, greater acceptance and satisfaction will be achieved. In the best case, this will lead to better adherence resulting in better clinical outcomes.

Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery.

PubMed

Garland, Martin J; Caffarel-Salvador, Ester; Migalska, Katarzyna; Woolfson, A David; Donnelly, Ryan F

2012-04-10

It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery, as well as enabling the rate of delivery to be achieved with precise electronic control. However, no reports exist on the combination of ITP with in situ drug loaded polymeric MN delivery systems. Furthermore, although a number of studies have highlighted the importance of MN design for transdermal drug delivery enhancement, to date, there has been no systematic investigation of the influence of MN geometry on the performance of polymeric MN arrays which are designed to remain in contact with the skin during the period of drug delivery. As such, for the first time, this study reports on the effect of MN heigth and MN density upon the transdermal delivery of small hydrophilic compounds (theophylline, methylene blue, and fluorescein sodium) across neonatal porcine skin in vitro, with the optimised MN array design evaluated for its potential in the electrically faciliatated delivery of peptide (bovine insulin) and protein (fluorescein isothiocyanate-labelled bovine serum albumin (FTIC-BSA)) macromolecules. The results of the in vitro drug release investigations revealed that the extent of transdermal delivery was dependent upon the design of the MN array employed, whereby an increase in MN height and an increase in MN density led to an increase in the extent of transdermal drug delivery achieved 6h after MN application. Overall, the in vitro permeation studies revealed that the MN design containing 361 MNs/cm(2) of 600 μm height resulted in the greatest extent of transdermal drug delivery. As such, this design was evaluated for its potential in the MN mediated iontophoretic transdermal delivery. Whilst the combination of MN and ITP did not further enhance the extent of small molecular weight solute delivery, the extent of peptide/protein release was significantly enhanced when ITP was used in combination of the soluble PMVE/MA MN arrays. For example, the cumulative amount of insulin permeated across neonatal porcine skin at 6h was found to be approximately 150 μg (3.25%), 227 μg (4.85%) and 462 μg (9.87%) for ITP, MN, and MN/ITP delivery strategies, respectively. Similarly, the cumulative amount of FTIC-BSA delivered across neonatal porcine skin after a 6h period was found to be approximately 110 μg (4.53%) for MN alone and 326 μg (13.40%) for MN in combination with anodal ITP (p<0.001). As such, drug loaded soluble PMVE/MA MN arrays show promise for the electrically controlled transdermal delivery of biomacromolecules in a simple, one-step approach. Copyright © 2012 Elsevier B.V. All rights reserved.

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part I: Recapitulation of Native Tissue Healing and Variables for the Design of Delivery Systems

PubMed Central

Santo, Vítor E.; Mano, João F.; Reis, Rui L.

2013-01-01

The potential of growth factors to stimulate tissue healing through the enhancement of cell proliferation, migration, and differentiation is undeniable. However, critical parameters on the design of adequate carriers, such as uncontrolled spatiotemporal presence of bioactive factors, inadequate release profiles, and supraphysiological dosages of growth factors, have impaired the translation of these systems onto clinical practice. This review describes the healing cascades for bone, cartilage, and osteochondral interface, highlighting the role of specific growth factors for triggering the reactions leading to tissue regeneration. Critical criteria on the design of carriers for controlled release of bioactive factors are also reported, focusing on the need to provide a spatiotemporal control over the delivery and presentation of these molecules. PMID:23268651

Vocational technical and adult education: Status, trends and issues related to electronic delivery

NASA Technical Reports Server (NTRS)

Rothenberg, D.

1973-01-01

Data are analyzed, and trends and issues are discussed to provide information useful to the systems designer who wishes to identify and assess the opportunities for large scale electronic delivery in vocational/technical and adult education. Issues connected with vocational/technical education are investigated, with emphasis on those issues in the current spotlight which are relevant to the possibilities of electronic delivery. The current role of media is examined in vocational/technical instruction.

Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs.

PubMed

Quinn, Helen L; Bonham, Louise; Hughes, Carmel M; Donnelly, Ryan F

2015-10-01

Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Colloidal microgels in drug delivery applications

PubMed Central

Vinogradov, Serguei V.

2005-01-01

Colloidal microgels have recently received attention as environmentally responsive systems and now are increasingly used in applications as carriers for therapeutic drugs and diagnostic agents. Synthetic microgels consist of a crosslinked polymer network that provides a depot for loaded drugs, protection against environmental hazards and template for post-synthetic modification or vectorization of the drug carriers. The aim of this manuscript is to review recent attempts to develop new microgel formulations for oral drug delivery, to design metal-containing microgels for diagnostic and therapeutic applications, and to advance approaches including the systemic administration of microgels. Novel nanogel drug delivery systems developed in the authors’ laboratory are discussed in details including aspects of their synthesis, vectorization and recent applications for encapsulation of low molecular weight drugs or formulation of biological macromolecules. The findings reviewed here are encouraging for further development of the nanogels as intelligent drug carriers with such features as targeted delivery and triggered drug release. PMID:17168773

Elution characteristics of teicoplanin-loaded biodegradable borate glass/chitosan composite.

PubMed

Jia, Wei-Tao; Zhang, Xin; Zhang, Chang-Qing; Liu, Xin; Huang, Wen-Hai; Rahaman, Mohamed N; Day, Delbert E

2010-03-15

Local antibiotic delivery system has an advantage over systemic antibiotic for osteomyelitis treatment due to the delivery of high local antibiotic concentration while avoiding potential systemic toxicity. Composite biomaterials with multifunctional roles, consisting of a controlled antibiotic release, a mechanical (load-bearing) function, and the ability to promote bone regeneration, gradually become the most active area of investigation and development of local antibiotic delivery vehicles. In the present study, a composite of borate glass and chitosan (designated BG/C) was developed as teicoplanin delivery vehicle. The in vitro elution kinetics and antibacterial activity of teicoplanin released from BG/C composite as a function of immersion time were determined. Moreover, the pH changes of eluents and the bioactivity of the composite were characterized using scanning electron microscopy coupled with energy-dispersive spectroscopy and X-ray diffraction analysis. 2009 Elsevier B.V. All rights reserved.

Buparvaquone Nanostructured Lipid Carrier: Development of an Affordable Delivery System for the Treatment of Leishmaniases

PubMed Central

Löbenberg, Raimar; Cotrim, Paulo Cesar

2017-01-01

Buparvaquone (BPQ), a veterinary drug, was formulated as nanostructured lipid carriers (NLC) for leishmaniases treatment. The formulation design addressed poor water solubility of BPQ and lack of human drug delivery system. The DSC/TG and microscopy methods were used for solid lipids screening. Softisan® 154 showed highest BPQ solubility in both methods. The BPQ solubility in liquid lipids using HPLC revealed Miglyol® 812 as the best option. Response surface methodology (RSM) was used to identify the optimal Softisan154 : Miglyol 812 ratios (7 : 10 to 2 : 1) and Kolliphor® P188 and Tween® 80 concentration (>3.0% w/w) aiming for z-average in the range of 100–300 nm for macrophage delivery. The NLC obtained by high-pressure homogenization showed low z-averages (<350 nm), polydispersity (<0.3), and encapsulation efficiency close to 100%. DSC/TG and microscopy in combination proved to be a powerful tool to select the solid lipid. The relationship among the variables, demonstrated by a linear mathematical model using RSM, allowed generating a design space. This design space showed the limits in which changes in the variables influenced the z-average. Therefore, these drug delivery systems have the potential to improve the availability of affordable medicines due to the low cost of raw materials, using well established, reliable, and feasible scale-up technology. PMID:28255558

Nano to micro delivery systems: targeting angiogenesis in brain tumors.

PubMed

Gilert, Ariel; Machluf, Marcelle

2010-10-08

Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary brain tumors, no clinical treatment is currently approved for brain tumor patients. One of the main hurdles in treating brain tumors is the blood brain barrier - a protective barrier of the brain, which prevents drugs from entering the brain parenchyma. As most therapeutics are excluded from the brain there is an urgent need to develop delivery platforms which will bypass such hurdles and enable the delivery of anti-angiogenic drugs into the tumor bed. Such delivery systems should be able to control release the drug or a combination of drugs at a therapeutic level for the desired time. In this mini-review we will discuss the latest improvements in nano and micro drug delivery platforms that were designed to deliver inhibitors of angiogenesis to the brain.

Nano to micro delivery systems: targeting angiogenesis in brain tumors

PubMed Central

2010-01-01

Treating brain tumors using inhibitors of angiogenesis is extensively researched and tested in clinical trials. Although anti-angiogenic treatment holds a great potential for treating primary and secondary brain tumors, no clinical treatment is currently approved for brain tumor patients. One of the main hurdles in treating brain tumors is the blood brain barrier - a protective barrier of the brain, which prevents drugs from entering the brain parenchyma. As most therapeutics are excluded from the brain there is an urgent need to develop delivery platforms which will bypass such hurdles and enable the delivery of anti-angiogenic drugs into the tumor bed. Such delivery systems should be able to control release the drug or a combination of drugs at a therapeutic level for the desired time. In this mini-review we will discuss the latest improvements in nano and micro drug delivery platforms that were designed to deliver inhibitors of angiogenesis to the brain. PMID:20932320

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

PubMed

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

2018-01-05

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

Adaptable Deployable Entry & Placement Technology (ADEPT) for Cubesat Delivery to Mars Surface

NASA Technical Reports Server (NTRS)

Wercinski, Paul

2014-01-01

The Adaptable, Deployable Entry and Placement Technology (ADEPT), uses a mechanical skeleton to deploy a revolutionary carbon fabric system that serves as both heat shield and primary structure during atmospheric entry. The NASA ADEPT project, currently funded by the Game Changing Development Program in STMD is currently focused on 1m class hypersonic decelerators for the delivery of very small payloads ( 5 kg) to locations of interest in an effort to leverage low-cost platforms to rapidly mature the technology while simultaneously delivering high-value science. Preliminary mission design and aerothermal performance testing in arcjets have shown the ADEPT system is quite capable of safe delivery of cubesats to Mars surface. The ability of the ADEPT to transit to Mars in a stowed configuration (similar to an umbrella) provides options for integration with the Mars 2020 cruise stage, even to consider multiple ADEPTs. System-level test campaigns are underway for FY15 execution or planning for FY16. These include deployment testing, wind tunnel testing, system-level arc jet testing, and a sounding rocket flight test. The goal is system level maturation (TRL 6) at a 1m class Mars design reference mission configuration.

Cognitive Models of Scientific Work and Their Implications for the Design of Knowledge Delivery Systems.

ERIC Educational Resources Information Center

Mavor, A. S.; And Others

Part of a sustained program that has involved the design of personally tailored information systems responsive to the needs of scientists performing common research and teaching tasks, this project focuses on the procedural and content requirements for accomplishing need diagnosis and presents these requirements as specifications for an…

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

PubMed

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

2015-11-01

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

Systematic Propulsion Optimization Tools (SPOT)

NASA Technical Reports Server (NTRS)

Bower, Mark; Celestian, John

1992-01-01

This paper describes a computer program written by senior-level Mechanical Engineering students at the University of Alabama in Huntsville which is capable of optimizing user-defined delivery systems for carrying payloads into orbit. The custom propulsion system is designed by the user through the input of configuration, payload, and orbital parameters. The primary advantages of the software, called Systematic Propulsion Optimization Tools (SPOT), are a user-friendly interface and a modular FORTRAN 77 code designed for ease of modification. The optimization of variables in an orbital delivery system is of critical concern in the propulsion environment. The mass of the overall system must be minimized within the maximum stress, force, and pressure constraints. SPOT utilizes the Design Optimization Tools (DOT) program for the optimization techniques. The SPOT program is divided into a main program and five modules: aerodynamic losses, orbital parameters, liquid engines, solid engines, and nozzles. The program is designed to be upgraded easily and expanded to meet specific user needs. A user's manual and a programmer's manual are currently being developed to facilitate implementation and modification.

Harnessing the potential of biomaterials for brain repair after stroke

NASA Astrophysics Data System (ADS)

Tuladhar, Anup; Payne, Samantha L.; Shoichet, Molly S.

2018-03-01

Stroke is a devastating disease for which no clinical treatment exists to regenerate lost tissue. Strategies for brain repair in animal models of stroke include the delivery of drug or cell-based therapeutics; however, the complex anatomy and functional organization of the brain presents many challenges. Biomaterials may alleviate some of these challenges by providing a scaffold, localizing the therapy to the site of action, and/or modulating cues to brain cells. Here, the challenges associated with delivery of therapeutics to the brain and the biomaterial strategies used to overcome these challenges are described. For example, innovative hydrogel delivery systems have been designed to provide sustained trophic factor delivery for endogenous repair and to support transplanted cell survival and integration. Novel treatments, such as electrical stimulation of transplanted cells and the delivery of factors for the direct reprogramming of astrocytes into neurons, may be further enhanced by biomaterial delivery systems. Ultimately, improved clinical translation will be achieved by combining clinically relevant therapies with biomaterials strategies.

Novel Strategies for Anterior Segment Ocular Drug Delivery

PubMed Central

Cholkar, Kishore; Patel, Sulabh P.; Vadlapudi, Aswani Dutt

2013-01-01

Abstract Research advancements in pharmaceutical sciences have led to the development of new strategies in drug delivery to anterior segment. Designing a new delivery system that can efficiently target the diseased anterior ocular tissue, generate high drug levels, and maintain prolonged and effective concentrations with no or minimal side effects is the major focus of current research. Drug delivery by traditional method of administration via topical dosing is impeded by ocular static and dynamic barriers. Various products have been introduced into the market that prolong drug retention in the precorneal pocket and to improve bioavailability. However, there is a need of a delivery system that can provide controlled release to treat chronic ocular diseases with a reduced dosing frequency without causing any visual disturbances. This review provides an overview of anterior ocular barriers along with strategies to overcome these ocular barriers and deliver therapeutic agents to the affected anterior ocular tissue with a special emphasis on nanotechnology-based drug delivery approaches. PMID:23215539

Feedback (F) Fueling Adaptation (A) Network Growth (N) and Self-Organization (S): A Complex Systems Design and Evaluation Approach to Professional Development

ERIC Educational Resources Information Center

Yoon, Susan A.; Klopfer, Eric

2006-01-01

This paper reports on the efficacy of a professional development framework premised on four complex systems design principles: Feedback, Adaptation, Network Growth and Self-organization (FANS). The framework is applied to the design and delivery of the first 2 years of a 3-year study aimed at improving teacher and student understanding of…

Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems--enhancement of oral bioavailability.

PubMed

Hashem, Fahima M; Al-Sawahli, Majid M; Nasr, Mohamed; Ahmed, Osama A A

2015-01-01

Poor water solubility of a drug is a major challenge in drug delivery research and a main cause for limited bioavailability and pharmacokinetic parameters. This work aims to utilize custom fractional factorial design to assess the development of self-nanoemulsifying drug delivery systems (SNEDDS) and solid nanosuspensions (NS) in order to enhance the oral delivery of atorvastatin (ATR). According to the design, 14 experimental runs of ATR SNEDDS were formulated utilizing the highly ATR solubilizing SNEDDS components: oleic acid, Tween 80, and propylene glycol. In addition, 12 runs of NS were formulated by the antisolvent precipitation-ultrasonication method. Optimized formulations of SNEDDS and solid NS, deduced from the design, were characterized. Optimized SNEDDS formula exhibited mean globule size of 73.5 nm, zeta potential magnitude of -24.1 mV, and 13.5 μs/cm of electrical conductivity. Optimized solid NS formula exhibited mean particle size of 260.3 nm, 7.4 mV of zeta potential, and 93.2% of yield percentage. Transmission electron microscopy showed SNEDDS droplets formula as discrete spheres. The solid NS morphology showed flaky nanoparticles with irregular shapes using scanning electron microscopy. The release behavior of the optimized SNEDDS formula showed 56.78% of cumulative ATR release after 10 minutes. Solid NS formula showed lower rate of release in the first 30 minutes. Bioavailability estimation in Wistar albino rats revealed an augmentation in ATR bioavailability, relative to ATR suspension and the commercial tablets, from optimized ATR SNEDDS and NS formulations by 193.81% and 155.31%, respectively. The findings of this work showed that the optimized nanocarriers enhance the oral delivery and pharmacokinetic profile of ATR.

Overcoming the Cutaneous Barrier with Microemulsions

PubMed Central

Lopes, Luciana B.

2014-01-01

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

Overcoming the Challenges of Implementing a Multi-Mission Distributed Workflow System

NASA Technical Reports Server (NTRS)

Sayfi, Elias; Cheng, Cecilia; Lee, Hyun; Patel, Rajesh; Takagi, Atsuya; Yu, Dan

2009-01-01

A multi-mission approach to solving the same problems for various projects is enticing. However, the multi-mission approach leads to the need to develop a configurable, adaptable and distributed system to meet unique project requirements. That, in turn, leads to a set of challenges varying from handling synchronization issues to coming up with a smart design that allows the "unknowns" to be decided later. This paper discusses the challenges that the Multi-mission Automated Task Invocation Subsystem (MATIS) team has come up against while designing the distributed workflow system, as well as elaborates on the solutions that were implemented. The first is to design an easily adaptable system that requires no code changes as a result of configuration changes. The number of formal deliveries is often limited because each delivery costs time and money. Changes such as the sequence of programs being called, a change of a parameter value in the program that is being automated should not result in code changes or redelivery.

The medicalization of addiction treatment professionals.

PubMed

Roy, A Kenison; Miller, Michael M

2012-01-01

In a previous article, the authors described the changes initiated by recent health care legislation, and how those changes might affect the practice of medicine and the delivery of addiction services. This article reviews the same changes with respect to how they have the potential to change the practice activities of addiction physicians, addiction therapists, addiction counselors and addiction nurses, as well as the activities of administrators and service delivery financial personnel. Developments in delivery systems and the impact of those developments on professionals who work in addiction treatment are considered; current problems, potential solutions, and opportunities for clinicians under health reform are addressed. The goals envisioned for health system reform and the potential for realization of those goals via changes in addiction service delivery design and clinical practice are discussed.

Unsteady jet in designing innovative drug delivery system

NASA Astrophysics Data System (ADS)

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

2014-11-01

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

A targeted drug delivery system based on dopamine functionalized nano graphene oxide

NASA Astrophysics Data System (ADS)

Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

2017-01-01

The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

Variability in syringe components and its impact on functionality of delivery systems.

PubMed

Rathore, Nitin; Pranay, Pratik; Eu, Bruce; Ji, Wenchang; Walls, Ed

2011-01-01

Prefilled syringes and autoinjectors are becoming increasingly common for parenteral drug administration primarily due to the convenience they offer to the patients. Successful commercialization of such delivery systems requires thorough characterization of individual components. Complete understanding of various sources of variability and their ranking is essential for robust device design. In this work, we studied the impact of variability in various primary container and device components on the delivery forces associated with syringe injection. More specifically, the effects of barrel size, needle size, autoinjector spring force, and frictional forces have been evaluated. An analytical model based on underlying physics is developed that can be used to fully characterize the design space for a product delivery system. Use of prefilled syringes (syringes prefilled with active drug) is becoming increasingly common for injectable drugs. Compared to vials, prefilled syringes offer higher dose accuracy and ease of use due to fewer steps required for dosage. Convenience to end users can be further enhanced through the use of prefilled syringes in combination with delivery devices such as autoinjectors. These devices allow patients to self-administer the drug by following simple steps such as pressing a button. These autoinjectors are often spring-loaded and are designed to keep the needle tip shielded prior to injection. Because the needle is not visible to the user, such autoinjectors are perceived to be less invasive than syringes and help the patient overcome the hesitation associated with self-administration. In order to successfully develop and market such delivery devices, we need to perform an in-depth analysis of the components that come into play during the activation of the device and dose delivery. Typically, an autoinjector is activated by the press of a button that releases a compressed spring; the spring relaxes and provides the driving force to push the drug out of the syringe and into the site of administration. Complete understanding of the spring force, syringe barrel dimensions, needle size, and drug product properties is essential for robust device design. It is equally important to estimate the extent of variability that exists in these components and the resulting impact it could have on the performance of the device. In this work, we studied the impact of variability in syringe and device components on the delivery forces associated with syringe injection. More specifically, the effect of barrel size, needle size, autoinjector spring force, and frictional forces has been evaluated. An analytical model based on underlying physics is developed that can be used to predict the functionality of the autoinjector.

Mucin-mediated nanocarrier disassembly for triggered uptake of oligonucleotides as a delivery strategy for the potential treatment of mucosal tumours

NASA Astrophysics Data System (ADS)

Martirosyan, A.; Olesen, M. J.; Fenton, R. A.; Kjems, J.; Howard, K. A.

2016-06-01

This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites.This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07206a

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

PubMed

Doroud, Delaram; Rafati, Sima

2012-01-01

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

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

PubMed Central

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

2012-01-01

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

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

PubMed

Ibsen, Stuart; Benchimol, Michael; Esener, Sadik

2013-01-01

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

Considerations for the Optimal Design of a Two-Way Interactive Distance Education Classroom.

ERIC Educational Resources Information Center

Gregg, Joe; Persichitte, Kay

To make effective use of a two-way interactive distance education system, classroom design should be a primary consideration. A properly designed classroom will enhance content objectives and increase acceptance of this type of instructional delivery. This paper describes key considerations for optimal design. Construction considerations include…

Corona-directed nucleic acid delivery into hepatic stellate cells for liver fibrosis therapy.

PubMed

Zhang, Zhengping; Wang, Chunming; Zha, Yinhe; Hu, Wei; Gao, Zhongfei; Zang, Yuhui; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

2015-03-24

Strategies to modify nanoparticles with biological ligands for targeted drug delivery in vivo have been widely studied but met with limited clinical success. A possible reason is that, in the blood circulation, serum proteins could rapidly form a layer of protein "corona" on the vehicle surface, which might block the modified ligands and hamper their targeting functions. We speculate that strategies for drug delivery can be designed based upon elegant control of the corona formation on the vehicle surfaces. In this study, we demonstrate a retinol-conjugated polyetherimine (RcP) nanoparticle system that selectively recruited the retinol binding protein 4 (RBP) in its corona components. RBP was found to bind retinol, and direct the antisense oligonucleotide (ASO)-laden RcP carrier to hepatic stellate cells (HSC), which play essential roles in the progression of hepatic fibrosis. In both mouse fibrosis models, induced by carbon tetrachloride (CCl4) and bile duct ligation (BDL), respectively, the ASO-laden RcP particles effectively suppressed the expression of type I collagen (collagen I), and consequently ameliorated hepatic fibrosis. Such findings suggest that this delivery system, designed to exploit the power of corona proteins, can serve as a promising tool for targeted delivery of therapeutic agents for the treatment of hepatic fibrosis.

