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.

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) ...

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

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

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

Role of particle size, shape, and stiffness in design of intravascular drug delivery systems: insights from computations, experiments, and nature.

PubMed

Sen Gupta, Anirban

2016-01-01

Packaging of drug molecules within microparticles and nanoparticles has become an important strategy in intravascular drug delivery, where the particles are designed to protect the drugs from plasma effects, increase drug residence time in circulation, and often facilitate drug delivery specifically at disease sites. To this end, over the past few decades, interdisciplinary research has focused on developing biocompatible materials for particle fabrication, technologies for particle manufacture, drug formulation within the particles for efficient loading, and controlled release and refinement of particle surface chemistries to render selectivity toward disease site for site-selective action. Majority of the particle systems developed for such purposes are spherical nano and microparticles and they have had low-to-moderate success in clinical translation. To refine the design of delivery systems for enhanced performance, in recent years, researchers have started focusing on the physicomechanical aspects of carrier particles, especially their shape, size, and stiffness, as new design parameters. Recent computational modeling studies, as well as, experimental studies using microfluidic devices are indicating that these design parameters greatly influence the particles' behavior in hemodynamic circulation, as well as cell-particle interactions for targeted payload delivery. Certain cellular components of circulation are also providing interesting natural cues for refining the design of drug carrier systems. Based on such findings, new benefits and challenges are being realized for the next generation of drug carriers. The current article will provide a comprehensive review of these findings and discuss the emerging design paradigm of incorporating physicomechanical components in fabrication of particulate drug delivery systems. © 2015 Wiley Periodicals, Inc.

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

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…

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.

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

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.

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…

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.

MAST Propellant and Delivery System Design Methods

NASA Technical Reports Server (NTRS)

Nadeem, Uzair; Mc Cleskey, Carey M.

2015-01-01

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

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 Factors for Applying Cryogen Storage and Delivery Technology to Solar Thermal Propulsion

NASA Technical Reports Server (NTRS)

Millis, Marc G.

1996-01-01

Thermodynamic Vent System (TVS) and Multilayer Insulation (MLI) technology, originally developed for long term storage of cryogen propellants in microgravity, is ideally suited for propellant storage and delivery systems for solar thermal propulsion. With this technology the heat-induced pressure rise in the tank provides the propellant delivery pressure without the need for an auxiliary pressurant system, and propellant delivery is used to remove the excess heat to control tank pressure. The factors to consider in designing such a balanced system, are presented. An example of a minimum system design is presented along with examples of laboratory-tested hardware.

Structural design principles for delivery of bioactive components in nutraceuticals and functional foods.

PubMed

McClements, David Julian; Decker, Eric Andrew; Park, Yeonhwa; Weiss, Jochen

2009-06-01

There have been major advances in the design and fabrication of structured delivery systems for the encapsulation of nutraceutical and functional food components. A wide variety of delivery systems is now available, each with its own advantages and disadvantages for particular applications. This review begins by discussing some of the major nutraceutical and functional food components that need to be delivered and highlights the main limitations to their current utilization within the food industry. It then discusses the principles underpinning the rational design of structured delivery systems: the structural characteristics of the building blocks; the nature of the forces holding these building blocks together; and, the different ways of assembling these building blocks into structured delivery systems. Finally, we review the major types of structured delivery systems that are currently available to food scientists: lipid-based (simple, multiple, multilayer, and solid lipid particle emulsions); surfactant-based (simple micelles, mixed micelles, vesicles, and microemulsions) and biopolymer-based (soluble complexes, coacervates, hydrogel droplets, and particles). For each type of delivery system we describe its preparation, properties, advantages, and limitations.

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

20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

Code of Federal Regulations, 2013 CFR

2013-04-01

... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop...

20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

Code of Federal Regulations, 2014 CFR

2014-04-01

... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop...

20 CFR 662.430 - Under what conditions may One-Stop operators designated to operate in a One-Stop delivery system...

Code of Federal Regulations, 2012 CFR

2012-04-01

... designated to operate in a One-Stop delivery system established prior to the enactment of WIA be designated... (CONTINUED) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT One-Stop Operators § 662.430 Under what conditions may One-Stop operators designated to operate in a One-Stop...

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The design and scale-up of spray dried particle delivery systems.

PubMed

Al-Khattawi, Ali; Bayly, Andrew; Phillips, Andrew; Wilson, David

2018-01-01

The rising demand for pharmaceutical particles with tailored physicochemical properties has opened new markets for spray drying especially for solubility enhancement, improving inhalation medicines and stabilization of biopharmaceuticals. Despite this, the spray drying literature is scattered and often does not address the principles underpinning robust development of pharmaceuticals. It is therefore necessary to present clearer picture of the field and highlight the factors influencing particle design and scale-up. Areas covered: The review presents a systematic analysis of the trends in development of particle delivery systems using spray drying. This is followed by exploring the mechanisms governing particle formation in the process stages. Particle design factors including those of equipment configurations and feed/process attributes were highlighted. Finally, the review summarises the current industrial approaches for upscaling pharmaceutical spray drying. Expert opinion: Spray drying provides the ability to design particles of the desired functionality. This greatly benefits the pharmaceutical sector especially as product specifications are becoming more encompassing and exacting. One of the biggest barriers to product translation remains one of scale-up/scale-down. A shift from trial and error approaches to model-based particle design helps to enhance control over product properties. To this end, process innovations and advanced manufacturing technologies are particularly welcomed.

Design and Optimization of Floating Drug Delivery System of Acyclovir

PubMed Central

Kharia, A. A.; Hiremath, S. N.; Singhai, A. K.; Omray, L. K.; Jain, S. K.

2010-01-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t50%) and 70% (t70%) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t50% and t70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

Design and optimization of floating drug delivery system of acyclovir.

PubMed

Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K

2010-09-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

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.

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…

Rumen-stable delivery systems.

PubMed

Papas; Wu

1997-12-08

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

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

Stabilization challenges and formulation strategies associated with oral biologic drug delivery systems.

PubMed

Truong-Le, Vu; Lovalenti, Phillip M; Abdul-Fattah, Ahmad M

2015-10-01

Delivery of proteins to mucosal tissues of GI tract typically utilize formulations which protect against proteolysis and target the mucosal tissues. Using case studies from literature and the authors' own work, the in-process stability and solid state storage stability of biopharmaceuticals formulated in delivery systems designed for oral delivery to the GI tract will be reviewed. Among the range of delivery systems, biodegradable polymer systems for protection and controlled release of proteins have been the most studied; hence these systems will be covered in greater depth. These delivery systems include polymeric biodegradable microspheres or nanospheres that contain proteins or vaccines, which are designed to reduce the number of administrations/inoculations and the total protein dose required to achieve the desired biological effect. Specifically, this review will include a landscape survey of the systems that have been studied, the manufacturing processes involved, stability through the manufacturing process, key pharmaceutical formulation parameters that impact stability of the encased proteins, and storage stability of the encapsulated proteins in these delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

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

Design of liposomal colloidal systems for ocular delivery of ciprofloxacin

PubMed Central

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

2013-01-01

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

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.

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.

How can innovative project delivery systems improve the overall efficiency of GDOT in transportation project delivery?

DOT National Transportation Integrated Search

2013-04-01

The USDOT and Federal Highway Administration (FHWA) recommend the smart use of innovative project : delivery systems, such as design-build, to improve efficiency and effectiveness of developing transportation : projects. Although design-build provide...

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.

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…

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design.

PubMed

Rapolu, Kishore; Sanka, Krishna; Vemula, Praveen Kumar; Aatipamula, Vinaydas; Mohd, Abdul Bari; Diwan, Prakash V

2013-12-01

One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets. The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole. Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X1), sodium carboxy methylcellulose (X2) and NaHCO3 (X3). The dependent variables were floating lag time (YFLT), cumulative percentage of metronidazole released at 6th h (Y6) and cumulative percentage of metronidazole released at 12th h (Y12). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed. YFLT range was found to be from 1.02 to 12.07 min. The ranges of other responses, Y6 and Y12 were 25.72 ± 2.85 to 77.14 ± 3.42 % and 65.47 ± 1.25 to 99.65 ± 2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage. It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO3 can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.

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.

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.

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

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

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.

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.

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…

State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines.

PubMed

Dawidczyk, Charlene M; Kim, Chloe; Park, Jea Ho; Russell, Luisa M; Lee, Kwan Hyi; Pomper, Martin G; Searson, Peter C

2014-08-10

The ability to efficiently deliver a drug to a tumor site is dependent on a wide range of physiologically imposed design constraints. Nanotechnology provides the possibility of creating delivery vehicles where these design constraints can be decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing targeting efficiency and efficacy. Here we review the design strategies of the two FDA-approved antibody-drug conjugates (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and Abraxane) in the context of the challenges associated with systemic targeted delivery of a drug to a solid tumor. The lessons learned from these nanomedicines provide an important insight into the key challenges associated with the development of new platforms for systemic delivery of anti-cancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

Systems modelling and simulation in health service design, delivery and decision making.

PubMed

Pitt, Martin; Monks, Thomas; Crowe, Sonya; Vasilakis, Christos

2016-01-01

The ever increasing pressures to ensure the most efficient and effective use of limited health service resources will, over time, encourage policy makers to turn to system modelling solutions. Such techniques have been available for decades, but despite ample research which demonstrates potential, their application in health services to date is limited. This article surveys the breadth of approaches available to support delivery and design across many areas and levels of healthcare planning. A case study in emergency stroke care is presented as an exemplar of an impactful application of health system modelling. This is followed by a discussion of the key issues surrounding the application of these methods in health, what barriers need to be overcome to ensure more effective implementation, as well as likely developments in the future. 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/

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.

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.

Biomaterials for drug delivery systems.

PubMed

Buckles, R G

1983-01-01

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

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.

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.

Continuing Professional Education Delivery Systems.

ERIC Educational Resources Information Center

Weeks, James P.

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

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…

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

Adenosine-Associated Delivery Systems

PubMed Central

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

2016-01-01

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

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.

Colloidal drug delivery system: amplify the ocular delivery.

PubMed

Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

2016-01-01

The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

NASA Astrophysics Data System (ADS)

Mullen, Douglas Gurnett

Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules

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.

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.

Designing and developing suppository formulations for anti-HIV drug delivery.

PubMed

Ham, Anthony S; Buckheit, Robert W

2017-08-01

Despite a long history of use for rectal and vaginal drug delivery, the current worldwide market for suppositories is limited primarily due to a lack of user acceptability. Therefore, virtually no rational pharmaceutical development of antiviral suppositories has been performed. However, suppositories offer several advantages over other antiviral dosage forms. Current suppository designs have integrated active pharmaceutical ingredients into existing formulation designs without optimization. As such, emerging suppository development has been focused on improving upon the existing classical design to enhance drug delivery and is poised to open suppository drug delivery to a broader range of drugs, including antiretroviral products. Thus, with continuing research into rational suppository design and development, there is significant potential for antiretroviral suppository drug delivery.

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

MEMS: Enabled Drug Delivery Systems.

PubMed

Cobo, Angelica; Sheybani, Roya; Meng, Ellis

2015-05-01

Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multi-channel gas-delivery system

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

Rozenzon, Yan; Trujillo, Robert T.; Beese, Steven C.

One embodiment of the present invention provides a gas-delivery system for delivering reaction gas to a reactor chamber. The gas-delivery system includes a main gas-inlet port for receiving reaction gases and a gas-delivery plate that includes a plurality of gas channels. A gas channel includes a plurality of gas holes for allowing the reaction gases to enter the reactor chamber from the gas channel. The gas-delivery system further includes a plurality of sub-gas lines coupling together the main gas-inlet port and the gas-delivery plate, and a respective sub-gas line is configured to deliver a portion of the received reaction gasesmore » to a corresponding gas channel.« less

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.

Mucoadhesive drug delivery systems

PubMed Central

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

2011-01-01

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

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) ...

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.

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

PubMed

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

2016-01-30

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

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

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.

Design and Delivery of HMT Half-Shaft Prototype

DTIC Science & Technology

2012-11-01

spindle welded to the outer joint output is ease of Design  and Delivery of HMT Half‐ Shaft  Prototype    24    assembly. Flange 1 contains threaded... spindle , and splined shafts . Also, the spindle of the production design is splined to match the splines of the hub internals. 2.2. Analysis The...inner-joint (Figure 33). Design  and Delivery of HMT Half‐ Shaft  Prototype    27      Figure 33: FBD of Flange/ Spindle Applying Newton’s Laws to the

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.

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.

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.

Physically facilitating drug-delivery systems

PubMed Central

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

2012-01-01

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

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

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.

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

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.

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.

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.

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

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

PubMed

2005-03-01

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

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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

[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.

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.

Calcium silicate-based drug delivery systems.

PubMed

Zhu, Ying-Jie; Guo, Xiao-Xuan; Sham, Tsun-Kong

2017-02-01

Compared with other inorganic materials such as silica, metal oxides, noble metals and carbon, calcium silicate-based materials, especially nanostructured calcium silicate materials, have high biocompatibility, bioactivity and biodegradability, high specific surface area, nanoporous/hollow structure, high drug-loading capacity, pH-responsive drug release behavior and desirable drug release properties, and thus they are promising for the application in drug delivery. Calcium silicate-based drug delivery systems have a long drug-release time, which can significantly prolong the therapeutic effect of drugs. Another advantage of calcium silicate-based drug delivery systems is their pH-responsive drug release property, which can act as an ideal platform for targeted drug delivery. Areas covered: In recent years, studies have been carried out on calcium silicate-based drug delivery systems, and important results and insights have been documented. This article is not intended to offer a comprehensive review on the research on calcium silicate-based drug delivery systems, but presents some examples reported in the literature, and includes new insights obtained by tracking the interactions between drug molecules and calcium silicate carriers on the molecular level using the synchrotron-based X-ray spectroscopy. Expert opinion: Finally, our opinions on calcium silicate-based drug delivery systems are provided, and several research directions for the future studies are proposed.

