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

Pharmacokinetic characteristics of formulated alendronate transdermal delivery systems in rats and humans.

PubMed

Choi, Ahyoung; Gang, Hyesil; Whang, Jiae; Gwak, Hyesun

2010-05-01

The objective of this study was to examine the absorption of alendronate from formulated transdermal delivery systems in rats and humans. When alendronate was applied to rats by transdermal delivery systems (7.2 mg) and oral administration (30 mg/kg), a statistically significant difference was found in the amount remaining to be excreted at time t (Ae(t)) and the amount remaining to be excreted at time 0 (Ae(infinity)) (p < 0.01). The highest Ae(infinity) (1267.7+/-65.2 ng) was found in the formulation containing 6% caprylic acid in propylene glycol (PG), which was 5.4- and 2.0-times higher than the PG only formulation and oral administration, respectively. Compared to oral administration, significantly delayed half-life values were obtained from all the formulated transdermal delivery systems. There was a linear relationship (r(2) = 0.9854) between the drug loading dose and Ae(infinity). The Ae(infinity) values from the transdermal delivery system containing 6% caprylic acid (53.8 mg as alendronate) and an oral product (Fosamax), 70 mg as alendronate) in humans were 127.0 +/- 34.2 microg and 237.2 +/- 56.3 microg, respectively. The dose-adjusted relative Ae(infinity) ratio of the transdermal delivery system to oral product was calculated to be 69.7%. The long half-life of alendronate in the transdermal delivery system (50.6 +/- 6.4 h), compared to that of the oral product (3.5 +/- 1.1 h) could allow less-frequent dosing. In conclusion, this study showed that a transdermal delivery system containing 6% caprylic acid in PG could be a favorable alternative for alendronate administration.

Efficient systemic DNA delivery to the tumor by self-assembled nanoparticle

NASA Astrophysics Data System (ADS)

Tang, Hailin; Xie, Xinhua; Guo, Jiaoli; Wei, Weidong; Wu, Minqing; Liu, Peng; Kong, Yanan; Yang, Lu; Hung, Mien-Chie; Xie, Xiaoming

2014-01-01

There are few delivery agents that could deliver gene with high efficiency and low toxicity, especially for animal experiments. Therefore, creating vectors with good delivery efficiency and safety profile is a meaningful work. We have developed a self-assembled gene delivery system (XM001), which can more efficiently deliver DNA to multiple cell lines and breast tumor, as compared to commercial delivery agents. In addition, systemically administrated XM001-BikDD (BikDD is a mutant form of proapoptotic gene Bik) significantly inhibited the growth of human breast cancer cells and prolonged the life span in implanted nude mice. This study demonstrates that XM001 is an efficient and widespread transfection agent, which could be a promising tumor delivery vector for cancer targeted therapy.

Nano-enabled drug delivery systems for brain cancer and Alzheimer's disease: research patterns and opportunities.

PubMed

Ma, Jing; Porter, Alan L; Aminabhavi, Tejraj M; Zhu, Donghua

2015-10-01

"Tech mining" applies bibliometric and text analytic methods to scientific literature of a target field. In this study, we compare the evolution of nano-enabled drug delivery (NEDD) systems for two different applications - viz., brain cancer (BC) and Alzheimer's disease (AD) - using this approach. In this process, we derive research intelligence from papers indexed in MEDLINE. Review by domain specialists helps understand the macro-level disease problems and pathologies to identify commonalities and differences between BC and AD. Results provide a fresh perspective on the developmental pathways for NEDD approaches that have been used in the treatment of BC and AD. Results also point toward finding future solutions to drug delivery issues that are critical to medical practitioners and pharmaceutical scientists addressing the brain. Drug delivery to brain cells has been very challenging due to the presence of the blood-brain barrier (BBB). Suitable and effective nano-enabled drug delivery (NEDD) system is urgently needed. In this study, the authors utilized "tech-mining" tools to describe and compare various choices of delivery system available for the diagnosis, as well as treatment, of brain cancer and Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Lymphatic delivery of etanercept via nanotopography improves response to collagen-induced arthritis.