Harnessing hospital purchase power to design safe care delivery.

PubMed

Ebben, Steven F; Gieras, Izabella A; Gosbee, Laura Lin

2008-01-01

Since the Institute of Medicine's well-publicized 1999 report To Err is Human, the healthcare patient safety movement has grown at an exponential pace. However, much more can be done to advance patient safety from a care process design vantage point-improving safety through effective care processes and technology integration. While progress is being made, the chasm between technology developers and caregivers remains a profound void. Why hasn't more been done to expand our view of patient safety to include technology design? Healthcare organizations have not consolidated their purchasing power to expect improved designs. This article will (1) provide an assessment of the present state of healthcare technology management and (2) provide recommendations for collaborative design of safe healthcare delivery systems.

Review of Spatial-Database System Usability: Recommendations for the ADDNS Project

DTIC Science & Technology

2007-12-01

basic GIS background information , with a closer look at spatial databases. A GIS is also a computer- based system designed to capture, manage...foundation for deploying enterprise-wide spatial information systems . According to Oracle® [18], it enables accurate delivery of location- based services...Toronto TR 2007-141 Lanter, D.P. (1991). Design of a lineage- based meta-data base for GIS. Cartography and Geographic Information Systems , 18

Learning Is the Journey: From Process Reengineering to Systemic Customer-Service Design at the United States Department of Veterans Affairs, Veterans Benefits Administration

DTIC Science & Technology

2013-05-23

This monograph borrows from multiple disciplines to argue for an organizational shift from process reengineering to system design to improve...government customer-service delivery. Specifically, the monograph proposes a transformation in claims processing within the Veterans Benefits Administration...required. The proposed system design is an attempt to place the disability claims process within a larger environment encompassing multiple dimensions of customers.

Floating drug delivery systems: a review.

PubMed

Arora, Shweta; Ali, Javed; Ahuja, Alka; Khar, Roop K; Baboota, Sanjula

2005-10-19

The purpose of writing this review on floating drug delivery systems (FDDS) was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. This review also summarizes the in vitro techniques, in vivo studies to evaluate the performance and application of floating systems, and applications of these systems. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form.

Targeted Delivery of siRNA to Activated T Cells via Transferrin-Polyethylenimine (Tf-PEI) as a Potential Therapy of Asthma

PubMed Central

Xie, Yuran; Kim, Na Hyung; Nadithe, Venkatareddy; Schalk, Dana; Thakur, Archana; Kılıç, Ayşe; Lum, Lawrence G.; Bassett, David JP; Merkel, Olivia M

2016-01-01

Asthma is a worldwide health problem. Activated T cells (ATCs) in the lung, particularly T helper 2 cells (Th2), are strongly associated with inducing airway inflammatory responses and chemoattraction of inflammatory cells in asthma. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence inflammation related genes in ATCs, however, lack of safe and efficient siRNA delivery systems limits the application of siRNA as a therapeutic molecule in asthma. Here, we designed a novel pulmonary delivery system of siRNA, transferrin-polyethylenimine (Tf-PEI), to selectively deliver siRNA to ATCs in the lung. Tf-PEI polyplexes demonstrated optimal physicochemical properties such as size, distribution, zeta-potential, and siRNA condensation efficiency. Moreover, in vitro studies showed significantly enhanced cellular uptake and gene knockdown mediated by Tf-PEI polyplexes in human primary ATCs. Biodistribution of polyplexes in a murine asthmatic model confirmed that Tf-PEI polyplexes can efficiently and selectively deliver siRNA to ATCs. In conclusion, the present work proves the feasibility to target ATCs in asthma via Tf receptor. This strategy could potentially be used to design an efficient siRNA delivery system for asthma therapy. PMID:27001893

Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma.

PubMed

Xie, Yuran; Kim, Na Hyung; Nadithe, Venkatareddy; Schalk, Dana; Thakur, Archana; Kılıç, Ayşe; Lum, Lawrence G; Bassett, David J P; Merkel, Olivia M

2016-05-10

Asthma is a worldwide health problem. Activated T cells (ATCs) in the lung, particularly T helper 2 cells (Th2), are strongly associated with inducing airway inflammatory responses and chemoattraction of inflammatory cells in asthma. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence inflammation related genes in ATCs, however, lack of safe and efficient siRNA delivery systems limits the application of siRNA as a therapeutic molecule in asthma. Here, we designed a novel pulmonary delivery system of siRNA, transferrin-polyethylenimine (Tf-PEI), to selectively deliver siRNA to ATCs in the lung. Tf-PEI polyplexes demonstrated optimal physicochemical properties such as size, distribution, zeta-potential, and siRNA condensation efficiency. Moreover, in vitro studies showed significantly enhanced cellular uptake and gene knockdown mediated by Tf-PEI polyplexes in human primary ATCs. Biodistribution of polyplexes in a murine asthmatic model confirmed that Tf-PEI polyplexes can efficiently and selectively deliver siRNA to ATCs. In conclusion, the present work proves the feasibility to target ATCs in asthma via Tf receptor. This strategy could potentially be used to design an efficient siRNA delivery system for asthma therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors.

PubMed

Stylianopoulos, Triantafyllos; Economides, Eva-Athena; Baish, James W; Fukumura, Dai; Jain, Rakesh K

2015-09-01

Conventional drug delivery systems for solid tumors are composed of a nano-carrier that releases its therapeutic load. These two-stage nanoparticles utilize the enhanced permeability and retention (EPR) effect to enable preferential delivery to tumor tissue. However, the size-dependency of the EPR, the limited penetration of nanoparticles into the tumor as well as the rapid binding of the particles or the released cytotoxic agents to cancer cells and stromal components inhibit the uniform distribution of the drug and the efficacy of the treatment. Here, we employ mathematical modeling to study the effect of particle size, drug release rate and binding affinity on the distribution and efficacy of nanoparticles to derive optimal design rules. Furthermore, we introduce a new multi-stage delivery system. The system consists of a 20-nm primary nanoparticle, which releases 5-nm secondary particles, which in turn release the chemotherapeutic drug. We found that tuning the drug release kinetics and binding affinities leads to improved delivery of the drug. Our results also indicate that multi-stage nanoparticles are superior over two-stage nano-carriers provided they have a faster drug release rate and for high binding affinity drugs. Furthermore, our results suggest that smaller nanoparticles achieve better treatment outcome.

Uniform Surface Modification of 3D Bioglass®-Based Scaffolds with Mesoporous Silica Particles (MCM-41) for Enhancing Drug Delivery Capability

PubMed Central

Boccardi, Elena; Philippart, Anahí; Juhasz-Bortuzzo, Judith A.; Beltrán, Ana M.; Novajra, Giorgia; Vitale-Brovarone, Chiara; Spiecker, Erdmann; Boccaccini, Aldo R.

2015-01-01

The design and characterization of a new family of multifunctional scaffolds based on bioactive glass (BG) of 45S5 composition for bone tissue engineering and drug delivery applications are presented. These BG-based scaffolds are developed via a replication method of polyurethane packaging foam. In order to increase the therapeutic functionality, the scaffolds were coated with mesoporous silica particles (MCM-41), which act as an in situ drug delivery system. These sub-micron spheres are characterized by large surface area and pore volume with a narrow pore diameter distribution. The solution used for the synthesis of the silica mesoporous particles was designed to obtain a high-ordered mesoporous structure and spherical shape – both are key factors for achieving the desired controlled drug release. The MCM-41 particles were synthesized directly inside the BG-based scaffolds, and the drug-release capability of this combined system was evaluated. Moreover, the effect of MCM-41 particle coating on the bioactivity of the BG-based scaffolds was assessed. The results indicate that it is possible to obtain a multifunctional scaffold system characterized by high and interconnected porosity, high bioactivity, and sustained drug delivery capability. PMID:26594642

NanoClusters Enhance Drug Delivery in Mechanical Ventilation

NASA Astrophysics Data System (ADS)

Pornputtapitak, Warangkana

The overall goal of this thesis was to develop a dry powder delivery system for patients on mechanical ventilation. The studies were divided into two parts: the formulation development and the device design. The pulmonary system is an attractive route for drug delivery since the lungs have a large accessible surface area for treatment or drug absorption. For ventilated patients, inhaled drugs have to successfully navigate ventilator tubing and an endotracheal tube. Agglomerates of drug nanoparticles (also known as 'NanoClusters') are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. This Thesis systematically investigated formulations of NanoClusters and their aerosol performance in a conventional inhaler and a device designed for use during mechanical ventilation. These engineered powders of budesonide (NC-Bud) were delivered via a MonodoseRTM inhaler or a novel device through commercial endotracheal tubes, and analyzed by cascade impaction. NC-Bud had a higher efficiency of aerosol delivery compared to micronized stock budesonide. The delivery efficiency was independent of ventilator parameters such as inspiration patterns, inspiration volumes, and inspiration flow rates. A novel device designed to fit directly to the ventilator and endotracheal tubing connections and the MonodoseRTM inhaler showed the same efficiency of drug delivery. The new device combined with NanoCluster formulation technology, therefore, allowed convenient and efficient drug delivery through endotracheal tubes. Furthermore, itraconazole (ITZ), a triazole antifungal agent, was formulated as a NanoCluster powder via milling (top-down process) or precipitation (bottom-up process) without using any excipients. ITZ NanoClusters prepared by wet milling showed better aerosol performance compared to micronized stock ITZ and ITZ NanoClusters prepared by precipitation. ITZ NanoClusters prepared by precipitation methods also showed an amorphous state while milled ITZ NanoClusters maintained the crystalline character. Overall, NanoClusters prepared by various processes represent a potential engineered drug particle approach for inhalation therapy since they provide effective aerosol properties and stability due to the crystalline state of the drug powders. Future work will continue to explore formulation and delivery performance in vitro and in vivo..

Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi

2011-01-01

An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

Influence of hydroxypropyl methylcellulose on drug release pattern of a gastroretentive floating drug delivery system using a 3(2) full factorial design.

PubMed

Swain, Kalpana; Pattnaik, Satyanarayan; Mallick, Subrata; Chowdary, Korla Appana

2009-01-01

In the present investigation, controlled release gastroretentive floating drug delivery system of theophylline was developed employing response surface methodology. A 3(2) randomized full factorial design was developed to study the effect of formulation variables like various viscosity grades and contents of hydroxypropyl methylcellulose (HPMC) and their interactions on response variables. The floating lag time for all nine experimental trial batches were less than 2 min and floatation time of more than 12 h. Theophylline release from the polymeric matrix system followed non-Fickian anomalous transport. Multiple regression analysis revealed that both viscosity and content of HPMC had statistically significant influence on all dependent variables but the effect of these variables found to be nonlinear above certain threshold values.

Designing for International Teletraining.

ERIC Educational Resources Information Center

Chute, Alan G.; Shatzer, Linda S.

The ability to bridge together geographically-distant populations for training is made possible through teletraining, a human performance system which integrates telecommunications into the planning, design, and delivery of training programs. Typically, teletraining uses standard telephone lines or digital communication services to provide…

Optimized Delivery System Achieves Enhanced Endomyocardial Stem Cell Retention

PubMed Central

Behfar, Atta; Latere, Jean-Pierre; Bartunek, Jozef; Homsy, Christian; Daro, Dorothee; Crespo-Diaz, Ruben J.; Stalboerger, Paul G.; Steenwinckel, Valerie; Seron, Aymeric; Redfield, Margaret M.; Terzic, Andre

2014-01-01

Background Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention. Methods and Results Stem cell retention was simulated in silico using one and three-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol – a nickel and titanium alloy displaying shape memory and super-elasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared to a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle, without impact on biocompatibility or safety. Conclusions Modeling guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention. PMID:24326777

Health care delivery system reform: accountable care organizations.

PubMed

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

2009-09-08

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

Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment.

PubMed

Liu, Jia; Qi, Chao; Tao, Kaixiong; Zhang, Jinxiang; Zhang, Jian; Xu, Luming; Jiang, Xulin; Zhang, Yunti; Huang, Lei; Li, Qilin; Xie, Hongjian; Gao, Jinbo; Shuai, Xiaoming; Wang, Guobin; Wang, Zheng; Wang, Lin

2016-03-01

Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross-linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericin's photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems.

Ion-Responsive Drug Delivery Systems.

PubMed

Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

2018-02-08

Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

PubMed

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

2016-09-01

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

Cell-Mediated Drugs Delivery

PubMed Central

Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

2011-01-01

INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

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

Sequential delivery of TAT-HSP27 and VEGF using microsphere/hydrogel hybrid systems for therapeutic angiogenesis.

PubMed

Shin, Seung-Hwa; Lee, Jangwook; Lim, Kwang Suk; Rhim, Taiyoun; Lee, Sang Kyung; Kim, Yong-Hee; Lee, Kuen Yong

2013-02-28

Ischemic disease is associated with high mortality and morbidity rates, and therapeutic angiogenesis via systemic or local delivery of protein drugs is one potential approach to treat the disease. In this study, we hypothesized that combined delivery of TAT-HSP27 (HSP27 fused with transcriptional activator) and VEGF could enhance the therapeutic efficacy in an ischemic mouse model, and that sequential release could be critical in therapeutic angiogenesis. Alginate hydrogels containing TAT-HSP27 as an anti-apoptotic agent were prepared, and porous PLGA microspheres loaded with VEGF as an angiogenic agent were incorporated into the hydrogels to prepare microsphere/hydrogel hybrid delivery systems. Sequential in vitro release of TAT-HSP27 and VEGF was achieved by the hybrid systems. TAT-HSP27 was depleted from alginate gels in 7 days, while VEGF was continually released for 28 days. The release rate of VEGF was attenuated by varying the porous structures of PLGA microspheres. Sequential delivery of TAT-HSP27 and VEGF was critical to protect against muscle degeneration and fibrosis, as well as to promote new blood vessel formation in the ischemic site of a mouse model. This approach to controlling the sequential release behaviors of multiple drugs could be useful in the design of novel drug delivery systems for therapeutic angiogenesis. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluating Learning Management System (LMS)-Facilitated Delivery of Universal Design for Learning (UDL)

ERIC Educational Resources Information Center

Bryans Bongey, Sarah

2012-01-01

This quantitative study involved 157 students in two sections of an undergraduate class in general biology, as well as one instructor who taught both sections of the course. It used resources from the Center for Applied Special Technologies (CAST) to evaluate the viability of a Learning Management System (LMS) to provide Universal Design for…

Structural design considerations for the beam transmission optical system

NASA Technical Reports Server (NTRS)

Macneal, Paul D.; Lou, Michael C.

1993-01-01

The paper describes the JPL study leading to a baseline design of the Beam Transmission Optical System (BTOS), designed for the delivery of laser energy from earth to space targets. The study identified the driving environmental and functional requirements; developed a conceptual design of the BTOS telescope; and performed static, thermal distortion, and model analyses to verify that these requirements are met. The study also identified major areas of concern which should be investigated further.

Hydrogels for central nervous system therapeutic strategies.

PubMed

Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

2015-12-01

The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described. © IMechE 2015.

Pharmacogenomics in the preclinical development of vaccines: evaluation of efficacy and systemic toxicity in the mouse using array technology.

PubMed

Regnström, Karin J

2008-01-01

The development of vaccines, conventional protein based as well as nucleic acid based vaccines, and their delivery systems has been largely empirical and ineffective. This is partly due to a lack of methodology, since traditionally only a few markers are studied. By introducing gene expression analysis and bioinformatics into the design of vaccines and their delivery systems, vaccine development can be improved and accelerated considerably. Each vaccine antigen and delivery system combination is characterized by a unique genomic profile, a "fingerprint" that will give information of not only immunological and toxicological responses but also other related cellular responses e.g. cell cycle, apoptosis and carcinogenic effects. The resulting unique genomic fingerprint facilitates the establishment of molecular structure--pharmacological activity relationships and therefore leads to optimization of vaccine development.

Recent technologies in pulsatile drug delivery systems

PubMed Central

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

2011-01-01

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

Development of oral food-grade delivery systems: current knowledge and future challenges.

PubMed

Benshitrit, Revital Cohen; Levi, Carmit Shani; Tal, Sharon Levi; Shimoni, Eyal; Lesmes, Uri

2012-01-01

In recent years there has been an increasing interest in the development of new and efficient oral food delivery systems as tools to prevent disease and promote human health and well-being. Such vehicles are sought to protect bioactive ingredients added to food while controlling and targeting their release as they pass through the human gastrointestinal tract (GIT). This review aims to summarize the key concepts of food delivery systems, their characterization and evaluation. Particularly, evaluation of their performance within the human GIT is discussed. To this end an overview of several in vivo and in vitro methods currently applied for the study of such systems is given. Although considered to be still in its infancy, this promising field of research is likely to infiltrate into real products through rational design. In order for such efforts to materialize into real products some challenges still need to be met and are discussed herein. Overall, it seems that adopting a comprehensive pharmacological approach and relevant cutting edge tools are likely to facilitate innovations and help elucidate and perhaps tailor delivery systems' behavior in the human GIT.

Chitosan-palmitic acid based polymeric micelles as promising carrier for circumventing pharmacokinetic and drug delivery concerns of tamoxifen.

PubMed

Thotakura, Nagarani; Dadarwal, Mukesh; Kumar, Rajendra; Singh, Bhupinder; Sharma, Gajanand; Kumar, Pramod; Katare, Om Prakash; Raza, Kaisar

2017-09-01

Being a BCS class II drug and a good substrate for microsomal enzymes, tamoxifen (TAM) offers a scope for research owing to poor aqueous solubility and compromised bioavailability. The present study designs a novel copolymer derived from palmitic acid and chitosan, and evaluate the derived TAM-loaded micelles for various delivery attributes. The nanometric micellar carriers not only substantially loaded the drug, but also controlled the rate of release of TAM. The designed nanocarrier significantly enhanced the cytotoxicity of TAM on MCF-7 cancer cells. The developed system was designed for intravenous route and was observed to be substantially haemo-compatible with an enhancement of approx. 5 times in AUC vis-a-vis plain drug. The findings employing new polymer-based carrier are promising in nature for the better delivery of similar drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and optimization of resonance-based efficient wireless power delivery systems for biomedical implants.

PubMed

Ramrakhyani, A K; Mirabbasi, S; Mu Chiao

2011-02-01

Resonance-based wireless power delivery is an efficient technique to transfer power over a relatively long distance. This technique typically uses four coils as opposed to two coils used in conventional inductive links. In the four-coil system, the adverse effects of a low coupling coefficient between primary and secondary coils are compensated by using high-quality (Q) factor coils, and the efficiency of the system is improved. Unlike its two-coil counterpart, the efficiency profile of the power transfer is not a monotonically decreasing function of the operating distance and is less sensitive to changes in the distance between the primary and secondary coils. A four-coil energy transfer system can be optimized to provide maximum efficiency at a given operating distance. We have analyzed the four-coil energy transfer systems and outlined the effect of design parameters on power-transfer efficiency. Design steps to obtain the efficient power-transfer system are presented and a design example is provided. A proof-of-concept prototype system is implemented and confirms the validity of the proposed analysis and design techniques. In the prototype system, for a power-link frequency of 700 kHz and a coil distance range of 10 to 20 mm, using a 22-mm diameter implantable coil resonance-based system shows a power-transfer efficiency of more than 80% with an enhanced operating range compared to ~40% efficiency achieved by a conventional two-coil system.

Development and evaluation of thymol-chitosan hydrogels with antimicrobial-antioxidant activity for oral local delivery.

PubMed

Alvarez Echazú, María Inés; Olivetti, Christian Ezequiel; Anesini, Claudia; Perez, Claudio Javier; Alvarez, Gisela Solange; Desimone, Martin Federico

2017-12-01

Nowadays, the research of innovative drug delivery devices is focused on the design of multiple drug delivery systems, the prevention of drug side effects and the reduction of dosing intervals. Particularly, new mucosal delivery systems for antimicrobials, antioxidants and anti-inflammatory drugs has a growing development, regards to the avoidance of side effects, easy administration and a suitable drug concentration in the mucosa. In this work, chitosan hydrogels are evaluated as a biodegradable scaffold and as a bioactive agent carrier of an antioxidant-antimicrobial compound called thymol. Throughout the study, swelling behavior, viscoelastic properties and thermal analysis are highlighted to present its advantages for a biomedical application. Furthermore, the in vitro results obtained indicate that thymol-chitosan hydrogels are biocompatible when exposed to [3T3] fibroblasts, exhibit antimicrobial activity against Staphylococcus aureus and Streptococcus mutans for 72h and antioxidant activity for 24h. These are desirable properties for a mucosal delivery system for an antimicrobial-antioxidant dual therapy for periodontal disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulatory aspects in the pharmaceutical development of nanoparticle drug delivery systems designed to cross the intestinal epithelium and M-cells.

PubMed

Hussain, Nasir

2016-11-30

This article reviews the field of oral uptake of nanoparticles across the gastrointestinal epithelium for the period 2006-2016. Analysis is conducted from the viewpoint of i) M-cell genetics and model development, ii) drug targeting to Peyer's patches and M-cells, and iii) physicochemical interactions of nanoparticles in the intestinal milieu. In light of these recent developments, regulatory considerations in the development of orally-absorbable nanoparticle drug products are discussed and focused on Module 3.2.P sub-sections of the Common Technical Document. Particular attention is paid to novel excipients, ligands and the non-standard method of manufacture. The novelty of this drug delivery system demands not only a multi-disciplinary scientific and regulatory approach but also a risk-adjusted consideration for a system defined by both processes and specifications. Given the current state of scientific development in the field it is suggested (in the author's personal opinion) that the design of nanoparticulate drug delivery systems should be kept as simple as possible (from a regulatory and manufacturing perspective) and to target the entire gastrointestinal epithelium. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Particulate delivery systems for biodefense subunit vaccines.

PubMed

Bramwell, Vincent W; Eyles, Jim E; Oya Alpar, H

2005-06-17

Expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. Despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. This review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, against potential agents for biowarfare: plague, anthrax, botulinum, and smallpox; and filoviruses: Marburg and Ebola.

Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride.