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.

Design and evaluation of oral nanoemulsion drug delivery system of mebudipine.

PubMed

Khani, Samira; Keyhanfar, Fariborz; Amani, Amir

2016-07-01

A nanoemulsion drug delivery system was developed to increase the oral bioavailability of mebudipine as a calcium channel blocker with very low bioavailability profile. The impact of nano-formulation on the pharmacokinetic parameters of mebudipine in rats was investigated. Nanoemulsion formulations containing ethyl oleate, Tween 80, Span 80, polyethylene glycol 400, ethanol and deionized water were prepared using probe sonicator. The optimum formulation was evaluated for physicochemical properties, such as particle size, morphology and stability. The particle size of optimum formulation was 22.8 ± 4.0 nm. Based on the results of this study, the relative bioavailability of mebudipine nanoemulsion was enhanced by about 2.6-, 2.0- and 1.9-fold, respectively, compared with suspension, ethyl oleate solution and micellar solution. In conclusion, nanoemulsion is an interesting option for the delivery of poorly water soluble molecules, such as mebudipine.

A Systems Approach to Nitrogen Delivery

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

Goins, Bobby

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should bemore » less frustration associated with the delivery process.« less

Fiber coupled optical spark delivery system

DOEpatents

Yalin, Azer; Willson, Bryan; Defoort, Morgan

2008-08-12

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

Sterile Product Packaging and Delivery Systems.

PubMed

Akers, Michael J

2015-01-01

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

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.

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

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.

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

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.

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.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

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

2012-01-01

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

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

The new organization of the health care delivery system.

PubMed

Shortell, S M; Hull, K E

1996-01-01

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

Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

PubMed

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

2016-01-01

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

Design, Synthesis and Bio-evaluation of an EphA2-based Targeted Delivery System

PubMed Central

Barile, Elisa; Wang, Si; Das, Swadesh K.; Noberini, Roberta; Dahl, Russell; Stebbins, John L.; Pasquale, Elena B.; Fisher, Paul B.; Pellecchia, Maurizio

2014-01-01

We recently described a new targeted delivery system based on specific EphA2 receptor targeting peptides conjugated with the chemotherapeutic agent paclitaxel. In this manuscript we investigate the chemical determinants responsible for the stability and degradation of these agents in plasma. Introducing modifications in both the peptide and the linker between the peptide and paclitaxel, resulted in drug conjugates that are both long-lived in rat plasma and that markedly reduced tumor size in a prostate cancer xenograft model compared to paclitaxel alone treatment. These studies identify critical rate-limiting degradation sites on the peptide-drug conjugates, enabling the design of agents with increased stability and efficacy. These results provide support for our central hypothesis that peptide-drug conjugates targeting the EphA2 receptor represent an innovative and potentially effective strategy to selectively deliver cytotoxic drugs to cancer cells. PMID:24677792

Micelles As Delivery System for Cancer Treatment.

PubMed

Keskin, Dilek; Tezcaner, Aysen

2017-01-01

Micelles are nanoparticles formed by the self-assembly of amphiphilic block copolymers in certain solvents above concentrations called critical micelle concentration (CMC). Micelles are used in different fields like food, cosmetics, medicine, etc. These nanosized delivery systems are under spotlight in the recent years with new achievements in terms of their in vivo stability, ability to protect entrapped drug, release kinetics, ease of cellular penetration and thereby increased therapeutic efficacy. Drug loaded micelles can be prepared by dialysis, oil-in-water method, solid dispersion, freezing, spray drying, etc. The aim of this review is to give an overview of the research on micelles (in vitro, in vivo and clinical) as delivery system for cancer treatment. Passive targeting is one route for accumulation of nanosized micellar drug formulations. Many research groups from both academia and industry focus on developing new strategies for improving the therapeutic efficacy of micellar systems (active targeting to the tumor site, designing multidrug delivery systems for overcoming multidrug resistance or micelles formed by prodrug conjugates, etc). There is only one micellar drug formulation in South Korea that has reached clinical practice. However, there are many untargeted anticancer drug loaded micellar formulations in clinical trials, which have potential for use in clinics. Many more products are expected to be on the market in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Design and development of a freezer and chiller delivery box

NASA Astrophysics Data System (ADS)

Zakaria, Mohd Zakimi; Hung, Goh Chung; Dawi, Mohd Syedi Imran Mohd; Hussin, Radhwan; Khalil, Ahmad Nabil Mohd; Naim, Muhammad Khairy Md; Hilmi, Ahmad Humaizi

2017-09-01

This paper presents an action research of designed and fabricated using well insulating materials in order to ensure the coolness inside the freezer and chiller delivery box is as good minimize temperature raised. The main purpose of this study is to develop freeze and chiller delivery box that will be able to keep fresh meat during travelling long delivery. A range of freeze and chill solutions exists for that must be kept within a specific temperature range throughout the supply-and-distribution chain. This will help to minimize the activeness of bacteria to spoil the meats, at the same time it can linger the duration for meats to spoil. All affecting parameter such as temperature inside the delivery box, heat transfer rate, and natural convection flow pattern has been studied to design and development of the delivery box. Finally, temperature distribution analysis has been conducted which showed that in operating condition inside temperature are suitable to keep the fresh meats condition.

Radiation delivery system and method

DOEpatents

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

2002-01-01

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

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.

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

DOT National Transportation Integrated Search

2012-05-16

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

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…

Levodopa delivery systems: advancements in delivery of the gold standard.

PubMed

Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

2010-02-01

Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the

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.

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

PubMed

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

2006-12-11

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

Recent developments in leishmaniasis vaccine delivery systems.

PubMed

Bhowmick, Sudipta; Ali, Nahid

2008-07-01

The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

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.

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.

Design of a light delivery system for the photodynamic treatment of the Crohn's disease

NASA Astrophysics Data System (ADS)

Gabrecht, Tanja; Borle, Francois; van den Bergh, Hubert; Michetti, Pierre; Ortner, Maria-Anna; Wagnières, Georges

2007-07-01

Crohn's disease is an inflammatory bowel disease originating from an overwhelming response of the mucosal immune system. Low dose photodynamic therapy (PDT) may modify the mucosal immune response and thus serve as a therapy for Crohn's disease. Most patients with Crohn's disease show inflammatory reactions in the terminal ileum or colon where PDT treatment is feasible by low-invasive endoscopic techniques. However, the tube like geometry of the colon, it's folding, and the presences of multiple foci of Crohn's lesions along the colon require the development of adequate light delivery techniques. We present a prototype light delivery system for endoscopic clinical PDT in patients with Crohn's disease. The system is based on a cylindrical light diffuser inserted into a diffusing balloon catheter. Homogenous irradiation is performed with a 4 W diode laser at 635 nm. Light dosimetry is performed using a calibrated integrating sphere. The system can be used with conventional colonoscopes and colonovideoscopes having a 3.8 mm diameter working channel. The feasibility of PDT in colon with our prototype was demonstrated in first clinical trials.

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.

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

PubMed

Eddins, Blackberrie; Bell, Muyinatu A Lediju

2017-04-01

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

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

NASA Astrophysics Data System (ADS)

Eddins, Blackberrie; Bell, Muyinatu A. Lediju

2017-04-01

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

Design of minocycline-containing starch nanocapsules for topical delivery.

PubMed

Marto, J; Gouveia, L F; Gonçalves, L M; Ribeiro, H M; Almeida, A J

2018-06-11

Pharmaceutical research has been focused on developing improved delivery systems while exploring new ways of using approved excipients. The present work investigated the potential of starch nanocapsules (StNC) as a topical delivery platform for hydrophilic antimicrobial drugs using minocycline hydrochloride (MH) as a model drug. Thus, a quality by design approach was used to assess the role of different factors that affect the main pharmaceutical properties of StNC prepared using an emulsification-solvent evaporation method. Full characterization was performed in terms of particle size, encapsulation efficiency, morphology and physical stability at 5 ± 3°C. Results show the surfactant and lipid contents play a major role in StNC particle size distribution. The MH loading only promoted minor changes upon StNC properties. Formulations were stable without variations on physicochemical properties. All tested formulations presented a zeta potential of +33.6±6.7 mV, indicating a good physical stability and evidencing that StNC are suitable nanocarriers for topical use.

Design and in vitro evaluation of multiparticulate floating drug delivery system of zolpidem tartarate.

PubMed

Amrutkar, P P; Chaudhari, P D; Patil, S B

2012-01-01

Zolpidem tartarate is a non-benzodiazepine, sedative-hypnotic, which finds its major use in various types of insomnia. The present work relates to development of multiparticulate floating drug delivery system based on gas generation technique to prolong the gastric residence time and to increase the overall bioavailability. Modified release dosage form of zolpidem tartarate adapted to release over a predetermined time period, according to biphasic profile of dissolution, where the first phase is immediate release phase for inducing the sleep and the second phase is modified release phase for maintaining the sleep up to 10 h. The system consists of zolpidem tartarate layered pellets coated with effervescent layer and polymeric membrane. The floating ability and in vitro drug release of the system were dependent on amount of the effervescent agent (sodium bicarbonate) layered onto the drug layered pellets, and coating level of the polymeric membrane (Eudragit(®) NE 30D). The system could float completely within 5 min and maintain the floating over a period of 10 h. The multiparticulate floating delivery system of zolpidem tartarate with rapid floating and modified drug release was obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

Some engineering aspects of insulin delivery systems.

PubMed

Spencer, W J; Bair, R E; Carlson, G A; Love, J T; Urenda, R S; Eaton, R P; Schade, D S

1980-01-01

The characteristics of electronically controlled insulin delivery systems are presented. Early experiments with an external system have shown promise in providing improved glycemic control over conventional methods of single or multiple subcutaneous insulin injections. The encouraging results with external insulin delivery systems have led to the development and early testing in dogs of an implantable system with remote controls to permit variable insulin flow rates. A number of questions remain to be answered before widespread experimentation with external and implanted insulin delivery systems is possible. There appears to be no major development problems with the engineering aspects of such systems.

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.

Online course delivery modes and design methods in the radiologic sciences.

PubMed

Kowalczyk, Nina; Copley, Stacey

2013-01-01

To determine the current status of online education in the radiologic sciences and to explore learning management systems, course design methods, and online educational tools used in the radiologic sciences. A random sample of 373 educators from Joint Review Committee-accredited radiography, radiation therapy, and nuclear medicine technology educational programs was invited to participate in this study with an online survey. The majority of the programs responding to the survey do not offer online core courses. However, the institutions that do provide online core radiologic courses reported limited use of online tools for course delivery. BlackBoard was reported as the most commonly used learning management system. No significant relationships were identified in reference to self-reported instructor information technology self-efficacy and the instructors' age, years of teaching in higher education, years of teaching online, or use of asynchronous and synchronous technologies. Survey results did demonstrate a significant relationship between the type of institution and the use of synchronous technologies, suggesting that university-based programs were more likely to use this technology. Although the results suggest that online distance education is still not prevalent in radiologic science education, the past 3 years have seen a substantial increase in online course activity. This increase emphasizes the importance of adequate educator instruction and continuing education in the use of interactive technologies for online content delivery. Most educators report receiving 1 to 4 hours of training prior to online course implementation, but additional postimplementation training is necessary to improve the success of online delivery and further integrate interactive learning activities into an online format. The traditional classroom setting is still the primary course offering for radiologic science programs. PowerPoint remains the primary content delivery tool

Using DNA nanotechnology to produce a drug delivery system

NASA Astrophysics Data System (ADS)

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

2013-03-01

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

Preparation of pH-sensitive anionic liposomes designed for drug delivery system (DDS) application.

PubMed

Aoki, Asami; Akaboshi, Hikaru; Ogura, Taku; Aikawa, Tatsuo; Kondo, Takeshi; Tobori, Norio; Yuasa, Makoto

2015-01-01

We prepared pH-sensitive anionic liposomes composed solely of anionic bilayer membrane components that were designed to promote efficient release of entrapped agents in response to acidic pH. The pH-sensitive anionic liposomes showed high dispersion stability at neutral pH, but the fluidity of the bilayer membrane was enhanced in an acidic environment. These liposomes were rather simple and were composed of dimyristoylphosphatidylcholine (DMPC), an anionic bilayer membrane component, and polyoxyethylene sorbitan monostearate (Tween 80). In particular, the present pH-sensitive anionic liposomes showed higher temporal stability than those of conventional DMPC/DPPC liposomes. We found that pHsensitive properties strongly depended on the molecular structure, pKa value, and amount of an incorporated anionic bilayer membrane component, such as sodium oleate (SO), dimyristoylphosphatidylserine (DMPS), or sodium β-sitosterol sulfate (SS). These results provide an opportunity to manipulate liposomal stability in a pH-dependent manner, which could lead to the formulation of a high performance drug delivery system (DDS).

Micro injector sample delivery system for charged molecules

DOEpatents

Davidson, James C.; Balch, Joseph W.

1999-11-09

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

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.

Design of a potential colonic drug delivery system of mesalamine.

PubMed

Gohel, Mukesh C; Parikh, Rajesh K; Nagori, Stavan A; Dabhi, Mahesh R

2008-01-01

The aim of the present investigation was to develop a site-specific colonic drug delivery system, built on the principles of the combination of pH and time sensitivity. Press-coated mesalamine tablets with a coat of HPMC E-15 were over-coated with Eudragit S100. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2, 6.0, 7.2 and 6.4 mimicking different regions of gastrointestinal tract. The optimized batch (F2) showed less than 6% of drug release before reaching colonic pH 6.4 and complete drug release was obtained thereafter within 2 hr. A short-term dissolution stability study demonstrated statistical insignificant difference in drug release.

Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil.

PubMed

Villar, Ana Maria Sierra; Naveros, Beatriz Clares; Campmany, Ana Cristina Calpena; Trenchs, Monserrat Aróztegui; Rocabert, Coloma Barbé; Bellowa, Lyda Halbaut

2012-07-15

Self-nanoemulsifying drug delivery systems of gemfibrozil were developed under Quality by Design approach for improvement of dissolution and oral absorption. Preliminary screening was performed to select proper components combination. Box-Behnken experimental design was employed as statistical tool to optimize the formulation variables, X(1) (Cremophor(®) EL), X(2) (Capmul(®) MCM-C8), and X(3) (lemon essential oil). Systems were assessed for visual characteristics (emulsification efficacy), turbidity, droplet size, polydispersity index and drug release. Different pH media were also assayed for optimization. Following optimization, the values of formulation components (X(1), X(2), and X(3)) were 32.43%, 29.73% and 21.62%, respectively (16.22% of gemfibrozil). Transmission electron microscopy demonstrated spherical droplet morphology. SNEEDS release study was compared to commercial tablets. Optimized SNEDDS formulation of gemfibrozil showed a significant increase in dissolution rate compared to conventional tablets. Both formulations followed Weibull mathematical model release with a significant difference in t(d) parameter in favor of the SNEDDS. Equally amodelistic parameters were calculated being the dissolution efficiency significantly higher for SNEDDS, confirming that the developed SNEDDS formulation was superior to commercial formulation with respect to in vitro dissolution profile. This paper provides an overview of the SNEDDS of the gemfibrozil as a promising alternative to improve oral absorption. Copyright © 2012 Elsevier B.V. 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.

Fiber laser coupled optical spark delivery system

DOEpatents

Yalin, Azer [Fort Collins, CO; Willson, Bryan [Fort Collins, CO; Defoort, Morgan [Fort Collins, CO; Joshi, Sachin [Fort Collins, CO; Reynolds, Adam [Fort Collins, CO

2008-03-04

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

The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery.

PubMed

Shorter, Susan A; Gollings, Alexander S; Gorringe-Pattrick, Monique A M; Coakley, J Emma; Dyer, Paul D R; Richardson, Simon C W

2017-05-01

The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for 'drug' delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the 'PEG dilemma', balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem. Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking. Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic 'helpers' or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic.

Bespoke program design for school-aged therapy disability service delivery.

PubMed

Weatherill, Pamela; Bahn, Susanne; Cooper, Trudi

2012-01-01

This article uses the evaluation of a school-aged therapy service for children with disabilities in Western Australia to investigate models of service delivery. The current literature on family-centered practice, multidisciplinary and transdisciplinary approaches, and 4 models of service are reviewed. The models include the life needs model, the relational goal-orientated model of optimal service delivery to children and families, the quality of life model, and the collaborative model of service delivery. Analysis of the data is presented together with a bespoke model of service delivery for children with disabilities, arguing that local contexts benefit from custom-made service design.

Status of Statewide Career Information Delivery Systems.

ERIC Educational Resources Information Center

Dunn, Wynonia L.

Intended as a resource document as well as a status report on all the statewide career information delivery systems (CIDS) in operation, this report examines the status of 39 statewide information systems. (Career information delivery systems are computer-based systems that provide national, state, and local information to individuals who are in…

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.

Planetary Regolith Delivery Systems for ISRU

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

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.

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/.

Modeling the Delivery Physiology of Distributed Learning Systems.

ERIC Educational Resources Information Center

Paquette, Gilbert; Rosca, Ioan

2003-01-01

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

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.

Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone.

PubMed

Iurian, Sonia; Turdean, Luana; Tomuta, Ioan

2017-01-01

This study focuses on the development of a drug product based on a risk assessment-based approach, within the quality by design paradigm. A prolonged release system was proposed for paliperidone (Pal) delivery, containing Kollidon ® SR as an insoluble matrix agent and hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), or sodium carboxymethyl cellulose as a hydrophilic polymer. The experimental part was preceded by the identification of potential sources of variability through Ishikawa diagrams, and failure mode and effects analysis was used to deliver the critical process parameters that were further optimized by design of experiments. A D-optimal design was used to investigate the effects of Kollidon SR ratio ( X 1 ), the type of hydrophilic polymer ( X 2 ), and the percentage of hydrophilic polymer ( X 3 ) on the percentages of dissolved Pal over 24 h ( Y 1 - Y 9 ). Effects expressed as regression coefficients and response surfaces were generated, along with a design space for the preparation of a target formulation in an experimental area with low error risk. The optimal formulation contained 27.62% Kollidon SR and 8.73% HPMC and achieved the prolonged release of Pal, with low burst effect, at ratios that were very close to the ones predicted by the model. Thus, the parameters with the highest impact on the final product quality were studied, and safe ranges were established for their variations. Finally, a risk mitigation and control strategy was proposed to assure the quality of the system, by constant process monitoring.

Healthcare delivery systems: designing quality into health information systems.

PubMed

Joyce, Phil; Green, Rosamund; Winch, Graham

2007-01-01

To ensure that quality is 'engineered in' a holistic, integrated and quality approach is required, and Total Quality Management (TQM) principles are the obvious foundations for this. This paper describes a novel approach to viewing the operations of a healthcare provider where electronic means could be used to distribute information (including electronic fund settlements), building around the Full Service Provider core. Specifically, an approach called the "triple pair flow" model is used to provide a view of healthcare delivery that is integrated, yet detailed, and that combines the strategic enterprise view with a business process view.

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

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

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.

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.

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

Advanced Drug Delivery Systems for Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs: A Review.

PubMed

Kumar, Lalit; Verma, Shivani; Singh, Mehakjot; Tamanna, Tamanna; Utreja, Puneet

2018-06-04

Transdermal route of delivery of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has several advantages over other routes like reduced adverse effects, less systemic absorption, and avoidance of first pass effect and degradation in the gastrointestinal tract (GIT). Transdermal route is also beneficial for drugs having a narrow therapeutic index. The skin acts as the primary barrier for transdermal delivery of various therapeutic molecules. Various advanced nanocarrier systems offer several advantages like improved dermal penetration along with an extended drug release profile due to their smaller size and high surface area. Various nanocarrier explored for transdermal delivery of NSAIDs are liposomes, niosomes, ethosomes, polymeric nanoparticles (NPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), dendrimers, nanosuspensions/nanoemulsion, and nanofibers Objectives: In the present review, our major aim was to explore the therapeutic potential of advanced nanocarrier systems enlisted above for transdermal delivery of NSAIDs. All literature search regarding advanced nanocarrier systems for transdermal delivery of NSAIDs was done using Google Scholar and Pubmed. Advanced nanocarrier have shown various advantages like reduced side effect, low dosing frequency, high skin permeation, and ease of application over conventional transdermal delivery systems of NSAIDs in various preclinical studies. However, clinical exploration of advanced nanocarrier systems for transdermal delivery of NSAIDs is still a challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

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.

Mucoadhesive and thermogelling systems for vaginal drug delivery.

PubMed

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

2015-09-15

This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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

PubMed

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

2017-02-14

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

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;…

Advances in bioresponsive closed-loop drug delivery systems.

PubMed

Yu, Jicheng; Zhang, Yuqi; Yan, Junjie; Kahkoska, Anna R; Gu, Zhen

2017-11-27

Controlled drug delivery systems are able to improve efficacy and safety of therapeutics by optimizing the duration and kinetics of release. Among them, closed-loop delivery strategies, also known as self-regulated administration, have proven to be a practical tool for homeostatic regulation, by tuning drug release as a function of biosignals relevant to physiological and pathological processes. A typical example is glucose-responsive insulin delivery system, which can mimic the pancreatic beta cells to release insulin with a proper dose at a proper time point by responding to plasma glucose levels. Similar self-regulated systems are also important in the treatment of other diseases including thrombosis and bacterial infection. In this review, we survey the recent advances in bioresponsive closed-loop drug delivery systems, including glucose-responsive, enzyme-activated, and other biosignal-mediated delivery systems. We also discuss the future opportunities and challenges in this field. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances of blood cell-based drug delivery systems.

PubMed

Sun, Yanan; Su, Jing; Liu, Geyi; Chen, Jianjun; Zhang, Xiumei; Zhang, Ran; Jiang, Minhan; Qiu, Mingfeng

2017-01-01

Blood cells, including erythrocytes, leukocytes and platelets are used as drug carriers in a wide range of applications. They have many unique advantages such as long life-span in circulation (especially erythrocytes), target release capacities (especially platelets), and natural adhesive properties (leukocytes and platelets). These properties make blood cell based delivery systems, as well as their membrane-derived carriers, far superior to other drug delivery systems. Despite the advantages, the further development of blood cell-based delivery systems was hindered by limitations in the source, storage, and mass production. To overcome these problems, synthetic biomaterials that mimic blood cell and nanocrystallization of blood cells have been developed and may represent the future direction for blood cell membrane-based delivery systems. In this paper, we review recent progress of the rising blood cell-based drug delivery systems, and also discuss their challenges and future tendency of development. Copyright © 2016. Published by Elsevier B.V.

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.

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

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.

A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.

PubMed

Wu, Ping; Liang, Qin; Feng, Pei; Li, Chunyan; Yang, Chunguang; Liang, Hongsuo; Tang, Huaibo; Shuai, Cijun

2017-04-03

The seeds of Strychnos nux -vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnos nux - vomica . Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.

A telemedicine health care delivery system

NASA Technical Reports Server (NTRS)

Sanders, Jay H.

1991-01-01

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

Design and evaluation of self-emulsifying drug delivery systems of Rhizoma corydalis decumbentis extracts.

PubMed

Ma, Hongda; Zhao, Qingchun; Wang, Yongjun; Guo, Tao; An, Ye; Shi, Guobing

2012-10-01

To improve the dissolution and oral absorption of Rhizoma corydalis decumbentis extracts (RCDE), a famous traditional Chinese herbal medicine which contains poorly water-soluble active components, self-emulsifying drug-delivery systems (SEDDS) were designed and evaluated in vitro and in vivo for the first time. Six formulations were prepared, and pseudoternary phase diagrams were constructed to identify the efficient self-emulsication region through the modified visual test. The optimized formulation consisted of 45% Solutol, 40% ethyl oleate, and 15% Transcutol P. The mean droplet size distribution of the optimized SEDDS was less than 100 nm. The release of the active components (protopine and tetrahydropalmatine) in RCDE from SEDDS hard gelatin capsules showed a faster rate in comparison with the commercial tablets. After oral administration of RCDE SEDDS capsules or the commercial tablets to fasted rats, the relative bioavailability of SEDDS capsules for protopine and tetrahydropalmatine was 209.7% and 133.2% compared with commercial tablets, respectively. Our study indicated that SEDDS has the potential to improve the bioavailability of traditional Chinese medicines, in which many active components are hydrophobic, such as RCDE.

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.

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 (system could replace a chemical battery in an implantable system, eliminating the risks associated with battery failure and leakage and also allowing more compact designs for applications such as drug delivery.

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

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

PubMed

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

2016-07-30

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

Technological Delivery Systems.

ERIC Educational Resources Information Center

Kennedy, Don; And Others

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

Delivery System, 2003-2004.

ERIC Educational Resources Information Center

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

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

Drug Delivery and Nanoformulations for the Cardiovascular System.

PubMed

Geldenhuys, W J; Khayat, M T; Yun, J; Nayeem, M A

2017-02-01

Therapeutic delivery to the cardiovascular system may play an important role in the successful treatment of a variety of disease state, including atherosclerosis, ischemic-reperfusion injury and other types of microvascular diseases including hypertension. In this review we evaluate the different options available for the development of suitable delivery systems that include the delivery of small organic compounds [adenosin A 2A receptor agonist (CGS 21680), CYP-epoxygenases inhibitor (N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide, trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy] benzoic acid), soluble epoxide hydrolase inhibitor (N-methylsulfonyl-12,12-dibromododec-11-enamide), PPARγ agonist (rosiglitazone) and PPARγ antagonist (T0070907)], nanoparticles, peptides, and siRNA to the cardiovascular system. Effective formulations of nanoproducts have significant potential to overcome physiological barriers and improve therapeutic outcomes in patients. As per the literature covering targeted delivery to the cardiovascular system, we found that this area is still at infancy stage, as compare to the more mature fields of tumor cancer or brain delivery (e.g. blood-brain barrier permeability) with fewer publications focused on the targeted drug delivery technologies. Additionally, we show how pharmacology needs to be well understood when considering the cardiovascular system. Therefore, we discussed in this review various receptors agonists, antagonists, activators and inhibitors which will have effects on cardiovascular system.

Light-switchable systems for remotely controlled drug delivery.