PubMed

Aldrich, Melissa B; Velasquez, Fred C; Kwon, Sunkuk; Azhdarinia, Ali; Pinkston, Kenneth; Harvey, Barrett R; Chan, Wenyaw; Rasmussen, John C; Ross, Russell F; Fife, Caroline E; Sevick-Muraca, E M

2017-05-31

Evidence suggests lymphatic function mediates local rheumatoid arthritis (RA) flares. Yet biologics that target the immune system are dosed systemically via the subcutaneous (SC) administration route, thereby inefficiently reaching local lymphatic compartments. Nanotopography has previously been shown to disrupt tight cellular junctions, potentially enhancing local lymphatic delivery and potentially improving overall therapeutic efficacy. We first characterized nanotopography (SOFUSA™) delivery of an anti-TNF drug, etanercept, by comparing pharmacokinetic profiles to those obtained by conventional SC, intravenous (IV), and intradermal (ID) routes of administration, and assessed uptake of radiolabeled etanercept in draining lymph nodes (LNs) in single dosing studies. We then compared etanercept efficacy in a progressive rat model of collagen-induced arthritis (CIA), administered systemically via SC route of administration; via the regional lymphatics through ID delivery; or through a nanotopography (SOFUSA™) device at 10, 12, and 14 days post CIA induction. Measurements of hind limb swelling and near-infrared fluorescence (NIRF) imaging of afferent lymph pumping function and reflux were conducted on days 11, 13, and 18 post CIA induction and compared to untreated CIA animals. Univariate and multivariate analysis of variance were used to compare the group differences for percentage swelling and lymphatic contractile activity. Even though all three modes of administration delivered an equal amount of etanercept, SOFUSA™ delivery resulted in increased lymphatic pumping and significantly reduced swelling as compared to untreated, ID, and SC groups. Pharmacokinetic profiles in serum and LN uptake studies showed that using the nanotopography device resulted in the greatest uptake and retention in draining LNs. Locoregional lymphatic delivery of biologics that target the immune system may have more favorable pharmacodynamics than SC or IV administration. Nanotopography may provide a more efficient method for delivery of anti-TNF drugs to reverse impairment of lymphatic function and reduce swelling associated with RA flares.

A Qualitative Case Study Comparing a Computer-Mediated Delivery System to a Face-to-Face Mediated Delivery System for Teaching Creative Writing Fiction Workshops

ERIC Educational Resources Information Center

Daniels, Mindy A.

2012-01-01

The purpose of this case study was to compare the pedagogical and affective efficiency and efficacy of creative prose fiction writing workshops taught via asynchronous computer-mediated online distance education with creative prose fiction writing workshops taught face-to-face in order to better understand their operational pedagogy and…

Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug.

PubMed

Shim, Gayong; Han, Su-Eun; Yu, Yong-Hee; Lee, Sangbin; Lee, Han Young; Kim, Kwangmeyung; Kwon, Ick Chan; Park, Tae Gwan; Kim, Young Bong; Choi, Yong Seok; Kim, Chan-Wha; Oh, Yu-Kyoung

2011-10-10

Oligolysine-based cationic lipid derivatives were synthesized for delivery of siRNA, and formulated into cationic liposomes. Among various oligolysine-based lipid derivatives differing in lysine residue number and lipid moiety, trilysinoyl oleylamide (TLO)-based liposomes (TLOL) showed the highest delivery efficiency combined with minimal cytotoxicity. Delivery of siRNA using TLOL silenced target genes both in vitro and in vivo. In green fluorescent protein (GFP)-expressing tumor tissue, a significant reduction of fluorescence was observed after intratumoral administration of siGFP using TLOL compared with control siGL2. Intravenous administration of siMcl1 employing pegylated TLOL (pTLOL) reduced the expression of human Mcl1 protein in KB-xenografted tumor tissue. Despite the reduction in target protein Mcl1 expression following such systemic delivery, tumor growth was only slightly reduced compared to a siGL2-treated control group. To potentiate the anticancer activity of siMcl1, the anticancer drug suberoylanilide hydroxamic acid (SAHA) was additionally encapsulated in pTLOL. After intravenous administration of siMcl1 using SAHA-loaded pTLOL (pSTLOL), a significant reduction in tumor growth was observed compared to that seen in animals treated with free SAHA or siGL2 complexed with pSTLOL. The results indicate that pTLOL could be further developed as a systemic delivery system for synergistic anticancer siRNA and a drug. Copyright © 2010 Elsevier B.V. All rights reserved.