PubMed

Verma, Anurag; Bansal, Ashok K; Ghosh, Amitava; Pandit, Jayanta K

2012-06-01

Chitosan has become a focus of major interest in recent years due to its excellent biocompatibility, biodegradability and non-toxicity. Although this material has already been extensively investigated in the design of different types of drug delivery systems, it is still little explored for stomach specific drug delivery systems. The objective of the present investigation was to explore the potential of low molecular mass chitosan (LMCH) as carrier for a hydrodynamically balanced system (HBS) for sustained delivery of water soluble drug ciprofloxacin hydrochloride (CP). Various formulations were prepared by physical blending of drug and polymer(s) in varying ratios followed by encapsulation into hard gelatin capsules. All the formulations remained buoyant in 0.1 mol L⁻¹ HCl (pH 1.2) throughout the experiment. Effect of addition of xanthan gum (XG) or ethyl cellulose (EC) on drug release was also investigated. Zero order drug release was obtained from the formulations containing LMCH alone or in combination with XG, and in one instance also with EC. Our results suggest that LMCH alone or in combination with XG is an excellent material for stomach specific sustained delivery of CP from hydrodynamically balanced single unit capsules.

Multifunctional, chitosan-based nano therapeutics: design and application for two- and three-dimensional cell culture systems

NASA Astrophysics Data System (ADS)

Suarato, Giulia

There is a constant demand for sensitive and effective anti-cancer drug delivery systems, capable of detecting early-stage pathological conditions and increasing patient survival. Recently, chitosan-based drug delivery nanocomplexes have shown to smartly respond to the distinctive features of the tumor microenvironment, a complex network of extracellular molecules, stromal and endothelial cells, which supports the tumor formation and its metastatic invasion. Due to biocompatibility, easy chemical tailorability, and pH-responsiveness, chitosan has emerged as a promising candidate for the formulation of supramolecular multifunctional materials. The present study focuses on the design, fabrication and characterization of fluorescently labelled, hydrophobically modified glycol chitosan nano-micelles (HGC NPs), suitably tailored for the delivery of anti-neoplastic compounds to various tumor models. Doxorubicin-loaded HGC NPs have been delivered to a bone cancer model, both in monolayer and in 3D spheroid configuration, to assess for differences in the delivery profiles and in the therapeutic efficacy. Compared to the free drug, nanocomplexes showed rapid uptake and a more homogeneous distribution in 3D spheroids, a powerful cellular tool which recapitulates some of the in vivo tumor microenvironment features. In a second part of this thesis work, with the purpose of designing an active targeting tumor-homing nano-therapeutic system, HGC NPs have been linked, via avidin-biotin interaction, with a IVS4 peptide, a small molecule with inhibitory activity on MMP-14-mediated functions. An extensive study conducted on triple negative breast cancer cells in monolayer revealed the MMP-14-IVS4-HGC association at the cancer cell membrane, the preferential uptake, and the consequent impairment of protease-associated migratory ability. As an additional application of our engineered construct, HGC micelles have been decorated with a liver kinase B1 (LKB1), a critical kinase involved in neuronal cell polarization, with the aim of regulating axon development. Our preliminary data indicated that, when treated with HGC-LKB1 NPs, primary ray embryo hippocampal neurons in vitro presented a multiple axon phenotype, validating the potential use of our multifunctional system as local protein delivery agent. In addition, we successfully performed for the first time in utero electroporation delivery of the chitosan nano-micelles, demonstrating the in vivo uptake potential of our system.

48 CFR 52.247-44 - F.o.b. Designated Air Carrier's Terminal, Point of Importation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false F.o.b. Designated Air... CLAUSES Text of Provisions and Clauses 52.247-44 F.o.b. Designated Air Carrier's Terminal, Point of... the delivery term is f.o.b. designated air carrier's terminal, point of importation: F.o.b. Designated...

48 CFR 52.247-43 - F.o.b. Designated Air Carrier's Terminal, Point of Exportation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false F.o.b. Designated Air... CLAUSES Text of Provisions and Clauses 52.247-43 F.o.b. Designated Air Carrier's Terminal, Point of... the delivery term is f.o.b. designated air carrier's terminal, point of exportation: F.o.b. Designated...

Patient-centredness in integrated healthcare delivery systems - needs, expectations and priorities for organised healthcare systems

PubMed Central

Juhnke, Christin; Mühlbacher, Axel C.

2013-01-01

Introduction Patient-centred healthcare is becoming a more significant success factor in the design of integrated healthcare systems. The objective of this study is to structure a patient-relevant hierarchy of needs and expectations for the design of organised healthcare delivery systems. Methods A questionnaire with 84 items was conducted with N = 254 healthcare experts and N = 670 patients. Factor analyses were performed using SPSS©18. The number of factors retained was controlled by Kaiser's criterion, validation of screeplots and interpretability of the items. Cronbach's α was used to assess the internal consistency of the subscales. Results Exploratory factor analysis led to 24 factors in the expert sample and 20 in the patient sample. After analysing the screeplots, confirmatory factor analyses were computed for 7-factor solutions accounting for 42.963% of the total variance and Kaiser–Meyer–Olkin of 0.914 for the patients (experts: 38.427%, Kaiser–Meyer–Olkin = 0.797). Cronbach's α ranged between 0.899 and 0.756. Based on the analysis, coordinated care could be differentiated into seven dimensions: access, data and information, service and infrastructure, professional care, interpersonal care, individualised care, continuity and coordination. Conclusion and Discussion The study provides insight into patient and experts expectations towards the organisation of integrated healthcare delivery systems. If providers and payers can take into account patient needs and expectations while implementing innovative healthcare delivery systems, greater acceptance and satisfaction will be achieved. In the best case, this will lead to better adherence resulting in better clinical outcomes. PMID:24363639

Diffusion-Based Design of Multi-Layered Ophthalmic Lenses for Controlled Drug Release

PubMed Central

Pimenta, Andreia F. R.; Serro, Ana Paula; Paradiso, Patrizia; Saramago, Benilde

2016-01-01

The study of ocular drug delivery systems has been one of the most covered topics in drug delivery research. One potential drug carrier solution is the use of materials that are already commercially available in ophthalmic lenses for the correction of refractive errors. In this study, we present a diffusion-based mathematical model in which the parameters can be adjusted based on experimental results obtained under controlled conditions. The model allows for the design of multi-layered therapeutic ophthalmic lenses for controlled drug delivery. We show that the proper combination of materials with adequate drug diffusion coefficients, thicknesses and interfacial transport characteristics allows for the control of the delivery of drugs from multi-layered ophthalmic lenses, such that drug bursts can be minimized, and the release time can be maximized. As far as we know, this combination of a mathematical modelling approach with experimental validation of non-constant activity source lamellar structures, made of layers of different materials, accounting for the interface resistance to the drug diffusion, is a novel approach to the design of drug loaded multi-layered contact lenses. PMID:27936138

Ocular drug metabolism of the bioactivating antioxidant N-acetylcarnosine for vision in ophthalmic prodrug and codrug design and delivery.

PubMed

Babizhayev, Mark A

2008-10-01

The basic idea in this study relates to the interesting research problem to employ with the knowledgeable pharmacy staff N-acetylcarnosine (NAC) in the developed suitable compounded prodrug ophthalmic preparations, which are currently used for the treatment of cataract and have antioxidant effect, in order to provide the molecular support to one of the most popular beliefs of the growing market for the treatment of senile cataract in patients and animals with efficacious NAC drug formulations worldwide patented by the author. This work presents the progress in ocular NAC prodrug and codrug design and delivery in light of revealed ocular metabolic activities. There is a considerable interest in the ophthalmic codrug design including NAC prodrug based on the strategies to improve ophthalmic drug delivery of the active peptide principal L-carnosine through the sustained intraocular metabolic activation of a dipeptide while making it resistant to enzymatic hydrolysis. Novel approaches to ocular NAC drug delivery, developed by Innovative Vision Products, Inc. (IVP), aim at enhancing the drug bioavailability by ensuring a prolonged retention of the medication in the eye, and/or by facilitating transcorneal penetration. IVP team studied the effects of lubricant eye drops designed as 1% NAC prodrug of L-carnosine containing a mucoadhesive cellulose-based and corneal absorption promoters in a drug delivery system. The predicted responses of the corneal and conjunctival penetrations to the synergistic promoters are useful in controlling the extent and pathway of the ocular and systemic absorptions of instilled NAC prodrug in designed ophthalmic formulations thereof. Utility of peptidase enzyme inhibitors in the codrug formulation to modulate the transport and metabolism of NAC prodrug appears to be a promising strategy for enhancing dipeptide drug transport across the cornea. The developed and officially CE mark registered by IVP NAC prodrug and codrug lubricating eye drop systems (including principal regulatory registered eye drops design and lubricating eye drops marketed under numerous brand labels), increase the intraocular uptake of the active principle L-carnosine from its ophthalmic carrier NAC in the aqueous humor and the permeability of a drug into the eye, and so enhance the ocular bioavailability, bioactivating universal antioxidant, and anti-cataract efficacy (in human and in canine eyes) of the developed NAC eye drops.

Laser beam distribution system for the HiLASE Center

NASA Astrophysics Data System (ADS)

Macúchová, Karolina; Heřmánek, Jan; Kaufman, Jan; Muresan, Mihai-George; Růžička, Jan; Řeháková, Martina; Divoký, Martin; Švandrlík, Luděk.; Mocek, Tomáś

2017-12-01

We report recent progress in design and testing of a distribution system for high-power laser beam delivery developed within the HiLASE project of the IOP in the Czech Republic. Laser beam distribution system is a technical system allowing safe and precise distribution of different laser beams from laboratories to several experimental stations. The unique nature of HiLASE lasers requires new approach, which makes design of the distribution system a state-of-the-art challenge.

Design Knowledge Management System (DKMS) Beta Test Report

DTIC Science & Technology

1992-11-01

design process. These problems, which include knowledge representation, constraint propagation, model design, and information integration, are...effective delivery of life-cycle engineering knowledge assistance and information to the design/engineering activities. It does not matter whether these...platfomi. 4. Reuse - existing data, information , and knowledge can be reused. 5. Remote Execution -- automatically handles remote execution without

The next step in gene delivery: molecular engineering of adeno-associated virus serotypes.

PubMed

Wang, Jinhui; Faust, Susan M; Rabinowitz, Joseph E

2011-05-01

Delivery is at the heart of gene therapy. Viral DNA delivery systems are asked to avoid the immune system, transduce specific target cell types while avoiding other cell types, infect dividing and non-dividing cells, insert their cargo within the host genome without mutagenesis or to remain episomal, and efficiently express transgenes for a substantial portion of a lifespan. These sought-after features cannot be associated with a single delivery system, or can they? The Adeno-associated virus family of gene delivery vehicles has proven to be highly malleable. Pseudotyping, using AAV serotype 2 terminal repeats to generate designer shells capable of transducing selected cell types, enables the packaging of common genomes into multiple serotypes virions to directly compare gene expression and tropism. In this review the ability to manipulate this virus will be examined from the inside out. The influence of host cell factors and organism biology including the immune response on the molecular fate of the viral genome will be discussed as well as differences in cellular trafficking patterns and uncoating properties that influence serotype transduction. Re-engineering the prototype vector AAV2 using epitope insertion, chemical modification, and molecular evolution not only demonstrated the flexibility of the best-studied serotype, but now also expanded the tool kit for molecular modification of all AAV serotypes. Current AAV research has changed its focus from examination of wild-type AAV biology to the feedback of host cell/organism on the design and development of a new generation of recombinant AAV delivery vehicles. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy". Copyright © 2010 Elsevier Ltd. All rights reserved.

SU-D-BRD-01: An Automated Physics Weekly Chart Checking System Supporting ARIA

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

Chang, X; Yang, D

Purpose: A software tool was developed in this study to perform automatic weekly physics chart check on the patient data in ARIA. The tool accesses the electronic patient data directly from ARIA server and checks the accuracy of treatment deliveries, and generates reports which summarize the delivery history and highlight the errors. Methods: The tool has four modules. 1) The database interface is designed to directly access treatment delivery data from the ARIA database before reorganizing the data into the patient chart tree (PCT). 2) PCT is a core data structure designed to store and organize the data in logicalmore » hierarchies, and to be passed among functions. 3) The treatment data check module analyzes the organized data in PCT and stores the checking results into PCT. 4) Report generation module generates reports containing the treatment delivery summary, chart checking results and plots of daily treatment setup parameters (couch table positions, shifts of image guidance). The errors that are found by the tool are highlighted with colors. Results: The weekly check tool has been implemented in MATLAB and clinically tested at two major cancer centers. Javascript, cascading style sheets (CSS) and dynamic HTML were employed to create the user-interactive reports. It takes 0.06 second to search the delivery records of one beam with PCT and compare the delivery records with beam plan. The reports, saved in the HTML files on shared network folder, can be accessed by web browser on computers and mobile devices. Conclusion: The presented weekly check tool is useful to check the electronic patient treatment data in Varian ARIA system. It could be more efficient and reliable than the manually check by physicists. The work was partially supported by a research grant from Varian Medical System.« less

Lipid based delivery and immuno-stimulatory systems: Master tools to combat leishmaniasis.

PubMed

Sabur, Abdus; Asad, Mohammad; Ali, Nahid

2016-11-01

Disease management of leishmaniasis is appalling due to lack of a human vaccine and the toxicity and resistance concerns with limited therapeutic drugs. The challenges in development of a safe vaccine for generation and maintenance of robust antileishmanial protective immunity through a human administrable route of immunization can be addressed through immunomodulation and targeted delivery. The versatility of lipid based particulate system for deliberate delivery of diverse range of molecules including immunomodulators, antigens and drugs have essentially found pivotal role in design of proficient vaccination and therapeutic strategies against leishmaniasis. The prospects of lipid based preventive and curative formulations for leishmaniasis have been highlighted in this review. Copyright © 2016. Published by Elsevier Inc.

A method for evaluating nanoparticle transport through the blood-brain barrier in vitro.

PubMed

Guarnieri, Daniela; Muscetti, Ornella; Netti, Paolo A

2014-01-01

Blood-brain barrier (BBB) represents a formidable barrier for many therapeutic drugs to enter the brain tissue. The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous system (CNS) diseases. In this context, nanoparticles are an emerging class of drug delivery systems that can be easily tailored to deliver drugs to various compartments of the body, including the brain. To identify, characterize, and validate novel nanoparticles applicable to brain delivery, in vitro BBB model systems have been developed. In this work, we describe a method to screen nanoparticles with variable size and surface functionalization in order to define the physicochemical characteristics underlying the design of nanoparticles that are able to efficiently cross the BBB.

Modular design of H - synchrotrons for radiation therapy

NASA Astrophysics Data System (ADS)

Martin, R. L.

1989-04-01

A modular synchrotron for accelerating H - ions and a proton beam delivery system are being developed for radiation therapy with protons under SBIR grants from the National Cancer Institute. The advantage proposed for accelerating H - ions and utilizing charge exchange as a slow extraction mechanism lies in enhanced control of the extracted beam current, important for beam delivery with raster scanning for 3D dose contouring of a tumor site. Under these grants prototype magnets and vacuum systems are being constructed, appropriate H - sources are being developed and beam experiments will be carried out to demonstrate some of the key issues of this concept. The status of this program is described along with a discussion of a relatively inexpensive beam delivery system and a proposed program for its development.

Unmanned Aerial System (UAS) Traffic Management (UTM): Enabling Low-Altitude Airspace and UAS Operations

NASA Technical Reports Server (NTRS)

Kopardekar, Parimal H.

2014-01-01

Many civilian applications of Unmanned Aerial Systems (UAS) have been imagined ranging from remote to congested urban areas, including goods delivery, infrastructure surveillance, agricultural support, and medical services delivery. Further, these UAS will have different equipage and capabilities based on considerations such as affordability, and mission needs applications. Such heterogeneous UAS mix, along with operations such as general aviation, helicopters, gliders must be safely accommodated at lower altitudes. However, key infrastructure to enable and safely manage widespread use of low-altitude airspace and UAS operations therein does not exist. Therefore, NASA is exploring functional design, concept and technology development, and a prototype UAS Traffic Management (UTM) system. UTM will support safe and efficient UAS operations for the delivery of goods and services

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

PubMed

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

2009-10-01

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

Ultra-fast bright field and fluorescence imaging of the dynamics of micrometer-sized objects

NASA Astrophysics Data System (ADS)

Chen, Xucai; Wang, Jianjun; Versluis, Michel; de Jong, Nico; Villanueva, Flordeliza S.

2013-06-01

High speed imaging has application in a wide area of industry and scientific research. In medical research, high speed imaging has the potential to reveal insight into mechanisms of action of various therapeutic interventions. Examples include ultrasound assisted thrombolysis, drug delivery, and gene therapy. Visual observation of the ultrasound, microbubble, and biological cell interaction may help the understanding of the dynamic behavior of microbubbles and may eventually lead to better design of such delivery systems. We present the development of a high speed bright field and fluorescence imaging system that incorporates external mechanical waves such as ultrasound. Through collaborative design and contract manufacturing, a high speed imaging system has been successfully developed at the University of Pittsburgh Medical Center. We named the system "UPMC Cam," to refer to the integrated imaging system that includes the multi-frame camera and its unique software control, the customized modular microscope, the customized laser delivery system, its auxiliary ultrasound generator, and the combined ultrasound and optical imaging chamber for in vitro and in vivo observations. This system is capable of imaging microscopic bright field and fluorescence movies at 25 × 106 frames per second for 128 frames, with a frame size of 920 × 616 pixels. Example images of microbubble under ultrasound are shown to demonstrate the potential application of the system.

Ultra-fast bright field and fluorescence imaging of the dynamics of micrometer-sized objects

PubMed Central

Chen, Xucai; Wang, Jianjun; Versluis, Michel; de Jong, Nico; Villanueva, Flordeliza S.

2013-01-01

High speed imaging has application in a wide area of industry and scientific research. In medical research, high speed imaging has the potential to reveal insight into mechanisms of action of various therapeutic interventions. Examples include ultrasound assisted thrombolysis, drug delivery, and gene therapy. Visual observation of the ultrasound, microbubble, and biological cell interaction may help the understanding of the dynamic behavior of microbubbles and may eventually lead to better design of such delivery systems. We present the development of a high speed bright field and fluorescence imaging system that incorporates external mechanical waves such as ultrasound. Through collaborative design and contract manufacturing, a high speed imaging system has been successfully developed at the University of Pittsburgh Medical Center. We named the system “UPMC Cam,” to refer to the integrated imaging system that includes the multi-frame camera and its unique software control, the customized modular microscope, the customized laser delivery system, its auxiliary ultrasound generator, and the combined ultrasound and optical imaging chamber for in vitro and in vivo observations. This system is capable of imaging microscopic bright field and fluorescence movies at 25 × 106 frames per second for 128 frames, with a frame size of 920 × 616 pixels. Example images of microbubble under ultrasound are shown to demonstrate the potential application of the system. PMID:23822346

Strategies for Controlled Delivery of Growth Factors and Cells for Bone Regeneration

PubMed Central

Vo, Tiffany N.; Kasper, F. Kurtis; Mikos, Antonios G.

2012-01-01

The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with preprogrammed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering. PMID:22342771

Optimisation of a two-liquid component pre-filled acrylic bone cement system: a design of experiments approach to optimise cement final properties.

PubMed

Clements, James; Walker, Gavin; Pentlavalli, Sreekanth; Dunne, Nicholas

2014-10-01

The initial composition of acrylic bone cement along with the mixing and delivery technique used can influence its final properties and therefore its clinical success in vivo. The polymerisation of acrylic bone cement is complex with a number of processes happening simultaneously. Acrylic bone cement mixing and delivery systems have undergone several design changes in their advancement, although the cement constituents themselves have remained unchanged since they were first used. This study was conducted to determine the factors that had the greatest effect on the final properties of acrylic bone cement using a pre-filled bone cement mixing and delivery system. A design of experiments (DoE) approach was used to determine the impact of the factors associated with this mixing and delivery method on the final properties of the cement produced. The DoE illustrated that all factors present within this study had a significant impact on the final properties of the cement. An optimum cement composition was hypothesised and tested. This optimum recipe produced cement with final mechanical and thermal properties within the clinical guidelines and stated by ISO 5833 (International Standard Organisation (ISO), International standard 5833: implants for surgery-acrylic resin cements, 2002), however the low setting times observed would not be clinically viable and could result in complications during the surgical technique. As a result further development would be required to improve the setting time of the cement in order for it to be deemed suitable for use in total joint replacement surgery.

Does the Discourse of Employer Linked Charter Schools Signal a Commitment to Work Force Development or Transformational Learning?

ERIC Educational Resources Information Center

Freeman, Eric; Lakes, Richard D.

2005-01-01

The latest model for educational reform emerging in the US vocational-technical delivery system is the employer linked charter school (ELCS). This emerging concept is viewed as a partnership between constituents in the regular school organization and employers who are directly involved in the school's design, governance, and delivery of learning…

Structural Design and Analysis of Un-pressurized Cargo Delivery Vehicle

NASA Technical Reports Server (NTRS)

Martinovic, Zoran N.

2007-01-01

As part of the Exploration Systems Architecture Study, NASA has defined a family of vehicles to support lunar exploration and International Space Station (ISS) re-supply missions after the Shuttle s retirement. The Un-pressurized Cargo Delivery Vehicle (UCDV) has been envisioned to be an expendable logistics delivery vehicle that would be used to deliver external cargo to the ISS. It would be launched on the Crew Launch Vehicle and would replace the Crew Exploration Vehicle. The estimated cargo would be the weight of external logistics to the ISS. Determining the minimum weight design of the UCDV during conceptual design is the major issue addressed in this paper. This task was accomplished using a procedure for rapid weight estimation that was based on Finite Element Analysis and sizing of the vehicle by the use of commercially available codes. Three design concepts were analyzed and their respective weights were compared. The analytical structural weight was increased by a factor to account for structural elements that were not modeled. Significant reduction in weight of a composite design over metallic was achieved for similar panel concepts.

Meeting patient expectations: healthcare professionals and service re-engineering.

PubMed

Laing, Angus

2002-08-01

A central theme underpinning the reform of healthcare systems in western economies since the 1980s has been the emphasis on reorienting service provision around the patient. Healthcare organizations have been forced to re-appraise the design of the service delivery process, specifically the service encounter, to take account of these changing patient expectations. This reorientation of healthcare services around the patient has fundamental implications for healthcare professionals, specifically challenging the dominance of service professionals in the design and delivery of health services. Utilizing a qualitative methodological framework, this paper explores the responses of healthcare professionals to service redesign initiatives implemented in acute NHS hospitals in Scotland and considers the implications of such professional responses for the development of patient-focused service delivery. Within this, it specifically examines evolving professional perspectives on the place of a service user focus in a publicly funded healthcare system, professional attitudes towards private sector managerial practices, and the dynamics of changing professional behaviour.

Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs.

PubMed

Dahan, Arik; Hoffman, Amnon

2008-07-02

As a consequence of modern drug discovery techniques, there has been a consistent increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble. A great challenge facing the pharmaceutical scientist is making these molecules into orally administered medications with sufficient bioavailability. One of the most popular approaches to improve the oral bioavailability of these molecules is the utilization of a lipid based drug delivery system. Unfortunately, current development strategies in the area of lipid based delivery systems are mostly empirical. Hence, there is a need for a simplified in vitro method to guide the selection of a suitable lipidic vehicle composition and to rationalize the delivery system design. To address this need, a dynamic in vitro lipolysis model, which provides a very good simulation of the in vivo lipid digestion process, has been developed over the past few years. This model has been extensively used for in vitro assessment of different lipid based delivery systems, leading to enhanced understanding of the suitability of different lipids and surfactants as a delivery system for a given poorly water soluble drug candidate. A key goal in the development of the dynamic in vitro lipolysis model has been correlating the in vitro data of various drug-lipidic delivery system combinations to the resultant in vivo drug profile. In this paper, we discuss and review the need for this model, its underlying theory, practice and limitations, and the available data accumulated in the literature. Overall, the dynamic in vitro lipolysis model seems to provide highly useful initial guidelines in the development process of oral lipid based drug delivery systems for poorly water soluble drugs, and it predicts phenomena that occur in the pre-enterocyte stages of the intestinal absorption cascade.

Pluronic® F-127 and Pluronic Lecithin Organogel (PLO): main features and their applications in topical and transdermal administration of drugs.

PubMed

Almeida, Hugo; Amaral, Maria Helena; Lobão, Paulo; Lobo, José Manuel Sousa

2012-01-01

Topical drug treatment aims at providing high concentrations of drugs at the site of application so as to avoid adverse systemic effects associated with oral administration. Smart polymers, or stimuli-responsive polymers, are able to respond to a stimulus by showing physical or chemical changes in their behaviour as, for example, the delivery of the drug carried by them. The thermo-responsive nature of Pluronic® F-127 (Basf, Ludwigshafen, Germany) makes it an excellent candidate for the delivery of drugs at various application sites. In recent years, PF-127, and later, Pluronic lecithin organogels (PLO), have attracted particular interest in the design of dermal and transdermal delivery systems with a view to promoting, improving or retarding drug permeation through the skin, bearing in mind that for topical delivery systems, accumulation in the skin with minimal permeation is desired, while for systemic delivery, the opposite behaviour is preferred. In this review, we discuss the properties and characteristics of PF-127 and Pluronic lecithin organogels (PLO), and present many examples and advantages of the application of these polymeric systems in topical and transdermal administration of drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Computational design and multiscale modeling of a nanoactuator using DNA actuation.

PubMed

Hamdi, Mustapha

2009-12-02

Developments in the field of nanobiodevices coupling nanostructures and biological components are of great interest in medical nanorobotics. As the fundamentals of bio/non-bio interaction processes are still poorly understood in the design of these devices, design tools and multiscale dynamics modeling approaches are necessary at the fabrication pre-project stage. This paper proposes a new concept of optimized carbon nanotube based servomotor design for drug delivery and biomolecular transport applications. The design of an encapsulated DNA-multi-walled carbon nanotube actuator is prototyped using multiscale modeling. The system is parametrized by using a quantum level approach and characterized by using a molecular dynamics simulation. Based on the analysis of the simulation results, a servo nanoactuator using ionic current feedback is simulated and analyzed for application as a drug delivery carrier.

Building Student and Family-Centered Care Coordination Through Ongoing Delivery System Design.

PubMed

Baker, Dian; Anderson, Lori; Johnson, Jody

2017-01-01

In 2016 the National Association of School Nurses released an updated framework for school nurse practice. One highlight of the new framework is 21st century care coordination. That is, moving beyond basic case management to a systems-level approach for delivery of school health services. The framework broadly applies the term care coordination to include direct care and communication across systems. School nurses are often engaged in efforts to create school health care homes that serve as an axis of coordination for students and families between primary care offices and the schools. Effective care coordination requires that the school nurses not only know the principles of traditional case management but also understand complex systems that drive effective care coordination. The outcome of a system-level approach is enhanced access to services in an integrated health care delivery system that includes the school nurse as an integral member of the school's health care team. This article presents a comprehensive, system-level model of care coordination for school nurse leadership and practice.

48 CFR 42.302 - Contract administration functions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... delivery schedules. (32) Perform preaward surveys (see Subpart 9.1). (33) Advise and assist contractors... performance in the areas of design, development, and production. (41) Evaluate for adequacy and perform surveillance of contractor engineering efforts and management systems that relate to design, development...

A Case Study of Online Degree Course Design and Performance of Online Learners

ERIC Educational Resources Information Center

Saul, Robert

2013-01-01

The increasing demand of learners in online higher education courses currently presents a challenge to online course designs in increasing the performance of learners. The online course design process involves many challenges, including a new delivery system, understanding online drivers for success, and an emerging profession of online…

Design, Delivery and Evaluation of Teaching by Service Users and Carers

ERIC Educational Resources Information Center

Benbow, Susan Mary; Taylor, Louise; Mustafa, Nageen; Morgan, Kathleen

2011-01-01

Education influences individual health and social care professionals and the systems in which they work. We describe a postgraduate educational program that did this through involving service users and carers in designing and facilitating teaching programs. A module of teaching was designed and delivered in partnership with users and carers from…

How to Tackle Tough Facility Design Considerations

ERIC Educational Resources Information Center

Kalina, David

2007-01-01

This article is part of a series that has offered insight on planning a facilities project, hiring professionals, delivery system options and owner's responsibilities. In this article, the author focuses on some of the planning and design concepts one may be asked to consider in providing direction to his design and construction team. These…

Buccoadhesive drug delivery systems--extensive review on recent patents.

PubMed

Pathan, Shadab A; Iqbal, Zeenat; Sahani, Jasjeet K; Talegaonkar, Sushma; Khar, Roop K; Ahmad, Farhan J

2008-01-01

Peroral administration of drugs, although most preferred by both clinicians and patients has several disadvantages such as hepatic first pass metabolism and enzymatic degradation within the GI tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for administration of these drugs. Among the various transmucosal routes studied the buccal mucosa offers several advantages for controlled drug delivery for extended period of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract is avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form, design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is thus a promising area for continued research with the aim of systemic and local delivery of orally inefficient drugs as well as feasible and attractive alternative for non-invasive delivery of potent protein and peptide drug molecules. Extensive review pertaining specifically to the patents relating to buccal drug delivery is currently available. However, many patents e.g. US patents 6, 585,997; US20030059376A1 etc. have been mentioned in few articles. It is the objective of this article to extensively review buccal drug delivery by discussing the recent patents available. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems.

MessageSpace: a messaging system for health research

NASA Astrophysics Data System (ADS)

Escobar, Rodrigo D.; Akopian, David; Parra-Medina, Deborah; Esparza, Laura

2013-03-01

Mobile Health (mHealth) has emerged as a promising direction for delivery of healthcare services via mobile communication devices such as cell phones. Examples include texting-based interventions for chronic disease monitoring, diabetes management, control of hypertension, smoking cessation, monitoring medication adherence, appointment keeping and medical test result delivery; as well as improving patient-provider communication, health information communication, data collection and access to health records. While existing messaging systems very well support bulk messaging and some polling applications, they are not designed for data collection and processing of health research oriented studies. For that reason known studies based on text-messaging campaigns have been constrained in participant numbers. In order to empower healthcare promotion and education research, this paper presents a system dedicated for healthcare research. It is designed for convenient communication with various study groups, feedback collection and automated processing.

Microneedles for intradermal and transdermal delivery

PubMed Central

Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

2014-01-01

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

Mucosal delivery of liposome-chitosan nanoparticle complexes.

PubMed

Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

2009-01-01

Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

Targeted delivery of drugs for liver fibrosis.

PubMed

Li, Feng; Wang, Ji-yao

2009-05-01

Liver fibrosis and its end stage disease cirrhosis are a major cause of mortality and morbidity around the world. There is no effective pharmaceutical intervention for liver fibrosis at present. Many drugs that show potent antifibrotic activities in vitro often show only minor effects in vivo because of insufficient concentrations of drugs accumulating around the target cell and their adverse effects as a result of affecting other non-target cells. Hepatic stellate cells (HSC) play a critical role in the fibrogenesis of liver, so they are the target cells of antifibrotic therapy. Several kinds of targeted delivery system that could target the receptors expressed on HSC have been designed, and have shown an attractive targeted potential in vivo. After being carried by these delivery systems, many agents showed a powerful antifibrotic effect in animal models of liver fibrosis. These targeted delivery systems provide a new pathway for the therapy of liver fibrosis. The characteristics of theses targeted carriers are reviewed in this paper.

Exploration of the Performance of a Hybrid Closed Loop Insulin Delivery Algorithm That Includes Insulin Delivery Limits Designed to Protect Against Hypoglycemia.

PubMed

de Bock, Martin; Dart, Julie; Roy, Anirban; Davey, Raymond; Soon, Wayne; Berthold, Carolyn; Retterath, Adam; Grosman, Benyamin; Kurtz, Natalie; Davis, Elizabeth; Jones, Timothy

2017-01-01

Hypoglycemia remains a risk for closed loop insulin delivery particularly following exercise or if the glucose sensor is inaccurate. The aim of this study was to test whether an algorithm that includes a limit to insulin delivery is effective at protecting against hypoglycemia under those circumstances. An observational study on 8 participants with type 1 diabetes was conducted, where a hybrid closed loop system (HCL) (Medtronic™ 670G) was challenged with hypoglycemic stimuli: exercise and an overreading glucose sensor. There was no overnight or exercise-induced hypoglycemia during HCL insulin delivery. All daytime hypoglycemia was attributable to postmeal bolused insulin in those participants with a more aggressive carbohydrate factor. HCL systems rely on accurate carbohydrate ratios and carbohydrate counting to avoid hypoglycemia. The algorithm that was tested against moderate exercise and an overreading glucose sensor performed well in terms of hypoglycemia avoidance. Algorithm refinement continues in preparation for long-term outpatient trials.

Biocompatibility of Chitosan Carriers with Application in Drug Delivery

PubMed Central

Rodrigues, Susana; Dionísio, Marita; Remuñán López, Carmen; Grenha, Ana

2012-01-01

Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. PMID:24955636

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

PubMed

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

2012-10-01

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

Design and mechanistic study of a novel gold nanocluster-based drug delivery system.

PubMed

Li, Qinzhen; Pan, Yiting; Chen, Tiankai; Du, Yuanxin; Ge, Honghua; Zhang, Buchang; Xie, Jianping; Yu, Haizhu; Zhu, Manzhou

2018-05-22

Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self-regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide. The Van-loaded Au NCs show comparable antimicrobial activity with Van on its own, and the number of Van released by the Pep-Au NCs is found to be proportional to the amount of bacteria present. The controlled nature of the Van release is very encouraging, and predominantly due to the stronger binding affinity of Van with bacteria than that with Au NCs. In addition, these fluorescent Au NCs could also be used to construct temperature sensors, which enable the in vitro and in vivo bioimaging.

Applying Toyota production system techniques for medication delivery: improving hospital safety and efficiency.

PubMed

Newell, Terry L; Steinmetz-Malato, Laura L; Van Dyke, Deborah L

2011-01-01

The inpatient medication delivery system used at a large regional acute care hospital in the Midwest had become antiquated and inefficient. The existing 24-hr medication cart-fill exchange process with delivery to the patients' bedside did not always provide ordered medications to the nursing units when they were needed. In 2007 the principles of the Toyota Production System (TPS) were applied to the system. Project objectives were to improve medication safety and reduce the time needed for nurses to retrieve patient medications. A multidisciplinary team was formed that included representatives from nursing, pharmacy, informatics, quality, and various operational support departments. Team members were educated and trained in the tools and techniques of TPS, and then designed and implemented a new pull system benchmarking the TPS Ideal State model. The newly installed process, providing just-in-time medication availability, has measurably improved delivery processes as well as patient safety and satisfaction. Other positive outcomes have included improved nursing satisfaction, reduced nursing wait time for delivered medications, and improved efficiency in the pharmacy. After a successful pilot on two nursing units, the system is being extended to the rest of the hospital. © 2010 National Association for Healthcare Quality.

ENHANCED PRACTICAL PHOTOSYNTHETIC CO2 MITIGATION

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

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

2001-10-15

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

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

NASA Astrophysics Data System (ADS)

Etame, Arnold B.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non-transport permissive and intact BBB, we also assessed the role of magnetic resonance imaging (MRI) guided focused ultrasound (MRgFUS) disruption of the BBB in enhancing permeation of AuNPs across the intact BBB and tumor BBB in vivo. MRgFUS is a novel technique that can transiently increase BBB permeability thereby allowing delivery of therapeutics into the CNS. We demonstrated enhanced delivery of AuNPs with therapeutic potential into the CNS via MRgFUS. Our study was the first to establish a definitive role for MRgFUS in delivering AuNPs into the CNS. In summary, this thesis describes results from a series of research projects that have contributed to our understanding of the influence of design features on AuNP permeation through the BBB and also the potential role of MRgFUS in AuNP permeation across the BBB.

Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review

PubMed Central

Bose, Susmita; Tarafder, Solaiman

2012-01-01

Calcium phosphates (CaPs) are the most widely used bone substitutes in bone tissue engineering due to their compositional similarities to bone mineral and excellent biocompatibility. In recent years, CaPs, especially hydroxyapatite and tricalcium phosphate, have attracted significant interest in simultaneous use as bone substitute and drug delivery vehicle, adding a new dimension to their application. CaPs are more biocompatible than many other ceramic and inorganic nanoparticles. Their biocompatibility and variable stoichiometry, thus surface charge density, functionality, and dissolution properties, make them suitable for both drug and growth factor delivery. CaP matrices and scaffolds have been reported to act as delivery vehicles for growth factors and drugs in bone tissue engineering. Local drug delivery in musculoskeletal disorder treatments can address some of the critical issues more effectively and efficiently than the systemic delivery. CaPs are used as coatings on metallic implants, CaP cements, and custom designed scaffolds to treat musculoskeletal disorders. This review highlights some of the current drug and growth factor delivery approaches and critical issues using CaP particles, coatings, cements, and scaffolds towards orthopedic and dental applications. PMID:22127225

Solving Disparities Through Payment And Delivery System Reform: A Program To Achieve Health Equity.

PubMed

DeMeester, Rachel H; Xu, Lucy J; Nocon, Robert S; Cook, Scott C; Ducas, Andrea M; Chin, Marshall H

2017-06-01

Payment systems generally do not directly encourage or support the reduction of health disparities. In 2013 the Finding Answers: Solving Disparities through Payment and Delivery System Reform program of the Robert Wood Johnson Foundation sought to understand how alternative payment models might intentionally incorporate a disparities-reduction component to promote health equity. A qualitative analysis of forty proposals to the program revealed that applicants generally did not link payment reform tightly to disparities reduction. Most proposed general pay-for-performance, global payment, or shared savings plans, combined with multicomponent system interventions. None of the applicants proposed making any financial payments contingent on having successfully reduced disparities. Most applicants did not address how they would optimize providers' intrinsic and extrinsic motivation to reduce disparities. A better understanding of how payment and care delivery models might be designed and implemented to reduce health disparities is essential. Project HOPE—The People-to-People Health Foundation, Inc.

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

NASA Technical Reports Server (NTRS)

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

1994-01-01

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

Targeted Immunomodulation Using Antigen-Conjugated Nanoparticles

PubMed Central

McCarthy, Derrick P.; Hunter, Zoe N.; Chackerian, Bryce; Shea, Lonnie D.; Miller, Stephen D.

2014-01-01

The growing prevalence of nanotechnology in the fields of biology, medicine and the pharmaceutical industry is confounded by the relatively small amount of data on the impact of these materials on the immune system. In addition to concerns surrounding the potential toxicity of nanoparticle (NP)-based delivery systems, there is also a demand for a better understanding of the mechanisms governing interactions of NPs with the immune system. Nanoparticles can be tailored to suppress, enhance, or subvert recognition by the immune system. This “targeted immunomodulation” can be achieved by delivery of unmodified particles, or by modifying particles to deliver drugs, proteins/peptides or genes to a specific site. In order to elicit the desired, beneficial immune response, considerations should be made at every step of the design process: the NP platform itself, ligands and other modifiers, the delivery route, and the immune cells that will encounter the conjugated NPs can all impact host immune responses. PMID:24616452

Design and Concept of Polyzwitterionic Copolymer Microgel Drug Delivery Systems In Situ Loaded with Non-steroidal Anti-inflammatory Ibuprofen.

PubMed

Kostova, Bistra; Kamenska, Elena; Georgieva, Dilyana; Balashev, Konstantin; Rachev, Dimitar; Georgiev, George

2017-01-01

Nowadays, the modern pharmaceutical investigations are directed toward obtaining of new polymer micro- and nano-sized drug delivery carriers. In this respect, the use of hydrogel carriers based on polyzwitterions (PZIs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of micro-structured p(VA-co-DMAPS) systems with different compositions in situ loaded with Ibuprofen by emulsifier-free emulsion copolymerization (EEC) in water. The mean size of the prepared microparticles was measured by SEM and particles have been visualized by AFM. The inclusion of Ibuprofen in the polyzwitterionic copolymer microgel systems was established by using DSC. In vitro drug release experiments were carried out in order to estimate the ability of the obtained microgels to modify the release of water-insoluble Ibuprofen.

Recent progress on nanoparticle-based drug delivery systems for cancer therapy

PubMed Central

Xin, Yanru; Yin, Mingming; Zhao, Liyuan; Meng, Fanling; Luo, Liang

2017-01-01

The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years. PMID:28884040

Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine

PubMed Central

Nguyen, Minh Khanh; Alsberg, Eben

2014-01-01

Polymer hydrogels have been widely explored as therapeutic delivery matrices because of their ability to present sustained, localized and controlled release of bioactive factors. Bioactive factor delivery from injectable biopolymer hydrogels provides a versatile approach to treat a wide variety of diseases, to direct cell function and to enhance tissue regeneration. The innovative development and modification of both natural-(e.g., alginate (ALG), chitosan, hyaluronic acid (HA), gelatin, heparin (HEP), etc.) and synthetic-(e.g., polyesters, polyethyleneimine (PEI), etc.) based polymers has resulted in a variety of approaches to design drug delivery hydrogel systems from which loaded therapeutics are released. This review presents the state-of-the-art in a wide range of hydrogels that are formed though self-assembly of polymers and peptides, chemical crosslinking, ionic crosslinking and biomolecule recognition. Hydrogel design for bioactive factor delivery is the focus of the first section. The second section then thoroughly discusses release strategies of payloads from hydrogels for therapeutic medicine, such as physical incorporation, covalent tethering, affinity interactions, on demand release and/or use of hybrid polymer scaffolds, with an emphasis on the last 5 years. PMID:25242831

Advancements in the oral delivery of Docetaxel: challenges, current state-of-the-art and future trends

PubMed Central

Sohail, Muhammad Farhan; Rehman, Mubashar; Sarwar, Hafiz Shoaib; Naveed, Sara; Salman, Omer; Bukhari, Nadeem Irfan; Hussain, Irshad; Webster, Thomas J; Shahnaz, Gul

2018-01-01

The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research. PMID:29922053

Advancements in the oral delivery of Docetaxel: challenges, current state-of-the-art and future trends.

PubMed

Sohail, Muhammad Farhan; Rehman, Mubashar; Sarwar, Hafiz Shoaib; Naveed, Sara; Salman, Omer; Bukhari, Nadeem Irfan; Hussain, Irshad; Webster, Thomas J; Shahnaz, Gul

2018-01-01

The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research.

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

PubMed

Meng, Jianing; Agrahari, Vivek; Youm, Ibrahima

2017-03-01

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

Disease-responsive drug delivery: the next generation of smart delivery devices.

PubMed

Wanakule, Prinda; Roy, Krishnendu

2012-01-01

With the advent of highly potent and cytotoxic drugs, it is increasingly critical that they be targeted and released only in cells of diseased tissues, while sparing physiologically normal neighbors. Simple ligand-based targeting of drug carriers, although promising, cannot always provide the required specificity to achieve this since often normal cells also express significant levels of the targeted receptors. Therefore, stimuli-responsive delivery systems are being explored to allow drug release from nano- and microcarriers and implantable devices, primarily in the presence of physiological or disease-specific pathophysiological signals. Designing smart biomaterials that respond to temperature or pH changes, protein and ligand binding, disease-specific degradation, e.g. enzymatic cleavage, has become an integral part of this approach. These strategies are used in combination with nano- and microparticle systems to improve delivery efficiency through several routes of administration, and with injectable or implantable systems for long term controlled release. This review focuses on recent developments in stimuli-responsive systems, their physicochemical properties, release profiles, efficacy, safety and biocompatibility, as well as future perspectives.

Ultralow-power electronics for biomedical applications.

PubMed

Chandrakasan, Anantha P; Verma, Naveen; Daly, Denis C

2008-01-01

The electronics of a general biomedical device consist of energy delivery, analog-to-digital conversion, signal processing, and communication subsystems. Each of these blocks must be designed for minimum energy consumption. Specific design techniques, such as aggressive voltage scaling, dynamic power-performance management, and energy-efficient signaling, must be employed to adhere to the stringent energy constraint. The constraint itself is set by the energy source, so energy harvesting holds tremendous promise toward enabling sophisticated systems without straining user lifestyle. Further, once harvested, efficient delivery of the low-energy levels, as well as robust operation in the aggressive low-power modes, requires careful understanding and treatment of the specific design limitations that dominate this realm. We outline the performance and power constraints of biomedical devices, and present circuit techniques to achieve complete systems operating down to power levels of microwatts. In all cases, approaches that leverage advanced technology trends are emphasized.

48 CFR 47.303-15 - F.o.b. designated air carrier's terminal, point of exportation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false F.o.b. designated air... Contracts 47.303-15 F.o.b. designated air carrier's terminal, point of exportation. (a) Explanation of delivery term. F.o.b. designated air carrier's terminal, point of exportation means free of expense to the...