PubMed

Shim, Gayong; Ko, Seungbeom; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Lee, Jaiwoo; Kwon, Taekhyun; Choi, Han-Gon; Kim, Young Bong; Oh, Yu-Kyoung

2017-12-10

Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines. We need a paradigm shift in drug delivery. One strategy that may overcome the limitations of pathophysiology-based drug delivery is the use of remotely controlled delivery technology. Unlike pathophysiology-based active drug targeting strategies, light-switchable systems are not affected by the heterogeneity of cells, tissue types, and/or microenvironments. Instead, they are triggered by remote light (i.e., near-infrared) stimuli, which are absorbed by photoresponsive molecules or three-dimensional nanostructures. The sequential conversion of light to heat or reactive oxygen species can activate drug release and allow it to be spatio-temporally controlled. Light-switchable systems have been used to activate endosomal drug escape, modulate the release of chemical and biological drugs, and alter nanoparticle structures to control the release rates of drugs. This review will address the limitations of pathophysiology-based drug delivery systems, the current status of light-based remote-switch systems, and future directions in the application of light-switchable systems for remotely controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Principles of nanoparticle design for overcoming biological barriers to drug delivery

PubMed Central

Blanco, Elvin; Shen, Haifa; Ferrari, Mauro

2016-01-01

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery. PMID:26348965

Gantries and dose delivery systems

NASA Astrophysics Data System (ADS)

Meer, David; Psoroulas, Serena

2015-06-01

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

Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone

PubMed Central

Iurian, Sonia; Turdean, Luana; Tomuta, Ioan

2017-01-01

This study focuses on the development of a drug product based on a risk assessment-based approach, within the quality by design paradigm. A prolonged release system was proposed for paliperidone (Pal) delivery, containing Kollidon® SR as an insoluble matrix agent and hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), or sodium carboxymethyl cellulose as a hydrophilic polymer. The experimental part was preceded by the identification of potential sources of variability through Ishikawa diagrams, and failure mode and effects analysis was used to deliver the critical process parameters that were further optimized by design of experiments. A D-optimal design was used to investigate the effects of Kollidon SR ratio (X1), the type of hydrophilic polymer (X2), and the percentage of hydrophilic polymer (X3) on the percentages of dissolved Pal over 24 h (Y1–Y9). Effects expressed as regression coefficients and response surfaces were generated, along with a design space for the preparation of a target formulation in an experimental area with low error risk. The optimal formulation contained 27.62% Kollidon SR and 8.73% HPMC and achieved the prolonged release of Pal, with low burst effect, at ratios that were very close to the ones predicted by the model. Thus, the parameters with the highest impact on the final product quality were studied, and safe ranges were established for their variations. Finally, a risk mitigation and control strategy was proposed to assure the quality of the system, by constant process monitoring. PMID:28331293

Deep Space Systems Technology Program Future Deliveries

NASA Technical Reports Server (NTRS)

Salvo, Christopher G.; Keuneke, Matthew S.

2000-01-01

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

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.

Microneedles As a Delivery System for Gene Therapy

PubMed Central

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

2016-01-01

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

Joint Cross-Layer Design for Wireless QoS Content Delivery

NASA Astrophysics Data System (ADS)

Chen, Jie; Lv, Tiejun; Zheng, Haitao

2005-12-01

In this paper, we propose a joint cross-layer design for wireless quality-of-service (QoS) content delivery. Central to our proposed cross-layer design is the concept of adaptation. Adaptation represents the ability to adjust protocol stacks and applications to respond to channel variations. We focus our cross-layer design especially on the application, media access control (MAC), and physical layers. The network is designed based on our proposed fast frequency-hopping orthogonal frequency division multiplex (OFDM) technique. We also propose a QoS-awareness scheduler and a power adaptation transmission scheme operating at both the base station and mobile sides. The proposed MAC scheduler coordinates the transmissions of an IP base station and mobile nodes. The scheduler also selects appropriate transmission formats and packet priorities for individual users based on current channel conditions and the users' QoS requirements. The test results show that our cross-layer design provides an excellent framework for wireless QoS content delivery.

Finasteride topical delivery systems for androgenetic alopecia.

PubMed

Khan, Muhammad Zia Ullah; Khan, Shujaat Ali; Ubaid, Muhammad; Shah, Aamna; Kousar, Rozina; Murtaza, Ghulam

2018-01-23

Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of sexual disorders including decrease in libido, gynecomastia, erectile dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since, hair follicles widely home in 5α-reductase, topical formulations of finasteride in comparison to its oral formulations are expected to potentially reduce its systemic adverse effects. The analysis of literature has revealed some delivery systems developed for the enhanced and localized penetration of finasteride into the skin. These finasteride delivery systems include polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim of this review article is to briefly amass all literature on topical delivery of finasteride to elaborate best dosage form, i.e. formulation having maximum permeation rate. This study will serve as a future perspective regarding topical delivery of finasteride. The literature analysis has exhibited that most of the previous investigators have used propylene glycol in their finasteride-loaded topical formulations, while poloxamer P407, monoolein, transcutol P and choline was used in few formulations. Moreover among all drug delivery systems, finasteride liposomal gel system consisting of 2% methyl cellulose and gel system containing poloxamer P407 exhibited the highest flux with a value of 28.4 ± 1.3 µg/cm2h and 23.1 ± 1.4 µg/cm2h, respectively. Several topical drug delivery techniques such as topical microneedles, aerosol foams, nanoemulsions, microsponges, and emulsifier free formulations, fullerenes

Superparamagnetic Iron Oxide Nanoparticle-Based Delivery Systems for Biotherapeutics

PubMed Central

Mok, Hyejung; Zhang, Miqin

2014-01-01

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

Optical diagnostics integrated with laser spark delivery system

DOEpatents

Yalin, Azer [Fort Collins, CO; Willson, Bryan [Fort Collins, CO; Defoort, Morgan [Fort Collins, CO; Joshi, Sachin [Fort Collins, CO; Reynolds, Adam [Fort Collins, CO

2008-09-02

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

Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

PubMed

Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

2016-01-01

Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

Convection-enhanced delivery to the central nervous system.

PubMed

Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

2015-03-01

Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

Classification of stimuli-responsive polymers as anticancer drug delivery systems.

PubMed

Taghizadeh, Bita; Taranejoo, Shahrouz; Monemian, Seyed Ali; Salehi Moghaddam, Zoha; Daliri, Karim; Derakhshankhah, Hossein; Derakhshani, Zaynab

2015-02-01

Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.

On prilled Nanotubes-in-Microgel Oral Systems for protein delivery.

PubMed

de Kruif, Jan Kendall; Ledergerber, Gisela; Garofalo, Carla; Fasler-Kan, Elizaveta; Kuentz, Martin

2016-04-01

Newly discovered active macromolecules are highly promising for therapy, but poor bioavailability hinders their oral use. Microencapsulation approaches, such as protein prilling into microspheres, may enable protection from gastrointestinal (GI) enzymatic degradation. This would increase bioavailability mainly for local delivery to GI lumen or mucosa. This work's purpose was to design a novel architecture, namely a Nanotubes-in-Microgel Oral System, by prilling for protein delivery. Halloysite nanotubes (HNT) were selected as orally acceptable clay particles and their lumen was enlarged by alkaline etching. This chemical modification increased the luminal volume to a mean of 216.3 μL g(-1) (+40.8%). After loading albumin as model drug, the HNT were entrapped in microgels by prilling. The formation of Nanoparticles-in-Microsphere Oral System (NiMOS) yielded entrapment efficiencies up to 63.2%. NiMOS shape was spherical to toroidal, with a diameter smaller than 320 μm. Release profiles depended largely on the employed system and HNT type. Protein stability was determined throughout prilling and after in vitro enzymatic degradation. Prilling did not harm protein structure, and NiMOS demonstrated higher enzymatic protection than pure nanotubes or microgels, since up to 82% of BSA remained unscathed after in vitro digestion. Therefore, prilled NiMOS was shown to be a promising and flexible multi-compartment system for oral (local) macromolecular delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Veggie Passive Orbital Nutrient Delivery System (PONDS)

NASA Image and Video Library

2018-02-27

Project scientists, place seeds in Veggie Passive Orbital Nutrient Delivery System (PONDS) units inside a laboratory at the Space Station Processing Facility at NASA’s Kennedy Space Center in Florida. Veggie PONDS is a direct follow-on to the Veg-01 and Veg-03 hardware and plant growth validation tests. The primary goal of this newly developed plant growing system, Veggie PONDS, is to demonstrate uniform plant growth. PONDS units have features that are designed to mitigate microgravity effects on water distribution, increase oxygen exchange and provide sufficient room for root zone growth. PONDS is planned for use during Veg-04 and Veg-05 on the International Space Station after the Veggie PONDS Validation flights on SpaceX-14 and OA-9.

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

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.

Enterprise networks. Strategies for integrated delivery systems.

PubMed

Siwicki, B

1997-02-01

More integrated delivery systems are making progress toward building computer networks that link all their care delivery sites so they can efficiently and economically coordinate care. A growing number of these systems are turning to intranets--private computer networks that use Internet-derived protocols and technologies--to move information that's essential to managing scare health care resources.

Development of the Choctaw Health Delivery System.

ERIC Educational Resources Information Center

Nguyen, Binh N.

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

Emerging potential of stimulus-responsive nanosized anticancer drug delivery systems for systemic applications.

PubMed

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Madeshwaran, Thiagarajan; Hiep, Tran Tuan; Kandasamy, Umadevi; Oh, Kyung Taek; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2018-02-01

The development of novel drug delivery systems based on well-defined polymer therapeutics has led to significant improvements in the treatment of multiple disorders. Advances in material chemistry, nanotechnology, and nanomedicine have revolutionized the practices of drug delivery. Stimulus-responsive material-based nanosized drug delivery systems have remarkable properties that allow them to circumvent biological barriers and achieve targeted intracellular drug delivery. Specifically, the development of novel nanocarrier-based therapeutics is the need of the hour in managing complex diseases. In this review, we have briefly described the fundamentals of drug targeting to diseased tissues, physiological barriers in the human body, and the mechanisms/modes of drug-loaded carrier systems. To that end, this review serves as a comprehensive overview of the recent developments in stimulus-responsive drug delivery systems, with focus on their potential applications and impact on the future of drug delivery.

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

Self-emulsifying drug delivery systems: Design of a novel vaginal delivery system for curcumin.

PubMed

Köllner, S; Nardin, I; Markt, R; Griesser, J; Prüfert, F; Bernkop-Schnürch, A

2017-06-01

The aim of this study was to develop a vaginal self-emulsifying delivery system for curcumin being capable of spreading, of permeating the mucus gel layer and of protecting the drug being incorporated in oily nanodroplets towards mucus interactions and immobilization. The emulsifying properties of curcumin loaded SEDDS containing 30% Cremophor RH40, 20% Capmul PG-8, 30% Captex 300, 10% DMSO and 10% tetraglycol (SEDD formulation A) as well as 25% PEG 200, 35% Cremophor RH40, 20% Captex 355, 10% Caprylic acid and 10% Tween 80 (SEDD formulation B) after diluting 1+2 with artificial vaginal fluid were characterized regarding droplet size and zeta potential. Collagen swelling test was used to examine the irritation potential of SEDDS. Additionally to mucus binding studies, permeation studies in the mucus were performed. Furthermore, spreading potential of the novel developed formulations was compared with a commercial available o/w cream (non-ionic hydrophilic cream) on vaginal mucosa. SEDDS displayed a mean droplet size between 38 and 141nm and a zeta potential of -0.3 to -1.6mV. The collagen swelling test indicated no significant irritation potential of both formulations over 24h. An immediate interaction of unformulated curcumin with the mucus was determined, whereas both SEDDS facilitated drug permeation through the mucus layer. Formulation B showed a 2.2-fold improved transport ratio of curcumin compared to SEDD formulation A. In comparison to the vaginal cream, SEDD formulation A and B were able to spread over the vaginal mucosa and cover the tissue to a 17.8- and 14.8-fold higher extent, respectively. According to these results, SEDDS seems to be a promising tool for vaginal application. Copyright © 2017 Elsevier B.V. All rights reserved.

Distance Synchronous Information Systems Course Delivery

ERIC Educational Resources Information Center

Peslak, Alan R.; Lewis, Griffith R.; Aebli, Fred

2014-01-01

Teaching computer information systems via distance education is a challenge for both student and faculty. Much research work has been performed on methods of teaching via distance education. Today we are faced with a variety of options for course delivery. Asynchronous delivery via online or lesson instruction still remains most common. But…

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.

Polymer nanogels: a versatile nanoscopic drug delivery platform

PubMed Central

Chacko, Reuben T.; Ventura, Judy; Zhuang, Jiaming; Thayumanavan, S.

2012-01-01

In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed. PMID:22342438

Nano drug delivery systems and gamma radiation sterilization.

PubMed

Sakar, F; Özer, A Y; Erdogan, S; Ekizoglu, M; Kart, D; Özalp, M; Colak, S; Zencir, Y

2017-09-01

In recent years, drug delivery systems such as liposomes and microparticles have been used in clinic for the treatment of different diseases and from a regulatory point of view, a parenterally applied drug and drug delivery systems must be sterile and pyrogen free. Radiation sterilization is a method recognized by pharmacopoeias to achieve sterility criteria of parenterals. It has the ability to kill microorganisms in therapeutic products. The ability of, however, irradiation might also affect the performance of drug delivery systems. One of the most critical points is irradiation dose, because certain undesirable chemical and physical changes may accompany with the irradiation, especially with the traditionally applied dose of 25 kGy. Its ionizing property may cause fragmentation of covalent bond. The care must be paid to the applied dose. In this research, the effects of gamma irradiation on different drug delivery systems such as chitosan microparticles, liposomes, niosomes and sphingosomes were investigated. According to the experimental data, it can be concluded that gamma irradiation can be a suitable sterilization technique for liposome, niosome and sphingosome dispersions. When all irradiated drug carrier systems were taken into consideration, chitosan glutamate microparticles were found as the most radioresistant drug delivery system among the others.

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.