Superparamagnetic Iron Oxide Nanoparticle-Based Delivery Systems for Biotherapeutics

PubMed Central

Mok, Hyejung; Zhang, Miqin

2014-01-01

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

Intra-arterial catheter system to repeatedly deliver mesenchymal stem cells in a rat renal failure model.

PubMed

Katsuoka, Yuichi; Ohta, Hiroki; Fujimoto, Eisuke; Izuhara, Luna; Yokote, Shinya; Kurihara, Sho; Yamanaka, Shuichiro; Tajiri, Susumu; Chikaraish, Tatsuya; Okano, Hirotaka J; Yokoo, Takashi

2016-04-01

Mesenchymal stem cell therapy in renal failure is rarely used because of low rates of cell engraftment after systemic delivery. Repeated intra-arterial cell administration may improve results; however, no current delivery method permits repeated intra-arterial infusions in a rat model. In this study, we developed an intra-arterial delivery system for repeated stem cell infusion via the aorta, catheterizing the left femoral artery to the suprarenal aorta under fluoroscopic guidance in rats with adenosine-induced renal failure. First, we compared our intra-arterial catheter system (C group, n = 3) with tail vein injection (V group, n = 3) for engraftment efficacy, using mesenchymal stem cells from luciferase transgenic rats. Rats were infused with the cells and euthanized the following day; we performed cell-tracking experiments using a bioluminescence imaging system to assess the distribution of the infused cells. Second, we assessed the safety of the system over a 30-day period in a second group of six rats receiving infusions every 7 days. Cells infused through our delivery system efficiently engrafted into the kidney, compared with peripheral venous infusion. In five of the six rats in the safety study, the delivery system remained patent for at least 9 days (range, 9-24 days). Complications became evident only after 10 days. Our intra-arterial catheter system was effective in delivering cells to the kidney and permitted repeated injection of cells.

Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.

PubMed

Teichert, Axel; Brossard, Patrick; Felber Medlin, Loyse; Sandalic, Larissa; Franzon, Mikael; Wynne, Chris; Laugesen, Murray; Lüdicke, Frank

2018-03-06

Novel nicotine delivery systems represent an evolving part of the tobacco harm reduction strategy. The pharmacokinetic (PK) profile of nicotine delivered by P3L, a pulmonary nicotine delivery system, and its effects on smoking urges and craving relief in relation to Nicorette inhalator were evaluated. This open-label, ascending nicotine levels study was conducted in 16 healthy smokers. Three different nicotine delivery levels, 50, 80, and 150 µg/puff, delivered by the P3L system were evaluated consecutively on different days after the use of the Nicorette inhalator. Venous nicotine PK, subjective effects, and tolerability were assessed. Geometric least-squares means for maximum plasma nicotine concentration (Cmax), generated by the mixed-effect model for exposure comparison, were 9.7, 11.2, and 9.8 ng/mL for the 50, 80, and 150 µg/puff P3L variants, respectively, compared to 6.1 ng/mL after Nicorette inhalator use. Median time from product use start to Cmax was 7.0 minutes for all P3L, compared to 30.0 minutes for the Nicorette inhalator. Craving reduction was slightly faster than with the Nicorette inhalator as assessed with the visual analog scale craving score. The mean Questionnaire of Smoking Urges -brief total scores did not differ for both products. P3L was well tolerated. At all three nicotine levels tested, the inhalation of the nicotine lactate aerosol delivered with the P3L provided plasma nicotine concentrations higher and faster compared to the Nicorette inhalator. The plasma nicotine concentration-time profile supports a pulmonary route of absorption for P3L compared to the oromucosal absorption of the Nicorette inhalator. The combination of nicotine and lactic acid with the P3L device shows potential over existing nicotine delivery systems by delivering nicotine with kinetics close to published data on conventional cigarettes and without exogenous carrier substances as used in current electronic nicotine delivery systems. Altogether, the PK profile, subjective effects, and safety profile obtained in this study suggest P3L is an innovative nicotine delivery product that will be acceptable to adult smokers as an alternative to cigarettes.

A Comparative Study of Language Instructional Delivery System between Nursery Schools in Rural and Urban Areas in Osun State

ERIC Educational Resources Information Center

Odejobi, Cecilia Omobola

2014-01-01

The study compared the language instructional delivery system between the nursery schools in rural and urban areas in Osun state. The population consisted of all the nursery school teachers in Osun state. Proportionate random sampling was used to prune down the population. In all 130 nursery school teachers, 68 in urban areas and 62 in rural areas…

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.