48 CFR 47.303-16 - F.o.b. designated air carrier's terminal, point of importation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false F.o.b. designated air... Contracts 47.303-16 F.o.b. designated air carrier's terminal, point of importation. (a) Explanation of delivery term. F.o.b. designated air carrier's terminal, point of importation means free of expense to the...

Development of New Transportation/Storage Cask System for Use by DOE Russian Research Reactor Fuel Return Program

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

Michael Tyacke; Frantisek Svitak; Jiri Rychecky

2010-04-01

The United States, the Russian Federation, and the International Atomic Energy Agency (IAEA) have been working together on a program called the Russian Research Reactor Fuel Return (RRRFR) Program. The purpose of this program is to return Soviet or Russian supplied high-enriched uranium (HEU) fuel currently stored at Russian-designed research reactors throughout the world to Russia. To accommodate transport of the HEU spent nuclear fuel (SNF), a new large-capacity transport/storage cask system was specially designed for handling and operations under the unique conditions for these research reactor facilities. This new cask system is named the ŠKODA VPVR/M cask. The design,more » licensing, testing, and delivery of this new cask system are the results of a significant international cooperative effort by several countries and involved numerous private and governmental organizations. This paper contains the following sections: (1) Introduction/Background; (2) VPVR/M Cask Description; (3) Ancillary Equipment, (4) Cask Licensing; (5) Cask Demonstration and Operations; (6) IAEA Procurement, Quality Assurance Inspections, Fabrication, and Delivery; and, (7) Summary and Conclusions.« less

Development of a New Transportation/Storage Cask System for Use by the DOE Russian Research Reactor Fuel Return Program

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

Michael J. Tyacke; Frantisek Svitak; Jiri Rychecky

2007-10-01

The United States, the Russian Federation, and the International Atomic Energy Agency (IAEA) have been working together on a program called the Russian Research Reactor Fuel Return (RRRFR) Program. The purpose of this program is to return Soviet or Russian-supplied high-enriched uranium (HEU) fuel, currently stored at Russian-designed research reactors throughout the world, to Russia. To accommodate transport of the HEU spent nuclear fuel (SNF), a new large-capacity transport/storage cask system was specially designed for handling and operations under the unique conditions at these research reactor facilities. This new cask system is named the ŠKODA VPVR/M cask. The design, licensing,more » testing, and delivery of this new cask system result from a significant international cooperative effort by several countries and involved numerous private and governmental organizations. This paper contains the following sections: 1) Introduction; 2) VPVR/M Cask Description; 3) Ancillary Equipment, 4) Cask Licensing; 5) Cask Demonstration and Operations; 6) IAEA Procurement, Quality Assurance Inspections, Fabrication, and Delivery; and, 7) Conclusions.« less

CEO summit. The new delivery & financing realities. Part III of III.

PubMed

Becker, B F; Cramer, H; Easley, D; Nathanson, P; Neeson, R; Raney, J; Samuelson, C; Ummel, S

1994-08-20

In cooperation with McManis Associates Inc., Washington, Hospitals & Health Networks recently convened a summit on the integration of financing and delivery in health care. This installment is the third of a three-part series on lessons learned by those on the front lines of integration activity. The session was designed and facilitated by senior associates at McManis. Among the issues summit participants discussed in the second segment: What level of understanding do purchasers have of the factors that differentiate quality in health care services? Can provider-driven integrated delivery systems compete with insurer-driven ones? And what happens when a large integrated delivery system merges with a dominant insurer, as happened in the Philadelphia market? Can that model be successfully replicated in other markets? In this final segment, participants talk about whether providers' deep connections to their communities will add value in a reformed delivery system; how incentives might be aligned among all the players in integrated networks and organizations; how the concept of community focus might be redefined under systems integration; and the process involved in preparing for constant, accelerated change. The second segment concluded with comments about the assets providers and insurers bring to integrated health systems, and whether the merger experience of Graduate Health System and QCC/Independence Blue Cross could be replicated in other markets or not.

Academic Institutionalization of Community Health Services: Way Ahead in Medical Education Reforms

PubMed Central

Kumar, Raman

2012-01-01

Policy on medical education has a major bearing on the outcome of health care delivery system. Countries plan and execute development of human resource in health, based on the realistic assessments of health system needs. A closer observation of medical education and its impact on the delivery system in India reveals disturbing trends. Primary care forms backbone of any system for health care delivery. One of the major challenges in India has been chronic deficiency of trained human resource eager to work in primary care setting. Attracting talent and employing skilled workforce seems a distant dream. Talking specifically of the medical education, there are large regional variations, urban - rural divide and issues with financing of the infrastructure. The existing design of medical education is not compatible with the health care delivery system of India. Impact is visible at both qualitative as well as quantitative levels. Medical education and the delivery system are working independent of each other, leading outcomes which are inequitable and unjust. Decades of negligence of medical education regulatory mechanism has allowed cropping of multiple monopolies governed by complex set of conflict of interest. Primary care physicians, supposed to be the community based team leaders stand disfranchised academically and professionally. To undo the distorted trajectory, a paradigm shift is required. In this paper, we propose expansion of ownership in medical education with academic institutionalization of community health services. PMID:24478994

GIS Learning Objects: An Approach to Content Aggregation

ERIC Educational Resources Information Center

Govorov, Michael; Gienko, Gennady

2013-01-01

Content development and maintenance of geographic information systems (GIS) related courses, especially designed for distance and online delivery, could be a tedious task even for an experienced instructor. The paper outlines application of abstract instructional design techniques for modeling course structure and developing corresponding course…

Digital Audio: A Sound Design Element.

ERIC Educational Resources Information Center

Barron, Ann; Varnadoe, Susan

1992-01-01

Discussion of incorporating audio into videodiscs for multimedia educational applications highlights a project developed for the Navy that used digital audio in an interactive video delivery system (IVDS) for training sonar operators. Storage constraints with videodiscs are explained, design requirements for the IVDS are described, and production…

Recommended guide for next generation of transportation design build procurement and contracting in the state of Georgia.

DOT National Transportation Integrated Search

2012-09-01

The overall objective of this research project is to develop a systematic approach that evaluates the appropriateness of Design Build Project Delivery System for a transportation project. State DOTs can benefit from this systematic assessment approac...

Nanostructure-mediated drug delivery.

PubMed

Hughes, Gareth A

2005-03-01

Nanotechnology is expected to have an impact on all industries including semiconductors, manufacturing, and biotechnology. Tools that provide the capability to characterize and manipulate materials at the nanoscale level further elucidate nanoscale phenomena and equip researchers and developers with the ability to fabricate novel materials and structures. One of the most promising societal impacts of nanotechnology is in the area of nanomedicine. Personalized health care, rational drug design, and targeted drug delivery are some of the benefits of a nanomedicine-based approach to therapy. This review will focus on the development of nanoscale drug delivery mechanisms. Nanostructured drug carriers allow for the delivery of not only small-molecule drugs but also the delivery of nucleic acids and proteins. Delivery of these molecules to specific areas within the body can be achieved, which will reduce systemic side effects and allow for more efficient use of the drug.

Arrow 227: Air transport system design simulation

NASA Technical Reports Server (NTRS)

Bontempi, Michael; Bose, Dave; Brophy, Georgeann; Cashin, Timothy; Kanarios, Michael; Ryan, Steve; Peterson, Timothy

1992-01-01

The Arrow 227 is a student-designed commercial transport for use in a overnight package delivery network. The major goal of the concept was to provide the delivery service with the greatest potential return on investment. The design objectives of the Arrow 227 were based on three parameters; production cost, payload weight, and aerodynamic efficiency. Low production cost helps to reduce initial investment. Increased payload weight allows for a decrease in flight cycles and, therefore, less fuel consumption than an aircraft carrying less payload weight and requiring more flight cycles. In addition, fewer flight cycles will allow a fleet to last longer. Finally, increased aerodynamic efficiency in the form of high L/D will decrease fuel consumption.

Delivering Training for Highly Demanding Information Systems

ERIC Educational Resources Information Center

Norton, Andrew Lawrence; Coulson-Thomas, Yvette May; Coulson-Thomas, Colin Joseph; Ashurst, Colin

2012-01-01

Purpose: There is a lack of research covering the training requirements of organisations implementing highly demanding information systems (HDISs). The aim of this paper is to help in the understanding of appropriate training requirements for such systems. Design/methodology/approach: This research investigates the training delivery within a…

Exploring the role of peptides in polymer-based gene delivery.

PubMed

Sun, Yanping; Yang, Zhen; Wang, Chunxi; Yang, Tianzhi; Cai, Cuifang; Zhao, Xiaoyun; Yang, Li; Ding, Pingtian

2017-09-15

Polymers are widely studied as non-viral gene vectors because of their strong DNA binding ability, capacity to carry large payload, flexibility of chemical modifications, low immunogenicity, and facile processes for manufacturing. However, high cytotoxicity and low transfection efficiency substantially restrict their application in clinical trials. Incorporating functional peptides is a promising approach to address these issues. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we systematically summarize the role of peptides in polymer-based gene delivery, and elaborate how to rationally design polymer-peptide based gene delivery vectors. Polymers are widely studied as non-viral gene vectors, but suffer from high cytotoxicity and low transfection efficiency. Incorporating short, bioactive peptides into polymer-based gene delivery systems can address this issue. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we highlight the peptides' roles in polymer-based gene delivery, and elaborate how to utilize various functional peptides to enhance the transfection efficiency of polymers. The optimized peptide-polymer vectors should be able to alter their structures and functions according to biological microenvironments and utilize inherent intracellular pathways of cells, and consequently overcome the barriers during gene delivery to enhance transfection efficiency. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Programmed near-infrared light-responsive drug delivery system for combined magnetic tumor-targeting magnetic resonance imaging and chemo-phototherapy.

PubMed

Feng, Qianhua; Zhang, Yuanyuan; Zhang, Wanxia; Hao, Yongwei; Wang, Yongchao; Zhang, Hongling; Hou, Lin; Zhang, Zhenzhong

2017-02-01

In this study, an intelligent drug delivery system was developed by capping doxorubicin (DOX)-loaded hollow mesoporous CuS nanoparticles (HMCuS NPs) with superparamagnetic iron oxide nanoparticles (IONPs). Under near infrared (NIR) light irradiation, the versatile HMCuS NPs could exploit the merits of both photothermal therapy (PTT) and photodynamic therapy (PDT) simultaneously. Herein, the multifunctional IONPs as gatekeeper with the enhanced capping efficiency were supposed to realize "zero premature release" and minimize the adverse side effects during the drug delivery in vivo. More importantly, the hybrid metal nanoplatform (HMCuS/DOX@IONP-PEG) allowed several emerging exceptional characteristics. Our studies have substantiated the hybrid nanoparticles possessed an enhanced PTT effect due to coupled plasmonic resonances with an elevated heat-generating capacity. Notably, an effective removal of IONP-caps occurred after NIR-induced photo-hyperthermia via weakening of the coordination interactions between HMCuS-NH 2 and IONPs, which suggested the feasibility of sophisticated controlled on-demand drug release upon exposing to NIR stimulus with spatial/temporal resolution. Benefiting from the favorable magnetic tumor targeting efficacy, the in vitro and in vivo experiments indicated a remarkable anti-tumor therapeutic efficacy under NIR irradiation, resulting from the synergistic combination of chemo-phototherapy. In addition, T 2 -weighted magnetic resonance imaging (MRI) contrast performance of IONPs provided the identification of cancerous lesions. Based on these findings, the well-designed drug delivery system via integration of programmed functions will provide knowledge for advancing multimodality theranostic strategy. As we all know, a series of shortcomings of conventional chemotherapy such as limited stability, rapid clearing and non-specific tumor targeting ability remain a significant challenge to achieve successful clinical therapeutic efficiency in cancer treatments. Fortunately, developing drug delivery system under the assistance of multifunctional nanocarries might be a great idea. For the first time, we proposed an intelligent drug delivery system by capping DOX-loaded hollow mesoporous CuS nanoparticles (HMCuS NPs) with multifunctional IONPs to integrate programmed functions including enhanced PTT effect, sophisticated controlled drug release, magnetic targeting property and MR imaging. The results showed HMCuS/DOX@IONP-PEG could significantly enhance anti-tumor therapeutic efficacy due to the synergistic combination of chemo-phototherapy. By this delicate design, we believe such smart and extreme versatile all-in-one drug delivery platform could arouse broad interests in the fields of biomaterials, nanotechnology, and drug delivery system. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Implementing an Antibiotic Stewardship Information System to Improve Hospital Infection Control: A Co-Design Process.

PubMed

Maia, Mélanie R; Simões, Alexandra; Lapão, Luís V

2018-01-01

HAITooL information system design and implementation was based on Design Science Research Methodology, ensuring full participation, in close collaboration, of researchers and a multidisciplinary team of healthcare professionals. HAITooL enables effective monitoring of antibiotic resistance, antibiotic use and provides an antibiotic prescription decision-supporting system by clinicians, strengthening the patient safety procedures. The design, development and implementation process reveals benefits in organizational and behavior change with significant success. Leadership commitment multidisciplinary team and mainly informaticians engagement was crucial to the implementation process. Participants' motivation and the final product delivery and evolution depends on that.

Approaches to appropriate care delivery from a policy perspective: A case study of Australia, England and Switzerland.

PubMed

Robertson-Preidler, Joelle; Anstey, Matthew; Biller-Andorno, Nikola; Norrish, Alexandra

2017-07-01

Appropriateness is a conceptual way for health systems to balance Triple Aim priorities for improving population health, containing per capita cost, and improving the patient experience of care. Comparing system approaches to appropriate care delivery can help health systems establish priorities and facilitate appropriate care practices. We conceptualized system appropriateness by identifying policies that aim to achieve the Triple Aim and their consequent trade-offs for financing, clinical practice, and the individual patient. We used secondary data sources to compare the appropriate care approaches of Australia, England, and Switzerland according to financial, clinical, and individual appropriateness policies. Health system approaches to appropriate care delivery varied. England prioritizes public health, equity and efficiency at the expense of individual choice, while Switzerland focuses on individual patient preferences, but has higher per capita and out of pocket costs. Australia provides equity in public care access and private health care options that allows for more patient choice, with health care costs falling between the two. Integrating the Triple Aim into health system design and policy can facilitate appropriate care delivery at the system, clinical, and individual levels. Approaches will vary and require countries to negotiate and justify priorities and trade-offs within the context of thehealth system. Copyright © 2017 Elsevier B.V. All rights reserved.

Delivering safer immunotherapies for cancer

PubMed Central

Milling, Lauren; Zhang, Yuan; Irvine, Darrell J.

2017-01-01

Cancer immunotherapy is now a powerful clinical reality, with a steady progression of new drug approvals and a massive pipeline of additional treatments in clinical and preclinical development. However, modulation of the immune system can be a double-edged sword: Drugs that activate immune effectors are prone to serious non-specific systemic inflammation and autoimmune side effects. Drug delivery technologies have an important role to play in harnessing the power of immune therapeutics while avoiding on-target/off-tumor toxicities. Here we review mechanisms of toxicity for clinically-relevant immunotherapeutics, and discuss approaches based in drug delivery technology to enhance the safety and potency of these treatments. These include strategies to merge drug delivery with adoptive cellular therapies, targeting immunotherapies to tumors or select immune cells, and localizing therapeutics intratumorally. Rational design employing lessons learned from the drug delivery and nanomedicine fields has the potential to facilitate immunotherapy reaching its full potential. PMID:28545888

Preparing for an aging population and improving chronic disease management.

PubMed

Dexter, Paul R; Miller, Douglas K; Clark, Daniel O; Weiner, Michael; Harris, Lisa E; Livin, Lee; Myers, Isaac; Shaw, David; Blue, Lee Ann; Kunzer, John; Overhage, J Marc

2010-11-13

New models of health care delivery are inevitable. There is likely to be increasing emphasis on patient self-monitoring, health care delivery at patient homes, interdisciplinary treatment plans, a greater percentage of medical care delivered by non-physician health professionals, targeted health educational materials, and greater involvement and training of informal caregivers. The Information Technologies (IT) infrastructure of health systems will need to adapt. We have begun sorting out the implications of this future within a County public hospital system: defining the desirable features, relevant technologies, necessary modifications to the network, and additional data elements to be captured. We seek to build an infrastructure that will support new patient-focused technologies designed to more efficiently and effectively support older individuals. We hypothesize utility to further exploring the impact that new health care delivery models will have on health systems' IT infrastructures.

Solar heating and cooling systems design and development

NASA Technical Reports Server (NTRS)

1977-01-01

The development and delivery of eight prototype solar heating and cooling systems for installation and operational test was reported. Two heating and six heating and cooling units will be delivered for single family residences, multiple family residences and commercial applications.

Improving Health-care Delivery for Post-Traumatic Stress Disorder: An Interrelated Approach Leveraging Systems Engineering and Optimization

DTIC Science & Technology

2011-09-01

AND EXPERIMENTAL DESIGN ..........................................................................................................31   1...PRIMARY RESERCH QUESTION ............................................................41   C.   OBJECTIVE ACHIEVEMENT...Based Outpatient Clinic CPT Cognitive Processing Therapy DISE Distributed Information Systems Experimentation EBT Evidence-Based Treatment GMC

Nanobubbles: a promising efficient tool for therapeutic delivery.

PubMed

Cavalli, Roberta; Soster, Marco; Argenziano, Monica

2016-01-01

In recent decades ultrasound-guided delivery of drugs loaded on nanocarriers has been the focus of increasing attention to improve therapeutic treatments. Ultrasound has often been used in combination with microbubbles, micron-sized spherical gas-filled structures stabilized by a shell, to amplify the biophysical effects of the ultrasonic field. Nanometer size bubbles are defined nanobubbles. They were designed to obtain more efficient drug delivery systems. Indeed, their small sizes allow extravasation from blood vessels into surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Additionally, nanobubbles might be endowed with improved stability and longer residence time in systemic circulation. This review will describe the physico-chemical properties of nanobubbles, the formulation parameters and the drug loading approaches, besides potential applications as a therapeutic tool.

Persona Development and Educational Needs to Support Informal Caregivers.

PubMed

Al Awar, Zeina; Kuziemsky, Craig

2017-01-01

Informal caregivers are playing an increasing role in community based care delivery. Research is needed that looks at the educational needs of informal caregivers as a precursor to HIT design to support community care delivery. A challenge is informal caregivers have very diverse educational needs. Personas are an approach to describe user characteristics as part of systems design and this approach could be used to understand and categorize the various educational needs of informal caregivers. This paper addresses this research need and provides a method for persona development and the identification of educational needs for informal caregivers.

Meeting global health challenges through operational research and management science

PubMed Central

2011-01-01

Abstract This paper considers how operational research and management science can improve the design of health systems and the delivery of health care, particularly in low-resource settings. It identifies some gaps in the way operational research is typically used in global health and proposes steps to bridge them. It then outlines some analytical tools of operational research and management science and illustrates how their use can inform some typical design and delivery challenges in global health. The paper concludes by considering factors that will increase and improve the contribution of operational research and management science to global health. PMID:21897489

Meeting global health challenges through operational research and management science.

PubMed

Royston, Geoff

2011-09-01

This paper considers how operational research and management science can improve the design of health systems and the delivery of health care, particularly in low-resource settings. It identifies some gaps in the way operational research is typically used in global health and proposes steps to bridge them. It then outlines some analytical tools of operational research and management science and illustrates how their use can inform some typical design and delivery challenges in global health. The paper concludes by considering factors that will increase and improve the contribution of operational research and management science to global health.

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

NASA Astrophysics Data System (ADS)

Bue, Grant C.; Conger, Bruce S.

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

In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector

PubMed Central

Li, Yi; Beitelshees, Marie; Fang, Lei; Hill, Andrew; Ahmadi, Mahmoud Kamal; Chen, Mingfu; Davidson, Bruce A.; Knight, Paul; Smith, Randall J.; Andreadis, Stelios T.; Hakansson, Anders P.; Jones, Charles H.; Pfeifer, Blaine A.

2016-01-01

The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector. PMID:27419235

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

DTIC Science & Technology

2016-06-01

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

Day Care in Vermont: An Evaluation of the Vermont Model FAP Child Care Service System.

ERIC Educational Resources Information Center

Siedman, Eileen

This book presents an extensive examination of the organization and operation of the Vermont model day care delivery system which was designed in the context of the proposed Family Assistance Plan (FAP). The model tested the ability of Federal and State employees to work together and share resources in designing a new approach to welfare reform.…

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.

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

PubMed

Peppas, Nicholas A; Leobandung, William

2004-01-01

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

Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity.

PubMed

Tong, Xuwen; Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan

2016-10-01

In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunomodulatory properties of vitamins, flavonoids and plant oils and their potential as vaccine adjuvants and delivery systems.

PubMed

Vajdy, Michael

2011-11-01

During the past century, vaccinologists have attempted to mimic pathogens in their immune-enhancing capacity. This led to the development of life-saving vaccines based on live attenuated viruses, bacteria and toxoids. Hence, intense research in vaccine adjuvant discovery has focused on toll like receptors, mutant toxins and viral and bacterial vectors. Nutritive components such as vitamins and select polyphenols also possess immunomodulating properties without the potential toxic and adverse side effects of agents that mimic danger signals. This review pertains to immunomodulatory properties of nutritive components, that is vitamins A, C, D, E, flavonoids and plant oils, as potential vaccine adjuvants and delivery systems, covering Pubmed publication searches from 1980 through 2011. This relatively unexplored field of the potential of nutritive components as vaccine adjuvants holds great promise to promote the development of effective and above all safe vaccines. Hence the future focus should be placed on enhancing their efficacy, mainly through novel approaches in designing structural derivatives, formulations, delivery systems and routes of administration. As safety has been the major issue in development of novel vaccines, this new approach will probably result in new discoveries in designing safe and effective vaccines.

Commercial applications of telemedicine

NASA Technical Reports Server (NTRS)

Natiello, Thomas A.

1991-01-01

Telemedicine Systems Corporation was established in 1976 and is a private commercial supplier of telemedicine systems. These systems are various combinations of communications and diagnostic technology, designed to allow the delivery of health care services to remote facilities. The technology and the health care services are paid for by the remote facilities, such as prisons.