System-based approach for an advanced drug delivery platform

NASA Astrophysics Data System (ADS)

Kulinsky, Lawrence; Xu, Han; Tsai, Han-Kuan A.; Madou, Marc

2006-03-01

Present study is looking at the problem of integrating drug delivery microcapsule, a bio-sensor, and a control mechanism into a biomedical drug delivery system. A wide range of medical practices from cancer therapy to gastroenterological treatments can benefit from such novel bio-system. Drug release in our drug delivery system is achieved by electrochemically actuating an array of polymeric valves on a set of drug reservoirs. The valves are bi-layer structures, made in the shape of a flap hinged on one side to a valve seat, and consisting of thin films of evaporated gold and electrochemically deposited polypyrrole (PPy). These thin PPy(DBS) bi-layer flaps cover access holes of underlying chambers micromachined in a silicon substrate. Chromium and polyimide layers are applied to implement "differential adhesion" to obtain a voltage induced deflection of the bilayer away from the drug reservoir. The Cr is an adhesion-promoting layer, which is used to strongly bind the gold layer down to the substrate, whereas the gold adheres weakly to polyimide. Drug actives (dry or wet) were pre-stored in the chambers and their release is achieved upon the application of a small bias (~ 1V). Negative voltage causes cation adsorption and volume change in PPy film. This translates into the bending of the PPy/Au bi-layer actuator and release of the drug from reservoirs. This design of the drug delivery module is miniaturized to the dimensions of 200μm valve diameter. Galvanostatic and potentiostatic PPy deposition methods were compared, and potentiostatic deposition method yields film of more uniform thickness. PPy deposition experiments with various pyrrole and NaDBS concentrations were also performed. Glucose biosensor based on glucose oxidase (GOx) embedded in the PPy matrix during elechtrochemical deposition was manufactured and successfully tested. Multiple-drug pulsatile release and continuous linear release patterns can be implemented by controlling the operation of an array

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.

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

PubMed Central

Upadhyay, Ravi Kant

2014-01-01

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

Non-coding RNAs: Therapeutic Strategies and Delivery Systems.

PubMed

Ling, Hui

The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer.

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.

Peptide/protein vaccine delivery system based on PLGA particles.

PubMed

Allahyari, Mojgan; Mohit, Elham

2016-03-03

Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted.

Peptide/protein vaccine delivery system based on PLGA particles

PubMed Central

Allahyari, Mojgan; Mohit, Elham

2016-01-01

abstract Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

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.

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.

Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal peptide drug delivery system.

PubMed

Langoth, Nina; Kahlbacher, Hermann; Schöffmann, Gudrun; Schmerold, Ivo; Schuh, Maximilian; Franz, Sonja; Kurka, Peter; Bernkop-Schnürch, Andreas

2006-03-01

Intravenous application of pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified as a promising strategy for the treatment of type 2 diabetes. To generate a more applicable formulation, it was the aim of this study to develop a sustained buccal delivery system for this promising therapeutic peptide. 2-Iminothiolane was covalently bound to chitosan to improve the mucoadhesive and permeation-enhancing properties of chitosan used as drug carrier matrix. The resulting chitosan-4-thiobutylamidine conjugate was homogenized with the enzyme inhibitor and permeation mediator glutathione (gamma-Glu-Cys-Gly), Brij 35, and PACAP (formulation A). The mixture was lyophilized and compressed into flat-faced discs (18 mm in diameter). One formulation was additionally coated on one side with palm wax (formulation B). Tablets consisting of unmodified chitosan and PACAP (formulation C) or of unmodified chitosan, Brij 35, and PACAP (formulation D) served as controls. Bioavailability studies were performed in pigs by buccal administration of these test formulations. Blood samples were analyzed via an ELISA method. Formulations A and B led to an absolute bioavailability of 1%, whereas PACAP did not reach the systemic circulation when administered via formulations C and D. Moreover, in the case of formulations A and B, a continuously raised plasma level of the peptide drug being in the therapeutic range could be maintained over the whole period of application (6 h). Formulations A and B were removed by moderate force from the buccal mucosa after 6 h, whereas formulations C and D detached from the mucosa 4 h after application. The study reveals this novel mucoadhesive delivery system to be a promising approach for buccal delivery of PACAP.

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.

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

PubMed Central

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

2016-01-01

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

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

Cationic nanoemulsions as nucleic acids delivery systems.

PubMed

Teixeira, Helder Ferreira; Bruxel, Fernanda; Fraga, Michelle; Schuh, Roselena Silvestri; Zorzi, Giovanni Konat; Matte, Ursula; Fattal, Elias

2017-12-20

Since the first clinical studies, knowledge in the field of gene therapy has advanced significantly, and these advances led to the development and subsequent approval of the first gene medicines. Although viral vectors-based products offer efficient gene expression, problems related to their safety and immune response have limited their clinical use. Thus, design and optimization of nonviral vectors is presented as a promising strategy in this scenario. Nonviral systems are nanotechnology-based products composed of polymers or lipids, which are usually biodegradable and biocompatible. Cationic liposomes are the most studied nonviral carriers and knowledge about these systems has greatly evolved, especially in understanding the role of phospholipids and cationic lipids. However, the search for efficient delivery systems aiming at gene therapy remains a challenge. In this context, cationic nanoemulsions have proved to be an interesting approach, as their ability to protect and efficiently deliver nucleic acids for diverse therapeutic applications has been demonstrated. This review focused on cationic nanoemulsions designed for gene therapy, providing an overview on their composition, physicochemical properties, and their efficacy on biological response in vitro and in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Logie, Jennifer

Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P

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

PubMed Central

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

2012-01-01

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

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.

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

PubMed

Dalvadi, Hitesh; Patel, Nikita; Parmar, Komal

2017-05-01

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

Porous Inorganic Drug Delivery Systems-a Review.

PubMed

Sayed, E; Haj-Ahmad, R; Ruparelia, K; Arshad, M S; Chang, M-W; Ahmad, Z

2017-07-01

Innovative methods and materials have been developed to overcome limitations associated with current drug delivery systems. Significant developments have led to the use of a variety of materials (as excipients) such as inorganic and metallic structures, marking a transition from conventional polymers. Inorganic materials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of drugs (antibiotics, anticancer and anti-inflammatories), providing several advantages in formulation and engineering (encapsulation of drug in amorphous form, controlled delivery and improved targeting). This review focuses on key selected developments in porous drug delivery systems. The review provides a short broad overview of porous polymeric materials for drug delivery before focusing on porous inorganic materials (e.g. Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM)) and their utilisation in drug dosage form development. Methods for their preparation and drug loading thereafter are detailed. Several examples of porous inorganic materials, drugs used and outcomes are discussed providing the reader with an understanding of advances in the field and realistic opportunities.

Efficiency performance of China's health care delivery system.

PubMed

Zhang, Luyu; Cheng, Gang; Song, Suhang; Yuan, Beibei; Zhu, Weiming; He, Li; Ma, Xiaochen; Meng, Qingyue

2017-07-01

Improving efficiency performance of the health care delivery system has been on the agenda for the health system reform that China initiated in 2009. This study examines the changes in efficiency performance and determinants of efficiency after the reform to provide evidence to assess the progress of the reform from the perspective of efficiency. Descriptive analysis, Data Envelopment Analysis, the Malmquist Index, and multilevel regressions are used with data from multiple sources, including the World Bank, the China Health Statistical Yearbook, and routine reports. The results indicate that over the last decade, health outcomes compared with health investment were relatively higher in China than in most other countries worldwide, and the trend was stable. The overall efficiency and total factor productivity increased after the reform, indicating that the reform was likely to have had a positive impact on the efficiency performance of the health care delivery system. However, the health care delivery structure showed low system efficiency, mainly attributed to the weakened primary health care system. Strengthening the primary health care system is central to enhancing the future performance of China's health care delivery system. Copyright © 2017 John Wiley & Sons, Ltd.

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

Current and emerging lipid-based systems for transdermal drug delivery.

PubMed

Singla, Sumeet K; Sachdeva, Vishal

2015-01-01

Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

Recent 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

Leadership training design, delivery, and implementation: A meta-analysis.

PubMed

Lacerenza, Christina N; Reyes, Denise L; Marlow, Shannon L; Joseph, Dana L; Salas, Eduardo

2017-12-01

Recent estimates suggest that although a majority of funds in organizational training budgets tend to be allocated to leadership training (Ho, 2016; O'Leonard, 2014), only a small minority of organizations believe their leadership training programs are highly effective (Schwartz, Bersin, & Pelster, 2014), calling into question the effectiveness of current leadership development initiatives. To help address this issue, this meta-analysis estimates the extent to which leadership training is effective and identifies the conditions under which these programs are most effective. In doing so, we estimate the effectiveness of leadership training across four criteria (reactions, learning, transfer, and results; Kirkpatrick, 1959) using only employee data and we examine 15 moderators of training design and delivery to determine which elements are associated with the most effective leadership training interventions. Data from 335 independent samples suggest that leadership training is substantially more effective than previously thought, leading to improvements in reactions (δ = .63), learning (δ = .73), transfer (δ = .82), and results (δ = .72), the strength of these effects differs based on various design, delivery, and implementation characteristics. Moderator analyses support the use of needs analysis, feedback, multiple delivery methods (especially practice), spaced training sessions, a location that is on-site, and face-to-face delivery that is not self-administered. Results also suggest that the content of training, attendance policy, and duration influence the effectiveness of the training program. Practical implications for training development and theoretical implications for leadership and training literatures are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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.

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.

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.

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.

Design and characterization of an ultrasonic lamb-wave power delivery system.

PubMed

Kural, Aleksander; Pullin, Rhys; Holford, Karen; Lees, Jonathan; Naylon, Jack; Paget, Christophe; Featherston, Carol

2013-06-01

In this paper, a novel design for an ultrasonic power transmission system designed for use in aircraft structural monitoring systems is described. The prototype system uses ultrasonic Lamb waves to carry energy along plates, such as those used in aircraft structures, and commercially available piezoelectric patch transducers as the transmitter and receiver. This sets it apart from other acoustic power transmission systems reported to date. The optimum configuration transmitted 12.7 mW of power across a distance of 54 cm in a 1.5-mm-thick aluminum plate, while being driven by a 20-Vpp, 35-kHz sinusoidal electric signal. This is in the same order of magnitude as the power required by the wireless sensors nodes of a structural health monitoring system currently being developed by Cardiff University and its partners. Thus, the power transmission system can be considered a viable component of the power source combination considered for the sensor nodes, which will also include vibration and thermal energy harvesting. The paper describes the design and optimization of the transmission and reception circuits with the use of inductive compensation. The use of laser vibrometry to characterize the transducers and to understand the signal propagation between them is also reported.

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.

New Delivery Systems for the 21st Century.

ERIC Educational Resources Information Center

Van Patten, James J.

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

Strategies for drug delivery to the central nervous system by systemic route.

PubMed

Kasinathan, Narayanan; Jagani, Hitesh V; Alex, Angel Treasa; Volety, Subrahmanyam M; Rao, J Venkata

2015-05-01

Delivery of a drug into the central nervous system (CNS) is considered difficult. Most of the drugs discovered over the past decade are biological, which are high in molecular weight and polar in nature. The delivery of such drugs across the blood-brain barrier presents problems. This review discusses some of the options available to reach the CNS by systemic route. The focus is mainly on the recent developments in systemic delivery of a drug to the CNS. Databases such as Scopus, Google scholar, Science Direct, SciFinder and online journals were referred for preparing this article including 89 references. There are at least nine strategies that could be adopted to achieve the required drug concentration in the CNS. The recent developments in drug delivery are very promising to deliver biologicals into the CNS.

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.

The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery.

PubMed

Cheng, Xinwei; Lee, Robert J

2016-04-01

Lipid nanoparticles (LNPs) have shown promise as delivery vehicles for therapeutic oligonucleotides, including antisense oligos (ONs), siRNA, and microRNA mimics and inhibitors. In addition to a cationic lipid, LNPs are typically composed of helper lipids that contribute to their stability and delivery efficiency. Helper lipids with cone-shape geometry favoring the formation hexagonal II phase, such as dioleoylphosphatidylethanolamine (DOPE), can promote endosomal release of ONs. Meanwhile, cylindrical-shaped lipid phosphatidylcholine can provide greater bilayer stability, which is important for in vivo application of LNPs. Cholesterol is often included as a helper that improves intracellular delivery as well as LNP stability in vivo. Inclusion of a PEGylating lipid can enhance LNP colloidal stability in vitro and circulation time in vivo but may reduce uptake and inhibit endosomal release at the cellular level. This problem can be addressed by choosing reversible PEGylation in which the PEG moiety is gradually released in blood circulation. pH-sensitive anionic helper lipids, such as fatty acids and cholesteryl hemisuccinate (CHEMS), can trigger low-pH-induced changes in LNP surface charge and destabilization that can facilitate endosomal release of ONs. Generally speaking, there is no correlation between LNP activity in vitro and in vivo because of differences in factors limiting the efficiency of delivery. Designing LNPs requires the striking of a proper balance between the need for particle stability, long systemic circulation time, and the need for LNP destabilization inside the target cell to release the oligonucleotide cargo, which requires the proper selection of both the cationic and helper lipids. Customized design and empirical optimization is needed for specific applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomimetics in drug delivery systems: A critical review.

PubMed

Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

2017-05-10

Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of Embedded System Component Utilized in Delivery Integrated Design Project Course

NASA Astrophysics Data System (ADS)

Junid, Syed Abdul Mutalib Al; Hussaini, Yusnira; Nazmie Osman, Fairul; Razak, Abdul Hadi Abdul; Idros, Mohd Faizul Md; Karimi Halim, Abdul

2018-03-01

This paper reports the evaluation of the embedded system component utilized in delivering the integrated electronic engineering design project course. The evaluation is conducted based on the report project submitted as to fulfil the assessment criteria for the integrated electronic engineering design project course named; engineering system design. Six projects were assessed in this evaluation. The evaluation covers the type of controller, programming language and the number of embedded component utilization as well. From the evaluation, the C-programming based language is the best solution preferred by the students which provide them flexibility in the programming. Moreover, the Analog to Digital converter is intensively used in the projects which include sensors in their proposed design. As a conclusion, in delivering the integrated design project course, the knowledge over the embedded system solution is very important since the high density of the knowledge acquired in accomplishing the project assigned.

Novel drug delivery system: an immense hope for diabetics.

PubMed

Rai, Vineet Kumar; Mishra, Nidhi; Agrawal, Ashish Kumar; Jain, Sanyog; Yadav, Narayan Prasad

2016-09-01

Existing medication systems for the treatment of diabetes mellitus (DM) are inconvenient and troublesome for effective and safe delivery of drugs to the specific site. Therefore, investigations are desired to deliver antidiabetics using novel delivery approaches followed by their commercialization. The present review aims to provide a compilation on the latest development in the field of novel drug delivery systems (NDDSs) for antidiabetics with special emphasis on particulate, vesicular and miscellaneous systems. Review of literature (restricted to English language only) was done using electronic databases like Pubmed® and Scirus, i.e. published during 2005-2013. The CIMS/MIMS India Medical Drug Information eBook was used regarding available marketed formulation of antidiabetic drugs. Keywords used were "nanoparticle", "microparticle", "liposomes", "niosomes", "transdermal systems", "insulin", "antidiabetic drugs" and "novel drug delivery systems". Single inclusion was made for one article. If in vivo study was not done then article was seldom included in the manuscript. The curiosity to develop NDDSs of antidiabetic drugs with special attention to the nanoparticulate system followed by microparticulate and lipid-based system is found to emerge gradually to overcome the problems associated with the conventional dosage forms and to win the confidence of end users towards the higher acceptability. In the current scientific panorama when the area of novel drug delivery system has been recognized for its palpable benefits, unique potential of providing physical stability, sustained and site-specific drug delivery for a scheduled period of time can open new vistas for precise, safe and quality treatment of DM.

Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

PubMed

Maity, Amit Ranjan; Stepensky, David

2016-01-04

Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

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.

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.

Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

PubMed Central

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

2012-01-01

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

Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis--A Review.

PubMed

da Silva, Patricia Bento; de Freitas, Eduardo Sinésio; Bernegossi, Jessica; Gonçalez, Maíra Lima; Sato, Mariana Rillo; Leite, Clarice Queico Fujimura; Pavan, Fernando Rogério; Chorilli, Marlus

2016-02-01

Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t₁/₂ (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB.

[Smart drug delivery systems based on nanoscale ZnO].

PubMed

Huang, Xiao; Chen, Chun; Yi, Caixia; Zheng, Xi

2018-04-01

In view of the excellent biocompatibility as well as the low cost, nanoscale ZnO shows great potential for drug delivery application. Moreover, The charming character enable nanoscale ZnO some excellent features (e.g. dissolution in acid, ultrasonic permeability, microwave absorbing, hydrophobic/hydrophilic transition). All of that make nanoscale ZnO reasonable choices for smart drug delivery. In the recent decade, more and more studies have focused on controlling the drug release behavior via smart drug delivery systems based on nanoscale ZnO responsive to some certain stimuli. Herein, we review the recent exciting progress on the pH-responsive, ultrasound-responsive, microwave-responsive and UV-responsive nanoscale ZnO-based drug delivery systems. A brief introduction of the drug controlled release behavior and its effect of the drug delivery systems is presented. The biocompatibility of nanoscale ZnO is also discussed. Moreover, its development prospect is looked forward.

DNA Nanotechnology-Enabled Drug Delivery Systems.

PubMed

Hu, Qinqin; Li, Hua; Wang, Lihua; Gu, Hongzhou; Fan, Chunhai

2018-02-21

Over the past decade, we have seen rapid advances in applying nanotechnology in biomedical areas including bioimaging, biodetection, and drug delivery. As an emerging field, DNA nanotechnology offers simple yet powerful design techniques for self-assembly of nanostructures with unique advantages and high potential in enhancing drug targeting and reducing drug toxicity. Various sequence programming and optimization approaches have been developed to design DNA nanostructures with precisely engineered, controllable size, shape, surface chemistry, and function. Potent anticancer drug molecules, including Doxorubicin and CpG oligonucleotides, have been successfully loaded on DNA nanostructures to increase their cell uptake efficiency. These advances have implicated the bright future of DNA nanotechnology-enabled nanomedicine. In this review, we begin with the origin of DNA nanotechnology, followed by summarizing state-of-the-art strategies for the construction of DNA nanostructures and drug payloads delivered by DNA nanovehicles. Further, we discuss the cellular fates of DNA nanostructures as well as challenges and opportunities for DNA nanostructure-based drug delivery.

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.

Nanogel Carrier Design for Targeted Drug Delivery

PubMed Central

Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

2014-01-01

Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

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

PubMed

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

2014-01-01

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

Development of a Production Ready Automated Wire Delivery System

NASA Technical Reports Server (NTRS)

1997-01-01

The current development effort is a Phase 3 research study entitled "A Production Ready Automated Wire Delivery System", contract number NAS8-39933, awarded to Nichols Research Corporation (NRC). The goals of this research study were to production harden the existing Automated Wire Delivery (AWDS) motion and sensor hardware and test the modified AWDS in a range of welding applications. In addition, the prototype AWDS controller would be moved to the VME bus platform by designing, fabricating and testing a single board VME bus AWDS controller. This effort was to provide an AWDS that could transition from the laboratory environment to production operations. The project was performed in two development steps. Step 1 modified and tested an improved MWG. Step 2 developed and tested the AWDS single board VME bus controller. Step 3 installed the Wire Pilot in a Weld Controller with the imbedded VME bus controller.

Ocular delivery systems for topical application of anti-infective agents.

PubMed

Duxfield, Linda; Sultana, Rubab; Wang, Ruokai; Englebretsen, Vanessa; Deo, Samantha; Rupenthal, Ilva D; Al-Kassas, Raida

2016-01-01

For the treatment of anterior eye segment infections using anti-infective agents, topical ocular application is the most convenient route of administration. However, topical delivery of anti-infective agents is associated with a number of problems and challenges owing to the unique structure of the eye and the physicochemical properties of these compounds. Topical ocular drug delivery systems can be classified into two forms: conventional and non-conventional. The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation resulting in low ocular bioavailability. Recently, attention has been focused on improving topical ocular delivery of anti-infective agents using advanced drug delivery systems. This review will focus on the challenges of efficient topical ocular delivery of anti-infective agents and will discuss the various types of delivery systems used to improve the treatment anterior segment infections.

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape.

PubMed

Zylberberg, Claudia; Matosevic, Sandro

2016-11-01

Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.

Chitosan Microspheres in Novel Drug Delivery Systems

PubMed Central

Mitra, Analava; Dey, Baishakhi

2011-01-01

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

Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D

PubMed Central

Ke, Zhongcheng; Hou, Xuefeng; Jia, Xiao-bin

2016-01-01

Background The main purpose of this research was to design a self-nanoemulsifying drug delivery system (SNEDDS) for improving the bioavailability of cyclovirobuxine D as a poorly water-soluble drug. Materials and methods Solubility trials, emulsifying studies, and pseudo-ternary phase diagrams were used to screen the SNEDDS formulations. The optimized drug-loaded SNEDDS was prepared at a mass ratio of 3:24:38:38 for cyclovirobuxine D, oleic acid, Solutol SH15, and propylene glycol, respectively. The optimized formulation was characterized in terms of physicochemical and pharmacokinetic parameters compared with marketed cyclovirobuxine D tablets. Results The optimized cyclovirobuxine-D-loaded SNEDDS was spontaneously dispersed to form a nanoemulsion with a globule size of 64.80±3.58 nm, which exhibited significant improvement of drug solubility, rapid absorption rate, and enhanced area under the curve, together with increased permeation and decreased efflux. Fortunately, there was a nonsignificant cytotoxic effect toward Caco-2 cells. The relative bioavailability of SNEDDS was 200.22% in comparison with market tablets, in rabbits. Conclusion SNEDDS could be a potential candidate for an oral dosage form of cyclovirobuxine D with improved bioavailability. PMID:27418807

Renewable energy delivery systems and methods

DOEpatents

Walker, Howard Andrew

2013-12-10

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

Lactic acid bacteria as oral delivery systems for biomolecules.

PubMed

Berlec, A; Ravnikar, M; Strukelj, B

2012-11-01

Lactic acid bacteria (LAB) have become increasingly studied over the last two decades as potential delivery systems for various biological molecules to the gastrointestinal tract. This article presents an overview of characteristics of LAB as delivery systems and of the applications which have already been developed. The majority of LAB strains are able to survive the intestinal passage and some are also able to persist and colonize the intestine. Several strains were in fact described as members of the human commensal flora. They can interact with their host and are able to deliver large molecular weight biomolecules across the epithelium via M-cells or dendritic cells. The most widely applied LAB species has been Lactococcus lactis; however species from genus Lactobacillus are gaining popularity and the first examples from genus Bifidobacterium are starting to emerge. Bacteria are mostly applied live and enable continuous delivery of the biomolecules. However, killed bacteria (e.g. gram-positive enhancer matrix), with bound biomolecules or as adjuvants, are also being developed. The techniques for genetic modification of LAB are well known. This review focuses on the delivery of recombinant proteins and DNA, which can cause either local or systemic effects. We divide recombinant proteins into antigens and therapeutic proteins. Delivery of antigens for the purpose of vaccination represents the most abundant application with numerous successful demonstrations of the efficacy on the animal model. Therapeutic proteins have mostly been developed for the treatment of the inflammatory bowel disease, by the delivery of anti-inflammatory cytokines, or downregulation of proinflammatory cytokines. Delivery of allergens for the modulation of allergic disorders represents the second most popular application of therapeutic proteins. The delivery of DNA by LAB was demonstrated and offers exciting opportunities, especially as a vaccine. New discoveries may eventually lead to the

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.

Goals for Postsecondary Instructional Delivery Systems.

ERIC Educational Resources Information Center

Knapp, Stuart E.; Valentine, Carol A.

Extrapolating from the trends in postsecondary instructional delivery systems identified by Brown, Lewis and Harcleroad, this report attempts to identify how these trends might be implemented in Oregon. Separating the systems into technology-centered and people-centered, the report proposes future applications of dial access systems, self learning…

Colloidal drug delivery systems: current status and future directions.

PubMed

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

2015-01-01

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

Nanoscale Delivery Systems: Actual and Potential Applications in the Natural Products Industry.

PubMed

Simona, Antal Diana; Florina, Ardelean; Rodica, Chis Aimee; Evelyne, Ollivier; Maria-Corina, Serban

2017-01-01

Compounds and extracts derived from natural sources continue to stand in the spotlight of drug design owing to their versatile interaction with enzymes, receptors and metabolic pathways. Nanomedicine offers an operative tool for the efficient delivery of natural products, in terms of increased bioavailability, targeting, and controlled release while protecting active constituents against physico-chemical alterations. The interest of the scientific community in the field of nanosized delivery of natural compounds is demonstrated by the exponential growth of the publications in this field. Beyond the presentation of successful examples of nanoscale delivery systems containing natural products, the scope of this review is to point out the yet underexplored capacities of this field with relevance for the pharmaceutical and nutraceutical market. Departing from a short presentation of plant-derived natural products and strategies to obtain nanoformulations, the current work discusses nanoparticulate drug delivery systems targeting diseases of various organs and systems: skin, central nervous system, skeletal tissue, cardiovascular apparatus, and diabetes. While notable progress has been achieved in the preparation of nanomedicines containing selected dietary polyphenols, works dealing with crude extracts or standardized fractions are much less frequent. In fact, most of the plants with solidly documented therapeutic properties and registered in pharmacopoeias still wait to benefit from advances in the field of nanotechnology. At least for some of them, adequate nanoformulation shall contribute to their removal from the group of dietary supplements and pharmaceutical preparations with suboptimal bioavailability and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Handheld Delivery System for Modified Boron-Type Fire Extinguishment Agent

DTIC Science & Technology

1993-11-01

was to develop and test a handheld portable delivery system for use with the modified boron-type fire extinguishing agent for metal fires . B...BACKGROUND A need exists for an extinguishing agent and accompanying delivery system that are effective against complex geometry metal fires . A modified...agent and its delivery system have proven effective against complex geometry metal fires containing up to 200 pounds of magnesium metal. Further

Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

PubMed Central

Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

2016-01-01

Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

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.

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.

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.

Formulation design facilitates magnetic nanoparticle delivery to diseased cells and tissues

PubMed Central

Singh, Dhirender; McMillan, JoEllyn M; Liu, Xin-Ming; Vishwasrao, Hemant M; Kabanov, Alexander V; Sokolsky-Papkov, Marina; Gendelman, Howard E

2015-01-01

Magnetic nanoparticles (MNPs) accumulate at disease sites with the aid of magnetic fields; biodegradable MNPs can be designed to facilitate drug delivery, influence disease diagnostics, facilitate tissue regeneration and permit protein purification. Because of their limited toxicity, MNPs are widely used in theranostics, simultaneously facilitating diagnostics and therapeutics. To realize therapeutic end points, iron oxide nanoparticle cores (5–30 nm) are encapsulated in a biocompatible polymer shell with drug cargos. Although limited, the toxic potential of MNPs parallels magnetite composition, along with shape, size and surface chemistry. Clearance is hastened by the reticuloendothelial system. To surmount translational barriers, the crystal structure, particle surface and magnetic properties of MNPs need to be optimized. With this in mind, we provide a comprehensive evaluation of advancements in MNP synthesis, functionalization and design, with an eye towards bench-to-bedside translation. PMID:24646020

Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs.