Integrating SAP to Information Systems Curriculum: Design and Delivery

ERIC Educational Resources Information Center

Wang, Ming

2011-01-01

Information Systems (IS) education is being transformed from the segmented applications toward the integrated enterprise-wide system software Enterprise Resource Planning (ERP). ERP is a platform that integrates all business functions with its centralized data repository shared by all the business operations in the enterprise. This tremendous…

Learning Resources for Community Education: Design Notes on Delivery Systems.

ERIC Educational Resources Information Center

Bhola, H. S.

A comprehensive and adaptable system of organizational arrangements is proposed in this document that will enable educational planners in Latin American countries to develop and deliver learning resources for community education and community action programs. A three-tier system of learning resources centers for community education is described.…

Recent Perspectives in Ocular Drug Delivery

PubMed Central

Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

2015-01-01

Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

Towards soft robotic devices for site-specific drug delivery.

PubMed

Alici, Gursel

2015-01-01

Considerable research efforts have recently been dedicated to the establishment of various drug delivery systems (DDS) that are mechanical/physical, chemical and biological/molecular DDS. In this paper, we report on the recent advances in site-specific drug delivery (site-specific, controlled, targeted or smart drug delivery are terms used interchangeably in the literature, to mean to transport a drug or a therapeutic agent to a desired location within the body and release it as desired with negligibly small toxicity and side effect compared to classical drug administration means such as peroral, parenteral, transmucosal, topical and inhalation) based on mechanical/physical systems consisting of implantable and robotic drug delivery systems. While we specifically focus on the robotic or autonomous DDS, which can be reprogrammable and provide multiple doses of a drug at a required time and rate, we briefly cover the implanted DDS, which are well-developed relative to the robotic DDS, to highlight the design and performance requirements, and investigate issues associated with the robotic DDS. Critical research issues associated with both DDSs are presented to describe the research challenges ahead of us in order to establish soft robotic devices for clinical and biomedical applications.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats.

PubMed

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats

PubMed Central

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm. PMID:27336852

Clinical review: The hospital of the future - building intelligent environments to facilitate safe and effective acute care delivery

PubMed Central

2012-01-01

The translation of knowledge into rational care is as essential and pressing a task as the development of new diagnostic or therapeutic devices, and is arguably more important. The emerging science of health care delivery has identified the central role of human factor ergonomics in the prevention of medical error, omission, and waste. Novel informatics and systems engineering strategies provide an excellent opportunity to improve the design of acute care delivery. In this article, future hospitals are envisioned as organizations built around smart environments that facilitate consistent delivery of effective, equitable, and error-free care focused on patient-centered rather than provider-centered outcomes. PMID:22546172

Hot conditioning equipment conceptual design report

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

Bradshaw, F.W., Westinghouse Hanford

1996-08-06

This report documents the conceptual design of the Hot Conditioning System Equipment. The Hot conditioning System will consist of two separate designs: the Hot Conditioning System Equipment; and the Hot Conditioning System Annex. The Hot Conditioning System Equipment Design includes the equipment such as ovens, vacuum pumps, inert gas delivery systems, etc.necessary to condition spent nuclear fuel currently in storage in the K Basins of the Hanford Site. The Hot Conditioning System Annex consists of the facility of house the Hot Conditioning System. The Hot Conditioning System will be housed in an annex to the Canister Storage Building. The Hotmore » Conditioning System will consist of pits in the floor which contain ovens in which the spent nuclear will be conditioned prior to interim storage.« less

A review of implantable biosensors for closed-loop glucose control and other drug delivery applications.

PubMed

Scholten, Kee; Meng, Ellis

2018-06-15

Closed-loop drug delivery promises autonomous control of pharmacotherapy through the continuous monitoring of biomarker levels. For decades, researchers have strived for portable closed-loop systems capable of treating ambulatory patients with chronic conditions such as diabetes mellitus. After years of development, the first of these systems have left the laboratory and entered commercial use. This long-awaited advance reflects recent development of chronically stable implantable biosensors able to accurately measure biomarker levels in vivo. This review discusses the role of implantable biosensors in closed-loop drug delivery applications, with the intent to provide a resource for engineers and researchers studying such systems. We provide an overview of common biosensor designs and review the principle challenges in implementing long indwelling sensors: namely device sensitivity, selectivity, and lifetime. This review examines novel advances in transducer design, biological interface, and material biocompatibility, with a focus on recent academic and commercial work which provide successful strategies to overcome perennial challenges. This review focuses primarily on the topics of closed-loop glucose control and continuous glucose monitoring biosensors, which make up the overwhelming majority of published research in this area. We conclude with an overview of recent advances in closed-loop systems targeting applications outside blood glucose management. Copyright © 2018 Elsevier B.V. All rights reserved.

Designing oral vaccines targeting intestinal dendritic cells.

PubMed

Devriendt, Bert; De Geest, Bruno G; Cox, Eric

2011-04-01

Most pathogens colonize and invade the host at mucosal surfaces, such as the lung and the intestine. To combat intestinal pathogens the induction of local adaptive immune responses is required, which is mainly achieved through oral vaccination. However, most vaccines are ineffective when given orally owing to the hostile environment in the gastrointestinal tract. The encapsulation of antigens in biodegradable microparticulate delivery systems enhances their immunogenicity; however, the uptake of these delivery systems by intestinal immune cells is rather poor. Surface decoration of the particulates with targeting ligands could increase the uptake and mediate the selective targeting of the vaccine to intestinal antigen-presenting cells, including dendritic cells. In this review, current knowledge on dendritic cell subsets is discussed, along with progress in the development of selective antigen targeting to these cells, in addition to focusing on data obtained in mice and, where possible, the pig, as a non-rodent animal model for humans. Moreover, the potential use and benefits of Fcγ receptor-mediated targeting of antigen delivery systems are highlighted. In conclusion, dendritic cell targeting ligands grafted on antigen carrier systems should preferably bind to a conserved endocytotic receptor, facilitating the design of a multispecies vaccine platform, which could elicit robust protective immune responses against enteric pathogens.

Intracellular delivery of peptide nucleic acid and organic molecules using zeolite-L nanocrystals.

PubMed

Bertucci, Alessandro; Lülf, Henning; Septiadi, Dedy; Manicardi, Alex; Corradini, Roberto; De Cola, Luisa

2014-11-01

The design and synthesis of smart nanomaterials can provide interesting potential applications for biomedical purposes from bioimaging to drug delivery. Manufacturing multifunctional systems in a way to carry bioactive molecules, like peptide nucleic acids able to recognize specific targets in living cells, represents an achievement towards the development of highly selective tools for both diagnosis and therapeutics. This work describes a very first example of the use of zeolite nanocrystals as multifunctional nanocarriers to deliver simultaneously PNA and organic molecules into living cells. Zeolite-L nanocrystals are functionalized by covalently attaching the PNA probes onto the surface, while the channel system is filled with fluorescent guest molecules. The cellular uptake of the PNA/Zeolite-L hybrid material is then significantly increased by coating the whole system with a thin layer of biodegradable poly-L-lysine. The delivery of DAPI as a model drug molecule, inserted into the zeolite pores, is also demonstrated to occur in the cells, proving the multifunctional ability of the system. Using this zeolite nanosystem carrying PNA probes designed to target specific RNA sequences of interest in living cells could open new possibilities for theranostic and gene therapy applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Columnar transmitter based wireless power delivery system for implantable device in freely moving animals.

PubMed

Eom, Kyungsik; Jeong, Joonsoo; Lee, Tae Hyung; Lee, Sung Eun; Jun, Sang Bum; Kim, Sung June

2013-01-01

A wireless power delivery system is developed to deliver electrical power to the neuroprosthetic devices that are implanted into animals freely moving inside the cage. The wireless powering cage is designed for long-term animal experiments without cumbersome wires for power supply or the replacement of batteries. In the present study, we propose a novel wireless power transmission system using resonator-based inductive links to increase power efficiency and to minimize the efficiency variations. A columnar transmitter coil is proposed to provide lateral uniformity of power efficiency. Using this columnar transmitter coil, only 7.2% efficiency fluctuation occurs from the maximum transmission efficiency of 25.9%. A flexible polymer-based planar type receiver coil is fabricated and assembled with a neural stimulator and an electrode. Using the designed columnar transmitter coil, the implantable device successfully operates while it moves freely inside the cage.

A Meta-heuristic Approach for Variants of VRP in Terms of Generalized Saving Method

NASA Astrophysics Data System (ADS)

Shimizu, Yoshiaki

Global logistic design is becoming a keen interest to provide an essential infrastructure associated with modern societal provision. For examples, we can designate green and/or robust logistics in transportation systems, smart grids in electricity utilization systems, and qualified service in delivery systems, and so on. As a key technology for such deployments, we engaged in practical vehicle routing problem on a basis of the conventional saving method. This paper extends such idea and gives a general framework available for various real-world applications. It can cover not only delivery problems but also two kind of pick-up problems, i.e., straight and drop-by routings. Moreover, multi-depot problem is considered by a hybrid approach with graph algorithm and its solution method is realized in a hierarchical manner. Numerical experiments have been taken place to validate effectiveness of the proposed method.

Design-Build in Public School Construction: A Post Hearing Briefing. A Report of the Joint Legislative Audit Committee.

ERIC Educational Resources Information Center

California State Legislature, Sacramento. Joint Legislative Audit Committee.

The California legislature's Joint Legislative Audit Committee has issued a report on the design-build versus the design-bid-build process and offers a hybrid approach combining the two systems as a way of achieving the greatest cost efficiency at the least risk on public agencies. The cost benefits of faster delivery of the design-build method…

Hollow waveguide for giant Er:YAG laser pulses transfer

NASA Astrophysics Data System (ADS)

Nemec, Michal; Jelinkova, Helena; Koranda, Petr; Cech, Miroslav; Sulc, Jan; Miyagi, Mitsunobu; Shi, Yi-Wei; Matsuura, Yuji

2004-06-01

Short Er:YAG laser pulses were delivered by a cyclic olefin polymer coated silver hollow glass (COP/Ag) waveguide specially designed for a high power radiation. Er:YAG laser was Q-switched by an electro-optic shutter - LiNbO3 Pockels cell with Brewster angle cut input/output faces. The maximum energy output obtained from this system was 29 mJ with the length of pulse 69 ns corresponding to 420 kW output peak power. The system was working with the repetition rate of 1.5 Hz. A delivery system composed of a lens (f = 40 mm), protector and waveguide with the 700/850 μm diameter and 50 cm or 1 m length. The measured maximum delivered intensity was 86 MW/cm2 what corresponds to the transmission of 78.6 % for whole delivery system. Using of a sealed cap, this delivery system gives a possibility of the contact surgical treatment in many medicine branches, for example ophthalmology, urology or dentistry.

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

PubMed

Chen, Zhi; Wang, Ting; Yan, Qing

2018-02-01

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

Orally disintegrating films: A modern expansion in drug delivery system.

PubMed

Irfan, Muhammad; Rabel, Sumeira; Bukhtar, Quratulain; Qadir, Muhammad Imran; Jabeen, Farhat; Khan, Ahmed

2016-09-01

Over the past few decades, tendency toward innovative drug delivery systems has majorly increased attempts to ensure efficacy, safety and patient acceptability. As discovery and development of new chemical agents is a complex, expensive and time consuming process, so recent trends are shifting toward designing and developing innovative drug delivery systems for existing drugs. Out of those, drug delivery system being very eminent among pediatrics and geriatrics is orally disintegrating films (ODFs). These fast disintegrating films have superiority over fast disintegrating tablets as the latter are associated with the risks of choking and friability. This drug delivery system has numerous advantages over conventional fast disintegrating tablets as they can be used for dysphasic and schizophrenic patients and are taken without water due to their ability to disintegrate within a few seconds releasing medication in mouth. Various approaches are employed for formulating ODFs and among which solvent casting and spraying methods are frequently used. Generally, hydrophilic polymers along with other excipients are used for preparing ODFs which allow films to disintegrate quickly releasing incorporated active pharmaceutical ingredient (API) within seconds. Orally disintegrating films have potential for business and market exploitation because of their myriad of benefits over orally disintegrating tablets. This present review attempts to focus on benefits, composition, approaches for formulation and evaluation of ODFs. Additionally, the market prospect of this innovative dosage form is also targeted.

KENNEDY SPACE CENTER, FLA. - The apparatus shown was designed to hold microcapsules for research on mission STS-107. It is one over several included in the Commercial ITA Biomedical Experiments payload. The box was recently recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions.

NASA Image and Video Library

2003-05-06

KENNEDY SPACE CENTER, FLA. - The apparatus shown was designed to hold microcapsules for research on mission STS-107. It is one over several included in the Commercial ITA Biomedical Experiments payload. The box was recently recovered during the search for Columbia debris. The drug delivery system and spaceflight hardware was developed jointly by JSC, the Institute for Research Inc. and Instrumentation Technology Associates Inc. to conduct microencapsulation experiments under microgravity conditions.

Design of Drug Delivery Methods for the Brain and Central Nervous System

NASA Astrophysics Data System (ADS)

Lueshen, Eric

Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection-enhanced drug delivery (CED) is a technique used to bypass the BBB via direct intracranial injection using a catheter driven by a positive pressure gradient from an infusion pump. Although CED boasts the advantage of achieving larger drug distribution volumes compared to diffusion driven methods, difficulty in predicting drug spread and preventing backflow along the catheter shaft commonly occur. In this dissertation, a method for predicting drug distributions in the brain using diffusion tensor imaging (DTI) data is employed to show how small variations in catheter placement can lead to drastically different volumes of drug distribution in vivo. The impact that microfluid flow has on deformable brain phantom gel is studied in order to elucidate the causes of backflow, and the results are used to develop backflow-free catheters with safe volumetric flow rates up to 10 ?l/min. Through implementation of our backflow-free catheter designs, physicians will be able to target specific regions of the brain with improved accuracy, increased drug concentration, and larger drug distribution geometries. Intrathecal (IT) drug delivery involves direct drug infusion into the spinal canal and has become standard practice for treating many CNS diseases. Although IT drug delivery boasts the advantage of reduced systemic toxicity compared to oral and intravenous techniques, current IT delivery protocols lack a means of sufficient drug targeting at specific locations of interest within the CNS. In this dissertation, the method of intrathecal magnetic drug targeting (IT-MDT) is developed to overcome the limited targeting capabilities of standard IT drug delivery protocols. The basic idea behind IT-MDT is to guide intrathecally-injected, drug-functionalized magnetic nanoparticles (MNPs) using an external magnetic field to diseased regions within the spinal canal. Cerebrospinal fluid (CSF) transport phenomena are studied, and in vitro human spine surrogates are built. Experiments are run on the in vitro human spine model to determine the feasibility of IT-MDT and to develop novel treatment therapies. Computer simulations are performed to optimize magnetic field placement and/or implant design for generating high gradient magnetic fields, as well as to study how these fields aid in therapeutic nanoparticle localization. Large collection efficiencies of MNPs were achieved during in vitro IT-MDT and implant-assisted IT-MDT experiments with concentration levels nearly nine times that of the control when no magnetic field was present. Testing different magnetizable implants showed that implant design is a key factor in achieving the largest MNP collection efficiency within the targeting region. Knowledge gained from the in vitro IT-MDT experiments and simulations will be used in the future to develop IT-MDT methods in animals and humans.

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

DOT National Transportation Integrated Search

2009-11-01

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

Rethinking modeling framework design: object modeling system 3.0

USDA-ARS?s Scientific Manuscript database

The Object Modeling System (OMS) is a framework for environmental model development, data provisioning, testing, validation, and deployment. It provides a bridge for transferring technology from the research organization to the program delivery agency. The framework provides a consistent and efficie...

Preliminary analysis of hub and spoke air freight distribution system

NASA Technical Reports Server (NTRS)

Whitehead, A. H., Jr.

1978-01-01

A brief analysis is made of the hub and spoke air freight distribution system which would employ less than 15 hub centers world wide with very large advanced distributed-load freighters providing the line-haul delivery between hubs. This system is compared to a more conventional network using conventionally-designed long-haul freighters which travel between numerous major airports. The analysis calculates all of the transportation costs, including handling charges and pickup and delivery costs. The results show that the economics of the hub/spoke system are severely compromised by the extensive use of feeder aircraft to deliver cargo into and from the large freighter terminals. Not only are the higher costs for the smaller feeder airplanes disadvantageous, but their use implies an additional exchange of cargo between modes compared to truck delivery. The conventional system uses far fewer feeder airplanes, and in many cases, none at all. When feeder aircraft are eliminated from the hub/spoke system, however, that system is universally more economical than any conventional system employing smaller line-haul aircraft.

Extent of Integration of Priority Interventions into General Health Systems: A Case Study of Neglected Tropical Diseases Programme in the Western Region of Ghana.

PubMed

Mensah, Ernest O; Aikins, Moses K; Gyapong, Margaret; Anto, Francis; Bockarie, Moses J; Gyapong, John O

2016-05-01

The global health system has a large arsenal of interventions, medical products and technologies to address current global health challenges. However, identifying the most effective and efficient strategies to deliver these resources to where they are most needed has been a challenge. Targeted and integrated interventions have been the main delivery strategies. However, the health system discourse increasingly favours integrated strategies in the context of functionally merging targeted interventions with multifunctional health care delivery systems with a focus on strengthening country health systems to deliver needed interventions. Neglected Tropical Diseases (NTD) have been identified to promote and perpetuate poverty hence there has been global effort to combat these diseases. The Neglected Tropical Diseases Programme (NTDP) in Ghana has a national programme team and office, however, it depends on the multifunctional health delivery system at the regional and district level to implement interventions. The NTDP seeks further health system integration to accelerate achievement of coverage targets. The study estimated the extent of integration of the NTDP at the national, regional and district levels to provide evidence to guide further integration. The research design was a descriptive case study that interviewed key persons involved in the programme at the three levels of the health system as well as extensive document review. Integration was assessed on two planes-across health system functions-stewardship and governance, financing, planning, service delivery, monitoring and evaluation and demand generation; and across three administrative levels of the health system-national, regional and district. A composite measure of integration designated Cumulative Integration Index (CII) with a range of 0.00-1.00 was used to estimate extent of integration at the three levels of the health system. Service delivery was most integrated while financing and planning were least integrated. Extent of integration was partial at all levels of the health system with a CII of 0.48-0.68; however it was higher at the district compared to the national and regional levels. To ensure further integration of the NTDP, planning and finance management activities must be decentralized to involve regional and district levels of the health system. The study provides an empirical measure of extent of integration and indicators to guide further integration.

Utilizing food effects to overcome challenges in delivery of lipophilic bioactives: structural design of medical and functional foods.

PubMed

McClements, David Julian

2013-12-01

The oral bioavailability of many lipophilic bioactives, such as pharmaceuticals and nutraceuticals, is relatively low due to their poor solubility, permeability and/or chemical stability within the human gastrointestinal tract (GIT). The oral bioavailability of lipophilic bioactives can be improved by designing food matrices that control their release, solubilization, transport and absorption within the GIT. This article discusses the challenges associated with delivering lipophilic bioactive components, the impact of food composition and structure on oral bioavailability and the design of functional and medical foods for improving the oral bioavailability of lipophilic bioactives. Food-based delivery systems can be used to improve the oral bioavailability of lipophilic bioactives. There are a number of potential advantages to delivering lipophilic bioactives using functional or medical foods: greater compliance than conventional delivery forms; increased bioavailability and efficacy; and reduced variability in biological effects. However, food matrices are structurally complex multicomponent materials and research is still needed to identify optimum structures and compositions for particular bioactives.

Consistency and Reproducibility of Bioaerosol Delivery for Infectivity Studies on Mice

DTIC Science & Technology

2010-03-01

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

Changes in Local Public Health System Performance Before and After Attainment of National Accreditation Standards.

PubMed

Ingram, Richard C; Mays, Glen P; Kussainov, Nurlan

The aim of this study is to investigate the impact of Public Health Accreditation Board (PHAB) accreditation on the delivery of public health services and on participation from other sectors in the delivery of public health services in local public health systems. This study uses a longitudinal repeated measures design to identify differences between a cohort of public health systems containing PHAB-accredited local health departments and a cohort of public health systems containing unaccredited local health departments. It uses data spanning from 2006 to 2016. This study examines a cohort of local public health systems that serves large populations and contains unaccredited and PHAB-accredited local health departments. Data in this study were collected from the directors of health departments that include local public health systems followed in the National Longitudinal Study of Public Health Systems. The intervention examined is PHAB accreditation. The study focuses on 4 areas: the delivery of core public health services, local health department contribution toward these services, participation in the delivery of these services by other members of the public health system, and public health system makeup. Prior to the advent of accreditation, public health systems containing local health departments that were later accredited by PHAB appear quite similar to their unaccredited peers. Substantial differences between the 2 cohorts appear to manifest themselves after the advent of accreditation. Specifically, the accredited cohort seems to offer a broader array of public health services, involve more partners in the delivery of those services, and enjoy a higher percentage of comprehensive public health systems. The results of this study suggest that accreditation may yield significant benefits and may help public health systems develop the public health system capital necessary to protect and promote the public's health.

Hybrid dendrimer hydrogel/poly(lactic-co-glycolic acid) nanoparticle platform: an advanced vehicle for topical delivery of antiglaucoma drugs and a likely solution to improving compliance and adherence in glaucoma management.

PubMed

Yang, Hu; Leffler, Christopher T

2013-03-01

Glaucoma therapy typically begins with topical medications, of which there are 4 major classes in common use in the United States: beta-adrenergic antagonists, alpha-agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Unfortunately, all 4 classes require at least daily dosing, and 3 of the 4 classes are approved to be administered 2 or 3 times daily. This need for frequent dosing with multiple medications makes compliance difficult. Longer-acting formulations and combinations that require less frequent administration might improve compliance and therefore medication effectiveness. Recently, we developed an ocular drug delivery system, a hybrid dendrimer hydrogel/poly(lactic-co-glycolic acid) nanoparticle platform for delivering glaucoma therapeutics topically. This platform is designed to deliver glaucoma drugs to the eye efficiently and release the drug in a slow fashion. Furthermore, this delivery platform is designed to be compatible with many of the glaucoma drugs that are currently approved for use. In this article, we review this new delivery system with in-depth discussion of its structural features, properties, and preclinical application in glaucoma treatment. In addition, future directions and translational efforts for marketing this technology are elaborated.

Transdermal delivery of biomacromolecules using lipid-like nanoparticles

NASA Astrophysics Data System (ADS)

Bello, Evelyn A.