PubMed

Araújo, Francisca; Shrestha, Neha; Shahbazi, Mohammad-Ali; Liu, Dongfei; Herranz-Blanco, Bárbara; Mäkilä, Ermei M; Salonen, Jarno J; Hirvonen, Jouni T; Granja, Pedro L; Sarmento, Bruno; Santos, Hélder A

2015-08-25

Multifunctional tailorable composite systems, specifically designed for oral dual-delivery of a peptide (glucagon-like peptide-1) and an enzymatic inhibitor (dipeptidyl peptidase 4 (DPP4)), were assembled through the microfluidics technique. Both drugs were coloaded into these systems for a synergistic therapeutic effect. The systems were composed of chitosan and cell-penetrating peptide modified poly(lactide-co-glycolide) and porous silicon nanoparticles as nanomatrices, further encapsulated in an enteric hydroxypropylmethylcellulose acetylsuccinate polymer. The developed multifunctional systems were pH-sensitive, inherited by the enteric polymer, enabling the release of the nanoparticles only in the simulated intestinal conditions. Moreover, the encapsulation into this polymer prevented the degradation of the nanoparticles' modifications. These nanoparticles showed strong and higher interactions with the intestinal cells in comparison with the nonmodified ones. The presence of DPP4 inhibitor enhanced the peptide permeability across intestinal cell monolayers. Overall, this is a promising platform for simultaneously delivering two drugs from a single formulation. Through this approach peptides are expected to increase their bioavailability and efficiency in vivo both by their specific release at the intestinal level and also by the reduced enzymatic activity. The use of this platform, specifically in combination of the two antidiabetic drugs, has clinical potential for the therapy of type 2 diabetes mellitus.

Calcium carbonate nanoparticles as cancer drug delivery system.

PubMed

Maleki Dizaj, Solmaz; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad Hossein; Adibkia, Khosro; Lotfipour, Farzaneh

2015-01-01

Calcium carbonate (CaCO3) has broad biomedical utilizations owing to its availability, low cost, safety, biocompatibility, pH-sensitivity and slow biodegradability. Recently, there has been widespread interest in their application as drug delivery systems for different groups of drugs. Among them, CaCO3 nanoparticles have exhibited promising potential as drug carriers targeting cancer tissues and cells. The pH-dependent properties, alongside the potential to be functionalized with targeting agents give them the unique property that can be used in targeted delivery systems for anticancer drugs. Also, due to the slow degradation of CaCO3 matrices, these nanoparticles can be used as sustained release systems to retain drugs in cancer tissues for longer times after administration. Development of drug delivery carriers using CaCO3 nanoparticles has been reviewed. The current state of CaCO3 nanoparticles as cancer drug delivery systems with focus on their special properties like pH-sensitivity and biodegradability has also been evaluated. According to our review, CaCO3 nanoparticles, owing to their special characteristics, will have a potential role in safe and efficient cancer treatment in future.

Crowd-sourcing delivery system innovation: A public-private solution.

PubMed

Agrawal, Shantanu; Chen, Christopher; Tanio, Craig P

2015-03-01

We propose the establishment of a public-private approach which creates and maintains a "delivery systems innovations knowledge management system" to define, describe, and assess novel delivery approaches. The public sector could provide the foundational technology, resources and convening power for this innovations database. The private sector would contribute practical innovations that could guide annual strategic planning and implementation. A crowd-sourced effort would jump start delivery system reform. We believe that providing a comprehensive knowledge resource will not stifle competition or private sector opportunities but rather augment and speed the application of effective innovation. Copyright © 2014 Elsevier Inc. All rights reserved.

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…

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.

Designing synthetic RNA for delivery by nanoparticles

NASA Astrophysics Data System (ADS)

Jedrzejczyk, Dominika; Gendaszewska-Darmach, Edyta; Pawlowska, Roza; Chworos, Arkadiusz

2017-03-01

The rapid development of synthetic biology and nanobiotechnology has led to the construction of various synthetic RNA nanoparticles of different functionalities and potential applications. As they occur naturally, nucleic acids are an attractive construction material for biocompatible nanoscaffold and nanomachine design. In this review, we provide an overview of the types of RNA and nucleic acid’s nanoparticle design, with the focus on relevant nanostructures utilized for gene-expression regulation in cellular models. Structural analysis and modeling is addressed along with the tools available for RNA structural prediction. The functionalization of RNA-based nanoparticles leading to prospective applications of such constructs in potential therapies is shown. The route from the nanoparticle design and modeling through synthesis and functionalization to cellular application is also described. For a better understanding of the fate of targeted RNA after delivery, an overview of RNA processing inside the cell is also provided.

Fe₃O₄ Nanoparticles in Targeted Drug/Gene Delivery Systems.

PubMed

Shen, Lazhen; Li, Bei; Qiao, Yongsheng

2018-02-23

Fe₃O₄ nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe₃O₄ NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe₃O₄ NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe₃O₄ NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe₃O₄ NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe₃O₄ NPs targeting drug/gene delivery systems.

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.

A Novel Nonviral Gene Delivery System: Multifunctional Envelope-Type Nano Device

NASA Astrophysics Data System (ADS)

Hatakeyama, Hiroto; Akita, Hidetaka; Kogure, Kentaro; Harashima, Hideyoshi

In this review we introduce a new concept for developing a nonviral gene delivery system which we call "Programmed Packaging." Based on this concept, we succeeded in developing a multifunctional envelope-type nano device (MEND), which exerts high transfection activities equivalent to those of an adenovirus in a dividing cell. The use of MEND has been extended to in vivo applications. PEG/peptide/DOPE ternary conjugate (PPD)-MEND, a new in vivo gene delivery system for the targeting of tumor cells that dissociates surface-modified PEG in tumor tissue by matrix metalloproteinase (MMP) and exerts significant transfection activities, was developed. In parallel with the development of MEND, a quantitative gene delivery system, Confocal Image-assisted 3-dimensionally integrated quantification (CIDIQ), also was developed. This method identified the rate-limiting step of the nonviral gene delivery system by comparing it with adenoviral-mediated gene delivery. The results of this analysis provide a new direction for the development of rational nonviral gene delivery systems.

Guidelines for Psychological Practice in Health Care Delivery Systems

ERIC Educational Resources Information Center

American Psychologist, 2013

2013-01-01

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

Viability, Advantages and Design Methodologies of M-Learning Delivery

ERIC Educational Resources Information Center

Zabel, Todd W.

2010-01-01

The purpose of this study was to examine the viability and principle design methodologies of Mobile Learning models in developing regions. Demographic and market studies were utilized to determine the viability of M-Learning delivery as well as best uses for such technologies and methods given socioeconomic and political conditions within the…

Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses.

PubMed

Ribeiro, Andreza Maria; Figueiras, Ana; Veiga, Francisco

2015-01-01

Conventional ophthalmic systems present very low corneal systemic bioavailability due to the nasolacrimal drainage and the difficulty to deliver the drug in the posterior segment of ocular tissue. For these reasons, recent advances have focused on the development of new ophthalmic drug delivery systems. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings in soft contact lenses (SCL) and the applications of novel pharmaceutical systems for ocular drug delivery. Among the new therapeutic approaches in ophthalmology, SCL are novel continuous-delivery systems, providing high and sustained levels of drugs to the cornea. The tendency of research in ophthalmic drug delivery systems development are directed towards a combination of several technologies (bio-inspired and molecular imprinting techniques) and materials (cyclodextrins, surfactants, specific monomers). There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but also at the same time slow down the clearance of the drug. Different materials can be applied during the development of contact lenses and can be combined with natural inspired strategies of drug immobilization and release, providing successful tools for ocular drug delivery systems.

Measuring primary care practice performance within an integrated delivery system: a case study.

PubMed

Stewart, Louis J; Greisler, David

2002-01-01

This article examines the use of an integrated performance measurement system to plan and control primary care service delivery within an integrated delivery system. We review a growing body of literature that focuses on the development and implementation of management reporting systems among healthcare providers. Our study extends the existing literature by examining the use of performance information generated by an integrated performance measurement system within a healthcare organization. We conduct our examination through a case study of the WMG Primary Care Medicine Group, the primary care medical group practice of WellSpan Health System. WellSpan Health System is an integrated delivery system that serves south central Pennsylvania and northern Maryland. Our study examines the linkage between WellSpan Health's strategic objectives and its primary care medicine group's integrated performance measurement system. The conceptual design of this integrated performance measurement system combines financial metrics with practice management and clinical operating metrics to provide a more complete picture of medical group performance. Our findings demonstrate that WellSpan Health was able to achieve superior financial results despite a weak linkage between its integrated performance measurement system and its strategic objectives. WellSpan Health achieved this objective for its primary care medicine group by linking clinical performance information to physician compensation and reporting practice management performance through the use of statistical process charts. They found that the combined mechanisms of integrated performance measurement and statistical process control charts improved organizational learning and communications between organizational stakeholders.

Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors

NASA Astrophysics Data System (ADS)

Zhu, Yu

Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo

Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

PubMed Central

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

2014-01-01

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

Biodegradable polymers for targeted delivery of anti-cancer drugs.

PubMed

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

2016-06-01

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

Behavioral Design Teams: The Next Frontier in Clinical Delivery Innovation?

PubMed

Robertson, Ted; Darling, Matthew; Leifer, Jennifer; Footer, Owen; Gordski, Dani

2017-11-01

A deep understanding of human behavior is critical to designing effective health care delivery models, tools, and processes. Currently, however, few mechanisms exist to systematically apply insights about human behavior to improve health outcomes. Behavioral design teams (BDTs) are a successful model for applying behavioral insights within an organization. Already operational within government, this model can be adapted to function in a health care setting. To explore how BDTs could be applied to clinical care delivery and review models for integrating these teams within health care organizations. Interviews with experts in clinical delivery innovation and applied behavioral science, as well as leaders of existing government BDTs. BDTs are most effective when they enjoy top-level executive support, are co-led by a domain expert and behavioral scientist, collaborate closely with key staff and departments, have access to data and IT support, and operate a portfolio of projects. BDTs could be embedded in health care organizations in multiple ways, including in or just below the CEO’s office, within a quality improvement unit, or within an internal innovation center. When running a portfolio, BDTs achieve a greater number and diversity of insights at lower costs. They also become a platform for strategic learning and scaling.

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.

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.

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.

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.

Magnetic Responsive Hydrogel Material Delivery System II

DTIC Science & Technology

2010-08-29

phase. MNPs have found very useful applications in bioseparation, drug delivery system, hyperthermia for cancer therapy, and magnetic resonance...and the poly(N-isoproplyacrylamide) (poly(NIPAAm) shell in aqueous medium. Magnetic nanoparticles (MNPs) were coated with first oleic acid (OA) and...potentially important in target delivery of therapeutic agent in vivo, hyperthermic treatment of tumors, magnetic resonance imaging (MRI) as contrasting

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

Carrier-Based Drug Delivery System for Treatment of Acne

PubMed Central

Vyas, Amber; Kumar Sonker, Avinesh

2014-01-01

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

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.

Nanovehicular Intracellular Delivery Systems

PubMed Central

PROKOP, ALES; DAVIDSON, JEFFREY M.

2013-01-01

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

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.

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

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

J Torin Huzil; S Sivaloganathan; M Kohandel

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

Opportunities and Challenges for Niosomes as Drug Delivery Systems.

PubMed

Thakkar, Miloni; Brijesh, S

2016-01-01

With the increase in drug resistance observed in most infectious diseases as well as some forms of cancer, and with the chances of development of new drug molecules to address this issue looking bleak, one of the most plausible ways to disease treatment is combination therapy. Combination therapy would ensure delay in drug resistance, if utilized rationally. However, the biggest difficulty in employing combination therapy are adverse effects due to potential drug-drug interactions and patient compliance due to multiple routes of administration or multiple dosing that may be required. To overcome these issues, researchers have utilized nanoparticle-based systems that can hold multiple drugs in a single carrier. There are several nanocarrier systems available for such purposes. However, the focus of this review will be non-ionic surfactant-based systems (niosomes) for delivery of multiple therapeutic agents. Niosomes are artificially prepared drug delivery carriers. They are structurally similar to liposomes albeit more stable than them. Literature pertaining to combination drug delivery and various drug delivery systems was reviewed. It was conceptualized that many of the methods used to prepare various types of carriers for combination delivery of drugs may be used for niosomal systems as well. We envisage that niosomes may effectively be utilized to package older drugs in newer ways. The review will thus focus on techniques that may be used for the formulation of niosomes, ways to encapsulate multiple-drug moieties, and challenges associated in preparing and optimizing such systems.

Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

PubMed Central

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

2014-01-01

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

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.

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

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

PubMed Central

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

2015-01-01

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.

PubMed

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

2015-10-09

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

Collaboration in the design and delivery of a mental health Recovery College course: experiences of students and tutors.

PubMed

Cameron, Josh; Hart, Angie; Brooker, Saff; Neale, Paul; Reardon, Mair

2018-05-15

Recovery Colleges address mental health challenges using an educative approach underpinned by a collaborative recovery orientated philosophy. Research has been limited with no studies identified reporting research on the design and delivery of a specific course. To understand how Recovery College students and tutors experience the design and delivery of a mental health Recovery College course, specifically the "'Building Resilience" course. Thematic analysis of qualitative data related to the experience and process of collaboration in recovery college course design and delivery. Data included 13 qualitative individual interviews with course students and tutors and "naturally occurring" data generated through course preparation and delivery. Findings drew attention to the centrality of: prior experience and design related to students, tutors and the course structure; co-delivery related to tutors and co-learner impacts; and to the course methods and environment. Commitment to collaboration in design and delivery of Recovery College courses can mobilise the diverse experiences and expertise of tutors and students. The environment and methods of learning have a significant impact and should be considered alongside content. Boundaries between people and areas of knowledge and experience that arise can be viewed as sources of creativity that can enrich courses.