The transdermal delivery of biomacromolecules, including proteins and nucleic acids, is challenging, owing to their large size and the penetration-resistant nature of the stratum corneum. Thus, an urgent need exists for the development of transdermal delivery methodologies. This research focuses on the use of cationic lipid-like nanoparticles (lipidoids) for the transdermal delivery of proteins, and establishes an in vitro model for the study. The lipidoids used were first combinatorially designed and synthesized; afterwards, they were employed for protein encapsulation in a vesicular system. A skin penetration study demonstrated that lipidoids enhance penetration depth in a pig skin model, overcoming the barrier that the stratum corneum presents. This research has successfully identified active lipidoids capable of efficiently penetrating the skin; therefore, loading proteins into lipidoid nanoparticles will facilitate the transdermal delivery of proteins. Membrane diffusion experiments were used to confirm the results. This research has confirmed that lipidoids are a suitable material for transdermal protein delivery enhancement.

Solar heating and cooling system design and development

NASA Technical Reports Server (NTRS)

1978-01-01

The progress of the program during the sixth program quarter is reported. The program calls for the development and delivery of eight prototype solar heating and cooling systems for installation and operational test. The William O'Brien single-family heating system was installed and is operational. The New Castle single-family heating residence is under construction. The Kansas University (KU) system is in the final design stages. The 25 ton cooling subsystem for KU is the debugging stage. Pressure drops that were greater than anticipated were encountered. The 3 ton simulation work is being finalized and the design parameters for the Rankine system were determined from simulation output.

Individualization for Education at Scale: MIIC Design and Preliminary Evaluation

ERIC Educational Resources Information Center

Brinton, Christopher G.; Rill, Ruediger; Ha, Sangtae; Chiang, Mung; Smith, Robert; Ju, William

2015-01-01

We present the design, implementation, and preliminary evaluation of our Adaptive Educational System (AES): the Mobile Integrated and Individualized Course (MIIC). MIIC is a platform for personalized course delivery which integrates lecture videos, text, assessments, and social learning into a mobile native app, and collects clickstream-level…

Adsorption of doxorubicin on citrate-capped gold nanoparticles: insights into engineering potent chemotherapeutic delivery systems

NASA Astrophysics Data System (ADS)

Curry, Dennis; Cameron, Amanda; MacDonald, Bruce; Nganou, Collins; Scheller, Hope; Marsh, James; Beale, Stefanie; Lu, Mingsheng; Shan, Zhi; Kaliaperumal, Rajendran; Xu, Heping; Servos, Mark; Bennett, Craig; Macquarrie, Stephanie; Oakes, Ken D.; Mkandawire, Martin; Zhang, Xu

2015-11-01

Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates. Electronic supplementary information (ESI) available: DOX-AuNP absorption spectra and colored solution images, citrate displacement data, original DOX-AuNP loading isotherm, XPS data and TEM micrographs, modelling data. See DOI: 10.1039/c5nr05826k

On-Demand Drug Delivery System Using Micro-organogels with Gold Nanorods

PubMed Central

2016-01-01

In this study, we designed a biocompatible drug carrier: micro-organogels prepared by emulsification using vegetable oils and self-assembled gelator fibers. Flurbiprofen was chosen as a hydrophobic model drug and is classified as a nonsteroidal anti-inflammatory drug. In the absence of NIR light, flurbiprofen encapsulated in micro-organogels with gold nanorods (GNRs) was released slowly, while release was accelerated in the presence of NIR light due to the increase in the temperature surrounding the GNRs that transforms the gels into liquid. These results suggest that our system can be efficiently used as a versatile scaffold for on-demand drug delivery systems. PMID:27994743

Semiconductor laser insert with uniform illumination for use in photodynamic therapy

NASA Astrophysics Data System (ADS)

Charamisinau, Ivan; Happawana, Gemunu; Evans, Gary; Rosen, Arye; Hsi, Richard A.; Bour, David

2005-08-01

A low-cost semiconductor red laser light delivery system for esophagus cancer treatment is presented. The system is small enough for insertion into the patient's body. Scattering elements with nanoscale particles are used to achieve uniform illumination. The scattering element optimization calculations, with Mie theory, provide scattering and absorption efficiency factors for scattering particles composed of various materials. The possibility of using randomly deformed spheres and composite particles instead of perfect spheres is analyzed using an extension to Mie theory. The measured radiation pattern from a prototype light delivery system fabricated using these design criteria shows reasonable agreement with the theoretically predicted pattern.

WaterSense Labeled New Homes

EPA Pesticide Factsheets

Homes built to meet EPA's specification can earn the WaterSense label. EPA criteria include WaterSense labeled plumbing fixtures, efficient hot water delivery systems, water-smart landscape design, and other features.

Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery.

PubMed

Qi, Dingqing; Gong, Feirong; Teng, Xin; Ma, Mingming; Wen, Huijing; Yuan, Weihao; Cheng, Yi; Lu, Chong

2017-10-01

Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB) 2 ) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB) 2 was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (~17-19 nm) and narrow size distribution (PI < 0.1), which can be lyophilized and easily reconstituted in saline without significant change in particle size distribution. In vitro drug-release study demonstrated that mPEG-PLA-Lys(FB) 2 micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB) 2 micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.

Extent of Integration of Priority Interventions into General Health Systems: A Case Study of Neglected Tropical Diseases Programme in the Western Region of Ghana

PubMed Central

Mensah, Ernest O.; Aikins, Moses K.; Gyapong, Margaret; Anto, Francis; Bockarie, Moses J.; Gyapong, John O.

2016-01-01

Background The global health system has a large arsenal of interventions, medical products and technologies to address current global health challenges. However, identifying the most effective and efficient strategies to deliver these resources to where they are most needed has been a challenge. Targeted and integrated interventions have been the main delivery strategies. However, the health system discourse increasingly favours integrated strategies in the context of functionally merging targeted interventions with multifunctional health care delivery systems with a focus on strengthening country health systems to deliver needed interventions. Neglected Tropical Diseases (NTD) have been identified to promote and perpetuate poverty hence there has been global effort to combat these diseases. The Neglected Tropical Diseases Programme (NTDP) in Ghana has a national programme team and office, however, it depends on the multifunctional health delivery system at the regional and district level to implement interventions. The NTDP seeks further health system integration to accelerate achievement of coverage targets. The study estimated the extent of integration of the NTDP at the national, regional and district levels to provide evidence to guide further integration. Methodology/Principal Findings The research design was a descriptive case study that interviewed key persons involved in the programme at the three levels of the health system as well as extensive document review. Integration was assessed on two planes—across health system functions–stewardship and governance, financing, planning, service delivery, monitoring and evaluation and demand generation; and across three administrative levels of the health system–national, regional and district. A composite measure of integration designated Cumulative Integration Index (CII) with a range of 0.00–1.00 was used to estimate extent of integration at the three levels of the health system. Service delivery was most integrated while financing and planning were least integrated. Extent of integration was partial at all levels of the health system with a CII of 0.48–0.68; however it was higher at the district compared to the national and regional levels. Conclusions/Significance To ensure further integration of the NTDP, planning and finance management activities must be decentralized to involve regional and district levels of the health system. The study provides an empirical measure of extent of integration and indicators to guide further integration. PMID:27203854

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.

Non-viral gene therapy for bone tissue engineering.

PubMed

Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

2013-01-01

The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

Oral delivery of peptides and proteins using lipid-based drug delivery systems.

PubMed

Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

2012-10-01

In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism by which intestinal absorption of peptides and proteins is promoted. The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides and proteins. Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve the design and development of lipid-based DDS with the desired bioavailability and therapeutic profile.

Mucus interactions with liposomes encapsulating bioactives: Interfacial tensiometry and cellular uptake on Caco-2 and cocultures of Caco-2/HT29-MTX.

PubMed

Li, Yang; Arranz, Elena; Guri, Anilda; Corredig, Milena

2017-02-01

Structuring of delivery matrices in foods aquires careful designing for optimal delivery and subsiquent absorption of the beneficial compounds in the gut. There has been quite improvement in mimicking digestion and absorption in vitro but as of yet little is understood on mucus interference in nutrient absorption Therefore in this study interactions of human intestinal mucus with milk and soy phospholipids liposomes carring hydrophilic (epigallocatechin-3-gallate) or hydrophobic (β-carotene) bioactive molecules were investigated. Liposomes of about 100nm were obtained using microfluidization and their behaviour with the human intestinal mucus were evaluated using drop shape tensiometry. The chemistry of the liposomes (milk or soy) and the encapsulated bioactive structure can affect the viscoelastic behaviour of the complex itself. Empty or loaded liposomes were differently interacting with the mucus at the interface. Mucus-liposomes interactions were also studied using cell cultures, Caco-2 (without mucus) and cocultures Caco-2/HT29-MTX (mucus producing). The interaction of mucus layer with liposomes was at some extent aligned with rheological studies. This work demonstrated that delivery systems may interact with the mucosal surface of intestinal cells, and in vitro approaches allow for screening of such interactions. These highlights could help us in carefully designing the delivery systems and moreover choosing the right carrier and/or bioactive that does not jeopardize the optimal delivery of the bioactive structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Self assembled materials: design strategies and drug delivery perspectives.

PubMed

Verma, Gunjan; Hassan, P A

2013-10-28

Self assembly of small molecules in complex supramolecular structures provides a new avenue in the development of materials for drug delivery applications. Owing to the low aqueous solubility of various drugs, an effective delivery system is often required to reach sufficient drug bioavailability and/or to facilitate clinical use. Micelles, amphiphilic gels, vesicles (liposomes), nanodisks, cubosomes, colloidosomes, tubules, microemulsions, lipid particles, polyelectrolyte capsules etc. are some of the intriguing structures formed via self assembly. As well as enabling improved solubilization, such materials can be tuned to offer a range of other advantages, including controlled or stimuli sensitive drug release, protection from drug hydrolysis and chemical or enzymatic degradation, a reduction in toxicity, improvement of drug availability, prevention of RES uptake or selective targeting to organelles etc. Such multiple functionalities can be brought together by self assembly of different functional molecules. This route offers a cost effective means of developing drug delivery carriers tailored to specific needs. Our current understanding of the microstructure evolution of self assembled materials will go a long way towards designing/selecting molecules to create well defined structures. We believe that most of the potential resources mentioned above are untapped and that there is a need to further strengthen research in this area to fully exploit their potential. Selective cross linking of core or shell, stimuli sensitive amphiphiles, prodrug amphiphiles, antibody coupled amphiphiles etc. are only some of the new approaches for the development of effective drug delivery systems via self assembly.

Treatment of otitis media by transtympanic delivery of antibiotics

PubMed Central

Yang, Rong; Sabharwal, Vishakha; Okonkwo, Obiajulu S.; Shlykova, Nadya; Tong, Rong; Lin, Lily Yun; Wang, Weiping; Guo, Shutao; Rosowski, John J.; Pelton, Stephen I.; Kohane, Daniel S.

2017-01-01

Otitis media is the most common reason U.S. children receive antibiotics. The requisite 7- to 10-day course of oral antibiotics can be challenging to deliver in children, entails potential systemic toxicity, and encourages selection of antimicrobial-resistant bacteria. We developed a drug delivery system that, when applied once to the tympanic membrane through the external auditory canal, delivers an entire course of antimicrobial therapy to the middle ear. A penta-block copolymer poloxamer 407–polybutylphosphoester (P407-PBP) was designed to flow easily during application and then to form a mechanically strong hydrogel on the tympanic membrane. U.S. Food and Drug Administration–approved chemical permeation enhancers within the hydrogel assisted flux of the antibiotic ciprofloxacin across the membrane. This drug delivery system completely eradicated otitis media from nontypable Haemophilus influenzae (NTHi) in 10 of 10 chinchillas, whereas only 62.5% of animals receiving 1% ciprofloxacin alone had cleared the infection by day 7. The hydrogel system was biocompatible in the ear, and ciprofloxacin was undetectable systemically (in blood), confirming local drug delivery and activity. This fast-gelling hydrogel could improve compliance, minimize side effects, and prevent systemic distribution of antibiotics in one of the most common pediatric illnesses, possibly minimizing the development of antibiotic resistance. PMID:27629487

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.

PubMed

Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

2010-01-01

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

Machine-Assisted Reference Section 1980 Program: Proceedings.

ERIC Educational Resources Information Center

Nitecki, Danuta A.

1980-01-01

The three papers presented discuss the components of the pricing structure for online service vendors (Roger Summit); describe an information system designed to provide agricultural weather data to farmers (Lehnert and Scott); and explore the impact of information delivery systems for the home (Mark Plakias). (FM)

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Rate-programming of nano-particulate delivery systems for smart bioactive scaffolds in tissue engineering.

PubMed

Izadifar, Mohammad; Haddadi, Azita; Chen, Xiongbiao; Kelly, Michael E

2015-01-09

Development of smart bioactive scaffolds is of importance in tissue engineering, where cell proliferation, differentiation and migration within scaffolds can be regulated by the interactions between cells and scaffold through the use of growth factors (GFs) and extra cellular matrix peptides. One challenge in this area is to spatiotemporally control the dose, sequence and profile of release of GFs so as to regulate cellular fates during tissue regeneration. This challenge would be addressed by rate-programming of nano-particulate delivery systems, where the release of GFs via polymeric nanoparticles is controlled by means of the methods of, such as externally-controlled and physicochemically/architecturally-modulated so as to mimic the profile of physiological GFs. Identifying and understanding such factors as the desired release profiles, mechanisms of release, physicochemical characteristics of polymeric nanoparticles, and externally-triggering stimuli are essential for designing and optimizing such delivery systems. This review surveys the recent studies on the desired release profiles of GFs in various tissue engineering applications, elucidates the major release mechanisms and critical factors affecting release profiles, and overviews the role played by the mathematical models for optimizing nano-particulate delivery systems. Potentials of stimuli responsive nanoparticles for spatiotemporal control of GF release are also presented, along with the recent advances in strategies for spatiotemporal control of GF delivery within tissue engineered scaffolds. The recommendation for the future studies to overcome challenges for developing sophisticated particulate delivery systems in tissue engineering is discussed prior to the presentation of conclusions drawn from this paper.

Electromagnet Weight Reduction in a Magnetic Levitation System for Contactless Delivery Applications

PubMed Central

Hong, Do-Kwan; Woo, Byung-Chul; Koo, Dae-Hyun; Lee, Ki-Chang

2010-01-01

This paper presents an optimum design of a lightweight vehicle levitation electromagnet, which also provides a passive guide force in a magnetic levitation system for contactless delivery applications. The split alignment of C-shaped electromagnets about C-shaped rails has a bad effect on the lateral deviation force, therefore, no-split positioning of electromagnets is better for lateral performance. This is verified by simulations and experiments. This paper presents a statistically optimized design with a high number of the design variables to reduce the weight of the electromagnet under the constraint of normal force using response surface methodology (RSM) and the kriging interpolation method. 2D and 3D magnetostatic analysis of the electromagnet are performed using ANSYS. The most effective design variables are extracted by a Pareto chart. The most desirable set is determined and the influence of each design variable on the objective function can be obtained. The generalized reduced gradient (GRG) algorithm is adopted in the kriging model. This paper’s procedure is validated by a comparison between experimental and calculation results, which shows that the predicted performance of the electromagnet designed by RSM is in good agreement with the simulation results. PMID:22163572

A Low Cost, Self Acting, Liquid Hydrogen Boil-Off Recovery System

NASA Technical Reports Server (NTRS)

Pelfrey, Joy W.; Sharp, Kirk V. (Technical Monitor)

2001-01-01

The purpose of this research was to develop a prototype liquid hydrogen boll-off recovery system. Perform analyses to finalize recovery system cycle, design detail components, fabricate hardware, and conduct sub-component, component, and system level tests leading to the delivery of a prototype system. The design point and off-design analyses identified cycle improvements to increase the robustness of the system by adding a by-pass heat exchanger. Based on the design, analysis, and testing conducted, the recovery system will liquefy 31% of the gaseous boil off from a liquid hydrogen storage tank. All components, including a high speed, miniature turbocompressor, were designed and manufacturing drawings were created. All hardware was fabricated and tests were conducted in air, helium, and hydrogen. Testing validated the design, except for the turbocompressor. A rotor-to-stator clearance issue was discovered as a result of a concentricity tolerance stack-up.

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…

31 CFR 561.324 - Designated Iranian financial institution.

Code of Federal Regulations, 2012 CFR

2012-07-01

... this chapter in connection with Iran's proliferation of weapons of mass destruction or delivery systems for weapons of mass destruction or Iran's support for international terrorism has, since the enactment...

Nanostructured Platforms for the Sustained and Local Delivery of Antibiotics in the Treatment of Osteomyelitis

PubMed Central

Uskoković, Vuk

2015-01-01

This article provides a critical view of the current state of the development of nanoparticulate and other solid-state carriers for the local delivery of antibiotics in the treatment of osteomyelitis. Mentioned are the downsides of traditional means for treating bone infection, which involve systemic administration of antibiotics and surgical debridement, along with the rather imperfect local delivery options currently available in the clinic. Envisaged are more sophisticated carriers for the local and sustained delivery of antimicrobials, including bioresorbable polymeric, collagenous, liquid crystalline, and bioglass- and nanotube-based carriers, as well as those composed of calcium phosphate, the mineral component of bone and teeth. A special emphasis is placed on composite multifunctional antibiotic carriers of a nanoparticulate nature and on their ability to induce osteogenesis of hard tissues demineralized due to disease. An ideal carrier of this type would prevent the long-term, repetitive, and systemic administration of antibiotics and either minimize or completely eliminate the need for surgical debridement of necrotic tissue. Potential problems faced by even hypothetically “perfect” antibiotic delivery vehicles are mentioned too, including (i) intracellular bacterial colonies involved in recurrent, chronic osteomyelitis; (ii) the need for mechanical and release properties to be adjusted to the area of surgical placement; (iii) different environments in which in vitro and in vivo testings are carried out; (iv) unpredictable synergies between drug delivery system components; and (v) experimental sensitivity issues entailing the increasing subtlety of the design of nanoplatforms for the controlled delivery of therapeutics. PMID:25746204

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

NASA Technical Reports Server (NTRS)

1973-01-01

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

Preliminary design package for prototype solar heating and cooling systems

NASA Technical Reports Server (NTRS)

1978-01-01

A summary is given of the preliminary analysis and design activity on solar heating and cooling systems. The analysis was made without site specific data other than weather; therefore, the results indicate performance expected under these special conditions. Major items include a market analysis, design approaches, trade studies and other special data required to evaluate the preliminary analysis and design. The program calls for the development and delivery of eight prototype solar heating and cooling systems for installation and operational test. Two heating and six heating and cooling units will be delivered for Single Family Residences, Multiple-family Residences and commercial applications.

Design, fabrication, testing, and delivery of a solar energy collector system for residential heating and cooling

NASA Technical Reports Server (NTRS)

Holland, T. H.; Borzoni, J. T.

1976-01-01

A low cost flat plate solar energy collector was designed for the heating and cooling of residential buildings. The system meets specified performance requirements, at the desired system operating levels, for a useful life of 15 to 20 years, at minimum cost and uses state-of-the-art materials and technology. The rationale for the design method was based on identifying possible material candidates for various collector components and then selecting the components which best meet the solar collector design requirements. The criteria used to eliminate certain materials were: performance and durability test results, cost analysis, and prior solar collector fabrication experience.

Designing a theory-informed, contextually appropriate intervention strategy to improve delivery of paediatric services in Kenyan hospitals.

PubMed

English, Mike

2013-03-28

District hospital services in Kenya and many low-income countries should deliver proven, effective interventions that could substantially reduce child and newborn mortality. However such services are often of poor quality. Researchers have therefore been challenged to identify intervention strategies that go beyond addressing knowledge, skill, or resource inadequacies to support health systems to deliver better services at scale. An effort to develop a system-oriented intervention tailored to local needs and context and drawing on theory is described. An intervention was designed to improve district hospital services for children based on four main strategies: a reflective process to distill root causes for the observed problems with service delivery; developing a set of possible intervention approaches to address these problems; a search of literature for theory that provided the most appropriate basis for intervention design; and repeatedly moving backwards and forwards between identified causes, proposed interventions, identified theory, and knowledge of the existing context to develop an overarching intervention that seemed feasible and likely to be acceptable and potentially sustainable. In addition to human and resource constraints key problems included failures of relevant professionals to take responsibility for or ownership of the challenge of pediatric service delivery; inadequately prepared, poorly supported leaders of service units (mid-level managers) who are often professionally and geographically isolated and an almost complete lack of useful information for routinely monitoring or understanding service delivery practice or outcomes. A system-oriented intervention recognizing the pivotal role of leaders of service units but addressing the outer and inner setting of hospitals was designed to help shape and support an appropriate role for these professionals. It aims to foster a sense of ownership while providing the necessary understanding, knowledge, and skills for mid-level managers to work effectively with senior managers and frontline staff to improve services. The intervention will include development of an information system, feedback mechanisms, and discussion fora that promote positive change. The vehicle for such an intervention is a collaborative network partnering government and national professional associations. This case is presented to promote discussion on approaches to developing context appropriate interventions particularly in international health.

Image guided drug release from pH-sensitive Ion channel-functionalized stealth liposomes into an in vivo glioblastoma model.

PubMed

Pacheco-Torres, Jesus; Mukherjee, Nobina; Walko, Martin; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdan, Sebastian; Kocer, Armagan

2015-08-01

Liposomal drug delivery vehicles are promising nanomedicine tools for bringing cytotoxic drugs to cancerous tissues selectively. However, the triggered cargo release from liposomes in response to a target-specific stimulus has remained elusive. We report on functionalizing stealth-liposomes with an engineered ion channel and using these liposomes in vivo for releasing an imaging agent into a cerebral glioma rodent model. If the ambient pH drops below a threshold value, the channel generates temporary pores on the liposomes, thus allowing leakage of the intraluminal medicines. By using magnetic resonance spectroscopy and imaging, we show that engineered liposomes can detect the mildly acidic pH of the tumor microenvironment with 0.2 pH unit precision and they release their content into C6 glioma tumors selectively, in vivo. A drug delivery system with this level of sensitivity and selectivity to environmental stimuli may well serve as an optimal tool for environmentally-triggered and image-guided drug release. Cancer remains a leading cause of mortality worldwide. With advances in science, delivery systems of anti-cancer drugs have also become sophisticated. In this article, the authors designed and characterized functionalized liposomal vehicles, which would release the drug payload in a highly sensitive manner in response to a change in pH environment in an animal glioma model. The novel data would enable better future designs of drug delivery systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel drug delivery systems in pain therapy.