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.

Intrathecal Drug Delivery Systems for Noncancer Pain: A Health Technology Assessment.

PubMed

2016-01-01

Intrathecal drug delivery systems can be used to manage refractory or persistent chronic nonmalignant (noncancer) pain. We investigated the benefits, harms, cost-effectiveness, and budget impact of these systems compared with current standards of care for adult patients with chronic pain owing to nonmalignant conditions. We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library, and the National Health Service's Economic Evaluation Database and Tufts Cost-Effectiveness Analysis Registry from January 1994 to April 2014 for evidence of effectiveness, harms, and cost-effectiveness. We used existing systematic reviews that had employed reliable search and screen methods and also searched for studies published after the search date reported in the latest systematic review to identify studies. Two reviewers screened records and assessed study validity. We found comparative evidence of effectiveness and harms in one cohort study at high risk of bias (≥ 3-year follow-up, N = 130). Four economic evaluations of low to very low quality were also included. Compared with oral opioid analgesia alone or a program of analgesia plus rehabilitation, intrathecal drug delivery systems significantly reduced pain (27% additional improvement) and morphine consumption. Despite these reductions, intrathecal drug delivery systems were not superior in patient-reported well-being or quality of life. There is no evidence of superiority of intrathecal drug delivery systems over oral opioids in global pain improvement and global treatment satisfaction. Comparative evidence of harms was not found. Cost-effectiveness evidence is of insufficient quality to assess the appropriateness of funding intrathecal drug delivery systems. Evidence comparing intrathecal drug delivery systems with standard care was of very low quality. Current evidence does not establish (or rule out) superiority or cost-effectiveness of intrathecal drug delivery systems for managing chronic refractory nonmalignant pain

In Situ Lipidization as a New Approach for the Design of a Self Microemulsifying Drug Delivery System (SMEDDS) of Doxorubicin Hydrochloride for Oral Administration.

PubMed

Derajram M Benival, M; Devarajan, Padma V

2015-05-01

The present paper reports in situ lipidization as a novel approach for the design of Dox-self microemulsifying drug delivery system (SMEDDS). Dox-aerosol OT (AOT) ion pair complex (lipidized Dox), exhibited high log P value of 1.74, indicating lipophilic nature. The lipidized Dox revealed good solubility but limited stability in various oils. Rapid complex formation of Dox with AOT dissolved in oils, and the high partitioning of lipidized Dox (-90%) into the oily phase presented in situ lipidization as a strategy to overcome the limited chemical stability of lipidized Dox. SMEDDS was prepared by mixing the lipidizing agent AOT, the surfactant α-Tocopheryl-Polyethyleneglycol-1 000-Succinate (TPGS) and Capmul as the oil. Dox was suspended in the SMEDDS to obtain Dox-SMEDDS. Dox-SMEDDS on aqueous dilution, resulted in a microemulsion with globule size 196 ± 16.56 nm, and revealed slow release of Dox. Oral bioavailability study in rats revealed a 420% enhancement from Dox-SMEDDS compared to Dox solution. Dox-SMEDDS and control group revealed comparable superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels in heart and kidneys suggesting safety of the Dox-SMEDDS. Efficacy study (tumor size reduction) in fibrosarcoma mouse model suggested Dox-SMEDDS as a promising oral delivery system for the treatment of cancer. In situ lipidization of Dox in SMEDDS presents a novel approach for the design of an orally bioavailable and promising formulation of Dox for oral administration.

Chitosan nanoparticle based delivery systems for sustainable agriculture.

PubMed

Kashyap, Prem Lal; Xiang, Xu; Heiden, Patricia

2015-01-01

Development of technologies that improve food productivity without any adverse impact on the ecosystem is the need of hour. In this context, development of controlled delivery systems for slow and sustained release of agrochemicals or genetic materials is crucial. Chitosan has emerged as a valuable carrier for controlled delivery of agrochemicals and genetic materials because of its proven biocompatibility, biodegradability, non-toxicity, and adsorption abilities. The major advantages of encapsulating agrochemicals and genetic material in a chitosan matrix include its ability to function as a protective reservoir for the active ingredients, protecting the ingredients from the surrounding environment while they are in the chitosan domain, and then controlling their release, allowing them to serve as efficient gene delivery systems for plant transformation or controlled release of pesticides. Despite the great progress in the use of chitosan in the area of medical and pharmaceutical sciences, there is still a wide knowledge gap regarding the potential application of chitosan for encapsulation of active ingredients in agriculture. Hence, the present article describes the current status of chitosan nanoparticle-based delivery systems in agriculture, and to highlight challenges that need to be overcome. Copyright © 2015 Elsevier B.V. All rights reserved.

Warehouses information system design and development

NASA Astrophysics Data System (ADS)

Darajatun, R. A.; Sukanta

2017-12-01

Materials/goods handling industry is fundamental for companies to ensure the smooth running of their warehouses. Efficiency and organization within every aspect of the business is essential in order to gain a competitive advantage. The purpose of this research is design and development of Kanban of inventory storage and delivery system. Application aims to facilitate inventory stock checks to be more efficient and effective. Users easily input finished goods from production department, warehouse, customer, and also suppliers. Master data designed as complete as possible to be prepared applications used in a variety of process logistic warehouse variations. The author uses Java programming language to develop the application, which is used for building Java Web applications, while the database used is MySQL. System development methodology that I use is the Waterfall methodology. Waterfall methodology has several stages of the Analysis, System Design, Implementation, Integration, Operation and Maintenance. In the process of collecting data the author uses the method of observation, interviews, and literature.

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…

Delivery system for molten salt oxidation of solid waste

DOEpatents

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

2002-01-01

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

Emulsomes Meet S-layer Proteins: An Emerging Targeted Drug Delivery System

PubMed Central

Ucisik, Mehmet H.; Sleytr, Uwe B.; Schuster, Bernhard

2015-01-01

Here, the use of emulsomes as a drug delivery system is reviewed and compared with other similar lipidic nanoformulations. In particular, we look at surface modification of emulsomes using S-layer proteins, which are self-assembling proteins that cover the surface of many prokaryotic organisms. It has been shown that covering emulsomes with a crystalline S-layer lattice can protect cells from oxidative stress and membrane damage. In the future, the capability to recrystallize S-layer fusion proteins on lipidic nanoformulations may allow the presentation of binding functions or homing protein domains to achieve highly specific targeted delivery of drug-loaded emulsomes. Besides the discussion on several designs and advantages of composite emulsomes, the success of emulsomes for the delivery of drugs to fight against viral and fungal infections, dermal therapy, cancer, and autoimmunity is summarized. Further research might lead to smart, biocompatible emulsomes, which are able to protect and reduce the side effects caused by the drug, but at the same time are equipped with specific targeting molecules to find the desired site of action. PMID:25697368

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.

A self-powered kinesin-microtubule system for smart cargo delivery

NASA Astrophysics Data System (ADS)

Jia, Yi; Dong, Weiguang; Feng, Xiyun; Li, Jieling; Li, Junbai

2014-11-01

A smart self-powered cargo delivery system that is composed of creatine phosphate kinase (CPK) microspheres, kinesins and microtubules is demonstrated. The CPK microsphere not only acts as an ATP generation and buffering system, but also as a carrier for cargo transport, thus realizing the easy loading and self-powered delivery of cargos at the same time.A smart self-powered cargo delivery system that is composed of creatine phosphate kinase (CPK) microspheres, kinesins and microtubules is demonstrated. The CPK microsphere not only acts as an ATP generation and buffering system, but also as a carrier for cargo transport, thus realizing the easy loading and self-powered delivery of cargos at the same time. Electronic supplementary information (ESI) available: Experimental details, Fig. S1-S4, and Mov. S1-S6. See DOI: 10.1039/c4nr04454a

Nebuliser systems for drug delivery in cystic fibrosis.

PubMed

Daniels, Tracey; Mills, Nicola; Whitaker, Paul

2013-04-30

Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing

[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.

Spray-on transdermal drug delivery systems.

PubMed

Ibrahim, Sarah A

2015-02-01

Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

An Overview of Clinical and Commercial Impact of Drug Delivery Systems

PubMed Central

Anselmo, Aaron C.; Mitragotri, Samir

2014-01-01

Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. PMID:24747160

An overview of clinical and commercial impact of drug delivery systems.

PubMed

Anselmo, Aaron C; Mitragotri, Samir

2014-09-28

Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Understanding the organization of public health delivery systems: an empirical typology.

PubMed

Mays, Glen P; Scutchfield, F Douglas; Bhandari, Michelyn W; Smith, Sharla A

2010-03-01

Policy discussions about improving the U.S. health care system increasingly recognize the need to strengthen its capacities for delivering public health services. A better understanding of how public health delivery systems are organized across the United States is critical to improvement. To facilitate the development of such evidence, this article presents an empirical method of classifying and comparing public health delivery systems based on key elements of their organizational structure. This analysis uses data collected through a national longitudinal survey of local public health agencies serving communities with at least 100,000 residents. The survey measured the availability of twenty core public health activities in local communities and the types of organizations contributing to each activity. Cluster analysis differentiated local delivery systems based on the scope of activities delivered, the range of organizations contributing, and the distribution of effort within the system. Public health delivery systems varied widely in organizational structure, but the observed patterns of variation suggested that systems adhere to one of seven distinct configurations. Systems frequently migrated from one configuration to another over time, with an overall trend toward offering a broader scope of services and engaging a wider range of organizations. Public health delivery systems exhibit important structural differences that may influence their operations and outcomes. The typology developed through this analysis can facilitate comparative studies to identify which delivery system configurations perform best in which contexts.

Added health benefits of the levonorgestrel contraceptive intrauterine system and other hormonal contraceptive delivery systems.

PubMed

Fraser, Ian S

2013-03-01

It has been recognized for well over half a century that hormonal preparations designed as contraceptives are also capable of offering health benefits through the treatment and prevention of benign gynecological disease and even some systemic conditions. Increasing attention is now being paid to the extent and detail of such added health benefits, and it is becoming clear that the long-acting, low-dose, hormonal contraceptive delivery systems may offer particular advantages in this regard. Conventional databases were thoroughly searched, especially for publications from 2006 to 2012, which addressed non-contraceptive-related indications for therapy and prevention. A considerable literature now exists to demonstrate the multiple and substantial noncontraceptive health benefits of long-acting progestogen-releasing systems, especially the levonorgestrel-releasing intrauterine system. These benefits mainly relate to disturbances of menstruation and related symptoms, such as heavy menstrual bleeding (due to many causes); iron deficiency; pelvic pain, especially around endometriosis; and endometrial hyperplasia. The long-acting estrogen-progestogen systems may carry similar added health benefits to those of the combined oral contraceptives, but data are still lacking. Added health benefits are now becoming an important part of the contraceptive choice equation, and the long-acting delivery systems are recognized as suitable primary therapies for a range of gynecological disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Porous silicon for drug delivery systems

NASA Astrophysics Data System (ADS)

Abramova, E. N.; Khort, A. M.; Yakovenko, A. G.; Kornilova, D. S.; Slipchenko, E. A.; Prokhorov, D. I.; Shvets, V. I.

2018-01-01

The article deals with main principles of the formation of porous silicon (por-Si) to produce containers for drug delivery systems. Most important por-Si characteristics to produce nanocontainers with required parameters are determined.

Advances in Drug Delivery Systems, from 0 to 3D superstructures.

PubMed

Radulescu, Marius; Popescu, Simona; Ficai, Denisa; Sonmez, Maria; Oprea, Ovidiu; Spoiala, Angela; Ficai, Anton; Andronescu, Ecaterina

2018-02-19

Nanomedicine is currently exploited for manufacturing therapeutic DDS and treatments protocols for various diseases and disorders. To obtain DDS, different types of materials are used, from organic to inorganic, polar to non-polar, micro to nanomaterials from 0D to 3D structured materials, respectively. Many of these materials were extensively studied and reviewed in the literature. The objectives of this review is to make a clear overview on drug delivery systems depending several aspects related to delivery mechanisms, the type of supports, the active agents ant the potential applications in the prevention or treatment of various diseases. Following aspects are extensively debated: synthesis issues, characteristics and potential uses of 0, 1, 2 and 3D drug delivery systems according to their nature and applications. These systems can be can be tailored according to the delivery mechanism (0-3D delivery) as well as by using more active agents, with more therapeutic activity or same activity but with different mechanisms of action. The size and morphology of the drug delivery system is essential, especially when talking about the internalization into the tumor cells while the mobility is especially dependent on the size. The influence of the nature of the supports and their polarity was extensively studied during the last decades, as well as the importance of the porosity and pore size, but only limited papers are devoted to the holistic analysis of the dimensionality of the support and the ways of delivering the active agents. This review is devoted to a holistic insight into the drug delivery systems, from a new, only marginally studied point of view, meaning the dimensionality of the drug delivery systems and the characteristics of the delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

NASA Astrophysics Data System (ADS)

Kaishan, Liu; Huimin, Li

2017-12-01

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

Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

ERIC Educational Resources Information Center

Prausnitz, Mark R.; Bommarius, Andreas S.

2011-01-01

We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

Description and Documentation of the Dental School Dental Delivery System.

ERIC Educational Resources Information Center

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

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

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

PubMed

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

2017-03-01

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

Using CASE Software to Teach Undergraduates Systems Analysis and Design.