PubMed

Al Malyan, M; Becchi, C; Boncinelli, S; Ashammakhi, N

2007-03-01

Pain is an unpleasant sensory experience resulting from damage to bodily tissues. It is considered a significant public health problem because it affects 1/5 of the world population and causes loss of great amounts of money. Pain reflects a mixture of pathological, psychological and genetic conditions that need deep understanding to be efficiently treated. If under-treated, pain results in serious immune and metabolic problems. Pain management faces many problems that limit its control. For instance, efficiency of pain killers is limited, pain killers give rise to serious side effects and inability of drug administration methods to help in pain control. Technology can overcome some of these problems and the introduction of implantable controlled drug delivery systems (CDDS), manufactured from biodegradable materials, offers a solution. Implantable CDDS provide good level of pain control, as they continuously provide drug, reduce side effects and improve patients' compliance. Biodegradable type of implantable CDDS are polymer based devices that are fabricated to locally deliver drugs in a pre-designed manner. They are currently a focus of research in the field of pain therapy in order to explore their chance to offer an alternative to the conventional methods for drug delivery. This paper aims to highlight the dimensions of pain issue and to overview the basics of drug release from polymers used for CDDS in pain management. In addition, it discusses the recent advances in the technologically designed drug delivery systems in the field of pain medicine and their clinical applications. Future perspectives are also presented.

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

PubMed

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

2018-01-01

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

Quality assurance for online adapted treatment plans: benchmarking and delivery monitoring simulation.

PubMed

Li, Taoran; Wu, Qiuwen; Yang, Yun; Rodrigues, Anna; Yin, Fang-Fang; Jackie Wu, Q

2015-01-01

An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system was designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system's performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system's ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.

Biomedical Properties Study of Modified Chitosan Nanoparticles for Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Saboktakin, Mohammad Reza

2013-09-01

The purpose of this review is to discuss and summarize some of the interesting findings and applications of modified chitosan (MCS) and their derivatives in different areas of drug delivery. This review highlights the important applications of MCS in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their uses as recipients in drug formulation are also discussed. This review also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting MCS in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized.

Sulfated Seaweed Polysaccharides as Multifunctional Materials in Drug Delivery Applications

PubMed Central

Cunha, Ludmylla; Grenha, Ana

2016-01-01

In the last decades, the discovery of metabolites from marine resources showing biological activity has increased significantly. Among marine resources, seaweed is a valuable source of structurally diverse bioactive compounds. The cell walls of marine algae are rich in sulfated polysaccharides, including carrageenan in red algae, ulvan in green algae and fucoidan in brown algae. Sulfated polysaccharides have been increasingly studied over the years in the pharmaceutical field, given their potential usefulness in applications such as the design of drug delivery systems. The purpose of this review is to discuss potential applications of these polymers in drug delivery systems, with a focus on carrageenan, ulvan and fucoidan. General information regarding structure, extraction process and physicochemical properties is presented, along with a brief reference to reported biological activities. For each material, specific applications under the scope of drug delivery are described, addressing in privileged manner particulate carriers, as well as hydrogels and beads. A final section approaches the application of sulfated polysaccharides in targeted drug delivery, focusing with particular interest the capacity for macrophage targeting. PMID:26927134

A novel misoprostol delivery system for induction of labor: clinical utility and patient considerations.

PubMed

Stephenson, Megan L; Wing, Deborah A

2015-01-01

Induction of labor is one of the most commonly performed obstetric procedures and will likely become more common as the reproductive population in developed nations changes. As the proportion of women undergoing induction grows, there is a constant search for more efficacious ways to induce labor while maintaining fetal and maternal safety as well as patient satisfaction. With almost half of induced labors requiring cervical ripening, methods for achieving active labor and vaginal delivery are constantly being investigated. Prostaglandins have been shown to be effective induction agents, and specifically vaginal misoprostol, used off-label, have been widely utilized to initiate cervical ripening and active labor. The challenge is to administer this medication accurately while maintaining the ability to discontinue the medication when needed. The misoprostol vaginal insert initiates cervical ripening utilizing a delivery system that controls medication release and can be rapidly removed. This paper reviews the design, development, and clinical utility of the misoprostol vaginal insert for induction of labor as well as patient considerations related to the delivery system.

MicroRNAs as therapeutics for future drug delivery systems in treatment of lung diseases.

PubMed

Dua, Kamal; Hansbro, Nicole G; Foster, Paul S; Hansbro, Philip M

2017-02-01

The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system. In this review, we have summarised the concept of miRNAs and different approaches which can be employed to deliver miRNAs effectively and safely to the target cells including the challenges associated with their development in particular emphasis on pulmonary diseases. Such approaches will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of miRNA delivery for pulmonary inflammatory diseases.

Novel Approaches in Formulation and Drug Delivery using Contact Lenses

PubMed Central

Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

2011-01-01

The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device PMID:24826007

Enterprise Systems (ES) Software in Business School Curriculum--Evaluation of Design and Delivery

ERIC Educational Resources Information Center

Seethamraju, Ravi

2007-01-01

Considering the increasing importance of enterprise systems in business, and their pedagogical value in demonstrating business process orientation and concepts of integration, several universities have incorporated popular enterprise system (ES) software products such as SAP R/3 into their business school curricula. This paper describes an attempt…

The Anaesthesia Gas Supply System

PubMed Central

Das, Sabyasachi; Chattopadhyay, Subhrajyoti; Bose, Payel

2013-01-01

The anaesthesia gas supply system is designed to provide a safe, cost-effective and convenient system for the delivery of medical gases at the point of-use. The doctrine of the anaesthesia gas supply system is based on four essential principles: Identity, continuity, adequacy and quality. Knowledge about gas supply system is an integral component of safe anaesthetic practice. Mishaps involving the malfunction or misuse of medical gas supply to operating theatres have cost many lives. The medical gases used in anaesthesia and intensive care are oxygen, nitrous oxide, medical air, entonox, carbon dioxide and heliox. Oxygen is one of the most widely used gases for life-support and respiratory therapy besides anaesthetic procedures. In this article, an effort is made to describe the production, storage and delivery of anaesthetic gases. The design of anaesthesia equipment must take into account the local conditions such as climate, demand and power supply. The operational policy of the gas supply system should have a backup plan to cater to the emergency need of the hospital, in the event of the loss of the primary source of supply. PMID:24249882

Design and Application of Multifunctional DNA Nanocarriers for Therapeutic Delivery

PubMed Central

Charoenphol, Phapanin; Bermudez, Harry

2013-01-01

The unique programmability of nucleic acids offers versatility and flexibility in the creation of self-assembled DNA nanostructures. To date, many three-dimensional DNA architectures have been precisely formed of varying sizes and shapes. Their biocompatibility, biodegradability, and high intrinsic stability in physiological environments emphasize their emerging use as carriers for drug and gene delivery. Furthermore, DNA nanocarriers have been shown to enter cells efficiently and without the aid of transfection reagents. A key strength of DNA nanocarriers over other delivery systems is their modularity and their ability to control the spatial distribution of cargoes and ligands. Optimizing DNA nanocarrier properties to dictate their localization, uptake, and intracellular trafficking is also possible. In this review, we present design considerations for DNA nanocarriers and examples of their use in the context of therapeutic delivery applications. The assembly of DNA nanocarriers and approaches for loading and releasing cargo are described. The stability and safety of DNA nanocarriers is also discussed, with particular attention to the in vivo physiological environment. Mechanisms of cellular uptake and intracellular trafficking are examined, and we conclude with strategies to enhance the delivery efficiency of DNA nanocarriers. PMID:23896566

Oral transmucosal delivery of naratriptan.

PubMed

Sattar, Mohammed; Lane, Majella E

2016-11-30

Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol ® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 ® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Patients with lower activation associated with higher costs; delivery systems should know their patients' 'scores'.

PubMed

Hibbard, Judith H; Greene, Jessica; Overton, Valerie

2013-02-01

Patient activation is a term that describes the skills and confidence that equip patients to become actively engaged in their health care. Health care delivery systems are turning to patient activation as yet another tool to help them and their patients improve outcomes and influence costs. In this article we examine the relationship between patient activation levels and billed care costs. In an analysis of 33,163 patients of Fairview Health Services, a large health care delivery system in Minnesota, we found that patients with the lowest activation levels had predicted average costs that were 8 percent higher in the base year and 21 percent higher in the first half of the next year than the costs of patients with the highest activation levels, both significant differences. What's more, patient activation was a significant predictor of cost even after adjustment for a commonly used "risk score" specifically designed to predict future costs. As health care delivery systems move toward assuming greater accountability for costs and outcomes for defined patient populations, knowing patients' ability and willingness to manage their health will be a relevant piece of information integral to health care providers' ability to improve outcomes and lower costs.

Grafting of steroids to hyaluronan towards the design of delivery systems for antioxidants: The role of hydrophobic core.

PubMed

Huerta-Ángeles, Gloria; Brandejsová, Martina; Novotný, Jaroslav; Kopecká, Kateřina; Šógorková, Jana; Šmejkalová, Daniela; Velebný, Vladimír

2018-08-01

In this work, amphiphilic hyaluronic acid (HA) was synthesized by the chemical bonding of steroids. Particularly, succinyl cholesterol (SCH), cholic acid (CA), deoxycholic acid (DOCA), and 18β-glycyrrhetinic acid (GA) were activated by benzoyl chloride towards the esterification reaction of HA in water. The degree of substitution can be controlled by varying the feed ratio of mixed anhydride to HA and up to 25% (mol/mol) can be obtained. Due to mild reaction conditions, no degradation of the polysaccharide was observed. The prepared amphiphilic polymers were characterized by NMR, infrared spectroscopy (FT-IR) and SEC/MALLS, as well as turbidity and size of the aggregates. The developed system is proposed for the delivery of hydrophobic drugs; for this purpose, curcumin, vitamin E and coenzyme Q10 were used as hydrophobic models; these molecules were loaded into the conjugates with high efficiency. The loading capacity was a function of degree of substitution. Furthermore, the biocompatibility of the derivatives and the cellular uptake of the delivery system enabled us to demonstrate the potential of the prepared delivery systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Protamine-based nanoparticles as new antigen delivery systems.

PubMed

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

2015-11-01

The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of mathematical modeling in sustained release delivery systems.

PubMed

Grassi, Mario; Grassi, Gabriele

2014-08-01

This review, presenting as starting point the concept of the mathematical modeling, is aimed at the physical and mathematical description of the most important mechanisms regulating drug delivery from matrix systems. The precise knowledge of the delivery mechanisms allows us to set up powerful mathematical models which, in turn, are essential for the design and optimization of appropriate drug delivery systems. The fundamental mechanisms for drug delivery from matrices are represented by drug diffusion, matrix swelling, matrix erosion, drug dissolution with possible recrystallization (e.g., as in the case of amorphous and nanocrystalline drugs), initial drug distribution inside the matrix, matrix geometry, matrix size distribution (in the case of spherical matrices of different diameter) and osmotic pressure. Depending on matrix characteristics, the above-reported variables may play a different role in drug delivery; thus the mathematical model needs to be built solely on the most relevant mechanisms of the particular matrix considered. Despite the somewhat diffident behavior of the industrial world, in the light of the most recent findings, we believe that mathematical modeling may have a tremendous potential impact in the pharmaceutical field. We do believe that mathematical modeling will be more and more important in the future especially in the light of the rapid advent of personalized medicine, a novel therapeutic approach intended to treat each single patient instead of the 'average' patient.

Liquid Crystalline Systems Based on Glyceryl Monooleate and Penetration Enhancers for Skin Delivery of Celecoxib: Characterization, In Vitro Drug Release, and In Vivo Studies.

PubMed

Dante, Mariane de Cássia Lima; Borgheti-Cardoso, Livia Neves; Fantini, Marcia Carvalho de Abreu; Praça, Fabíola Silva Garcia; Medina, Wanessa Silva Garcia; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

2018-03-01

Celecoxib (CXB) is a widely used anti-inflammatory drug that also acts as a chemopreventive agent against several types of cancer, including skin cancer. As the long-term oral administration of CXB has been associated with severe side effects, the skin delivery of this drug represents a promising alternative for the treatment of skin inflammatory conditions and chemoprevention of skin cancer. We prepared and characterized liquid crystalline systems based on glyceryl monooleate and water containing penetration enhancers which were primarily designed to promote skin delivery of CXB. Analysis of their phase behavior revealed the formation of cubic and hexagonal phases depending on the systems' composition. The systems' structure and composition markedly affected the in vitro CXB release profile. Oleic acid reduced CXB release rate, but association oleic acid/propylene glycol increased the drug release rate. The developed systems significantly reduced inflammation in an aerosil-induced rat paw edema model. The systems' composition and liquid crystalline structure influenced their anti-inflammatory potency. Cubic phase systems containing oleic acid/propylene glycol association reduced edema in a sustained manner, indicating that they modulate CXB release and permeation. Our findings demonstrate that the developed liquid crystalline systems are potential carriers for the skin delivery of CXB. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A real-time respiration position based passive breath gating equipment for gated radiotherapy: A preclinical evaluation

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

Hu Weigang; Xu Anjie; Li Guichao

2012-03-15

Purpose: To develop a passive gating system incorporating with the real-time position management (RPM) system for the gated radiotherapy. Methods: Passive breath gating (PBG) equipment, which consists of a breath-hold valve, a controller mechanism, a mouthpiece kit, and a supporting frame, was designed. A commercial real-time positioning management system was implemented to synchronize the target motion and radiation delivery on a linear accelerator with the patient's breathing cycle. The respiratory related target motion was investigated by using the RPM system for correlating the external markers with the internal target motion while using PBG for passively blocking patient's breathing. Six patientsmore » were enrolled in the preclinical feasibility and efficiency study of the PBG system. Results: PBG equipment was designed and fabricated. The PBG can be manually triggered or released to block or unblock patient's breathing. A clinical workflow was outlined to integrate the PBG with the RPM system. After implementing the RPM based PBG system, the breath-hold period can be prolonged to 15-25 s and the treatment delivery efficiency for each field can be improved by 200%-400%. The results from the six patients showed that the diaphragm motion caused by respiration was reduced to less than 3 mm and the position of the diaphragm was reproducible for difference gating periods. Conclusions: A RPM based PBG system was developed and implemented. With the new gating system, the patient's breath-hold time can be extended and a significant improvement in the treatment delivery efficiency can also be achieved.« less

DNA nanostructure-based drug delivery nanosystems in cancer therapy.

PubMed

Wu, Dandan; Wang, Lei; Li, Wei; Xu, Xiaowen; Jiang, Wei

2017-11-25

DNA as a novel biomaterial can be used to fabricate different kinds of DNA nanostructures based on its principle of GC/AT complementary base pairing. Studies have shown that DNA nanostructure is a nice drug carrier to overcome big obstacles existing in cancer therapy such as systemic toxicity and unsatisfied drug efficacy. Thus, different types of DNA nanostructure-based drug delivery nanosystems have been designed in cancer therapy. To improve treating efficacy, they are also developed into more functional drug delivery nanosystems. In recent years, some important progresses have been made. The objective of this review is to make a retrospect and summary about these different kinds of DNA nanostructure-based drug delivery nanosystems and their latest progresses: (1) active targeting; (2) mutidrug co-delivery; (3) construction of stimuli-responsive/intelligent nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

15 CFR 700.5 - Special priorities assistance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Overview § 700.5 Special priorities assistance. (a) The DPAS is designed to be largely self-executing. However, from time-to-time production or delivery problems will...

15 CFR 700.5 - Special priorities assistance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Overview § 700.5 Special priorities assistance. (a) The DPAS is designed to be largely self-executing. However, from time-to-time production or delivery problems will...

15 CFR 700.5 - Special priorities assistance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Overview § 700.5 Special priorities assistance. (a) The DPAS is designed to be largely self-executing. However, from time-to-time production or delivery problems will...

15 CFR 700.5 - Special priorities assistance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Overview § 700.5 Special priorities assistance. (a) The DPAS is designed to be largely self-executing. However, from time-to-time production or delivery problems will...

15 CFR 700.5 - Special priorities assistance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Overview § 700.5 Special priorities assistance. (a) The DPAS is designed to be largely self-executing. However, from time-to-time production or delivery problems will...

Multifunctional combinatorial-designed nanoparticles for nucleic acid therapy

NASA Astrophysics Data System (ADS)

Amiji, Mansoor M.

2016-05-01

Recent advances in biomedical sciences, especially in the field of human genetics, is increasingly considered to facilitate a new frontier in development of novel disease-modifying therapeutics. One of major challenges in the development of nucleic acid therapeutics is efficient and specific delivery of the molecules to the target tissue and cell upon systemic administration. In this report, I discuss our strategy to develop combinatorial-designed multifunctional nanoparticle assemblies based on natural biocompatible and biodegradable polymers for nucleic acid delivery in: (1) overcoming tumor drug resistance and (2) genetic modulation of macrophage functional phenotype from M1 to M2 in treatment of inflammatory diseases.

Simulation study of electric-guided delivery of 0.4µm monodisperse and polydisperse aerosols to the ostiomeatal complex.

PubMed

Xi, Jinxiang; Yuan, Jiayao Eddie; Si, Xiuhua April

2016-05-01

Despite the high prevalence of rhinosinusitis, current inhalation therapy shows limited efficacy due to extremely low drug delivery efficiency to the paranasal sinuses. Novel intranasal delivery systems are needed to enhance targeted delivery to the sinus with therapeutic dosages. An optimization framework for intranasal drug delivery was developed to target polydisperse charged aerosols to the ostiomeatal complex (OMC) with electric guidance. The delivery efficiency of a group of charged aerosols recently reported in the literature was numerically assessed and optimized in an anatomically accurate nose-sinus model. Key design variables included particle charge number, particle size and distribution, electrode strength, and inhalation velocity. Both monodisperse and polydisperse aerosol profiles were considered. Results showed that the OMC delivery efficiency was highly sensitive to the applied electric field and electrostatic charges carried by the particles. Through the synthesis of electric-guidance and point drug release, focused deposition with significantly enhanced dosage in the OMC can be achieved. For 0.4 µm charged aerosols, an OMC delivery efficiency of 51.6% was predicted for monodisperse aerosols and 34.4% for polydisperse aerosols. This difference suggested that the aerosol profile exerted a notable effect on intranasal deliveries. Sensitivity analysis indicated that the OMC deposition fraction was highly sensitive to the charge and size of particles and was less sensitive to the inhalation velocity considered in this study. Experimental studies are needed to validate the numerically optimized designs. Further studies are warranted to investigate the targeted OMC delivery with both electric and acoustics controls, the latter of which has the potential to further deliver the drug particles into the sinus cavity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validation Data for Mechanical System Algorithms Used in Building Energy Analysis Programs.

DTIC Science & Technology

1982-02-01

15 Zone Design 15 Built-Up Air Handler 15 Ventilation Requirements 16 The DES 16 Duct Design 17 Air -Delivery System 17 VAV Operation 17 Constant Volume...observed to operate well at reduced air flows, even at low flow in the so- called surge region. Recommendations 1. The HVAC system and component...With Inlet Guide Vanes Operating Within a Built-Up Air Handler 31 Test 2 -- Boiler Operation, Capacity, Efficiency, and Stand-By Losses 32 Test 3

Optimising probe holder design for sentinel lymph node imaging using clinical photoacoustic system with Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Sivasubramanian, Kathyayini; Periyasamy, Vijitha; Wen, Kew Kok; Pramanik, Manojit

2017-03-01

Photoacoustic tomography is a hybrid imaging modality that combines optical and ultrasound imaging. It is rapidly gaining attention in the field of medical imaging. The challenge is to translate it into a clinical setup. In this work, we report the development of a handheld clinical photoacoustic imaging system. A clinical ultrasound imaging system is modified to integrate photoacoustic imaging with the ultrasound imaging. Hence, light delivery has been integrated with the ultrasound probe. The angle of light delivery is optimized in this work with respect to the depth of imaging. Optimization was performed based on Monte Carlo simulation for light transport in tissues. Based on the simulation results, the probe holders were fabricated using 3D printing. Similar results were obtained experimentally using phantoms. Phantoms were developed to mimic sentinel lymph node imaging scenario. Also, in vivo sentinel lymph node imaging was done using the same system with contrast agent methylene blue up to a depth of 1.5 cm. The results validate that one can use Monte Carlo simulation as a tool to optimize the probe holder design depending on the imaging needs. This eliminates a trial and error approach generally used for designing a probe holder.

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

NASA Astrophysics Data System (ADS)

Guo, Zhen; Faghri, Amir

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

Development of a Delivery System for Treating Cerebrovascular Aneurysms Final Report CRADA No. TC-1440-97

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

Lee, A.; Derbin, J. T.

The objective of the project was to develop a system for delivering an implantable medical device used to treat cerebrovascular aneurysms, which can cause disability or hemorrhagic stroke (over 15,000 strokes in the U.S. each year are caused by ruptured aneurysms). Micrus has developed an implantable device with the potential to significantly improve the treatment of cerebrovascular aneurysms. This implantable device should significantly reduce the number of hemorrhagic strokes. LLNL has performed proof-of-concept experiments for a delivery system that could be modified to deploy the Micrus device into aneurysms. The purpose of this CRADA was to complete development of themore » LLNL delivery system and to integrate it with the Micrus device. The goal of the project was to develop an integrated minimally-invasive medical device for treating cerebrovascular aneurysms. The device was designed to access aneurysms through commercially-available catheters which are introduced into the patient through a small incision in the leg.« less

Beam delivery system with a non-digitized diffractive beam splitter for laser-drilling of silicon

NASA Astrophysics Data System (ADS)

Amako, J.; Fujii, E.

2016-02-01

We report a beam-delivery system consisting of a non-digitized diffractive beam splitter and a Fourier transform lens. The system is applied to the deep-drilling of silicon using a nanosecond pulse laser in the manufacture of inkjet printer heads. In this process, a circularly polarized pulse beam is divided into an array of uniform beams, which are then delivered precisely to the process points. To meet these requirements, the splitter was designed to be polarization-independent with an efficiency>95%. The optical elements were assembled so as to allow the fine tuning of the effective overall focal length by adjusting the wavefront curvature of the beam. Using the system, a beam alignment accuracy of<5 μm was achieved for a 12-mm-wide beam array and the throughput was substantially improved (10,000 points on a silicon wafer drilled in ~1 min). This beam-delivery scheme works for a variety of laser applications that require parallel processing.