Is Student Performance on the Information Systems Analyst Certification Exam Affected by Form of Delivery of Information Systems Coursework?

ERIC Educational Resources Information Center

Haga, Wayne; Moreno, Abel; Segall, Mark

2012-01-01

In this paper, we compare the performance of Computer Information Systems (CIS) majors on the Information Systems Analyst (ISA) Certification Exam. The impact that the form of delivery of information systems coursework may have on the exam score is studied. Using a sample that spans three years, we test for significant differences between scores…

Local delivery of fluorescent dye for fiber-optics confocal microscopy of the living heart.

PubMed

Huang, Chao; Kaza, Aditya K; Hitchcock, Robert W; Sachse, Frank B

2014-01-01

Fiber-optics confocal microscopy (FCM) is an emerging imaging technology with various applications in basic research and clinical diagnosis. FCM allows for real-time in situ microscopy of tissue at sub-cellular scale. Recently FCM has been investigated for cardiac imaging, in particular, for discrimination of cardiac tissue during pediatric open-heart surgery. FCM relies on fluorescent dyes. The current clinical approach of dye delivery is based on systemic injection, which is associated with high dye consumption, and adverse clinical events. In this study, we investigated approaches for local dye delivery during FCM imaging based on dye carriers attached to the imaging probe. Using three-dimensional confocal microscopy, automated bench tests, and FCM imaging we quantitatively characterized dye release of carriers composed of open-pore foam only and foam loaded with agarose hydrogel. In addition, we compared local dye delivery with a model of systemic dye delivery in the isolated perfused rodent heart. We measured the signal-to-noise ratio (SNR) of images acquired in various regions of the heart. Our evaluations showed that foam-agarose dye carriers exhibited a prolonged dye release vs. foam-only carriers. Foam-agarose dye carriers allowed reliable imaging of 5-9 lines, which is comparable to 4-8 min of continuous dye release. Our study in the living heart revealed that the SNR of FCM images using local and systemic dye delivery is not different. However, we observed differences in the imaged tissue microstructure with the two approaches. Structural features characteristic of microvasculature were solely observed for systemic dye delivery. Our findings suggest that local dye delivery approach for FCM imaging constitutes an important alternative to systemic dye delivery. We suggest that the approach for local dye delivery will facilitate clinical translation of FCM, for instance, for FCM imaging during pediatric heart surgery.

Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies.

PubMed

Estracanholli, Eder André; Praça, Fabíola Silva Garcia; Cintra, Ana Beatriz; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

2014-12-01

Liquid crystalline systems of monoolein/water could be a promising approach for the delivery of celecoxib (CXB) to the skin because these systems can sustain drug release, improve drug penetration into the skin layers and minimize side effects. This study evaluated the potential of these systems for the delivery of CXB into the skin based on in vitro drug release and skin permeation studies. The amount of CXB that permeated into and/or was retained in the skin was assayed using an HPLC method. Polarizing light microscopy studies showed that liquid crystalline systems of monoolein/water were formed in the presence of CXB, without any changes in the mesophases. The liquid crystalline systems decreased drug release when compared to control solution. Drug release was independent of the initial water content of the systems and CXB was released from cubic phase systems, irrespective of the initial water content. The systems released the CXB following zero-order release kinetics. In vitro drug permeation studies showed that cubic phase systems allowed drug permeation and retention in the skin layers. Cubic phase systems of monoolein/water may be promising vehicles for the delivery of CXB in/through the skin because it improved CXB skin permeation compared with the control solution.

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.

Calculating length of gestation from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database versus vital records may alter reported rates of prematurity.

PubMed

Stern, Judy E; Kotelchuck, Milton; Luke, Barbara; Declercq, Eugene; Cabral, Howard; Diop, Hafsatou

2014-05-01

To compare length of gestation after assisted reproductive technology (ART) as calculated by three methods from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and vital records (birth and fetal death) in the Massachusetts Pregnancy to Early Life Longitudinal Data System (PELL). Historical cohort study. Database linkage analysis. Live or stillborn deliveries. None. ART deliveries were linked to live birth or fetal death certificates. Length of gestation in 7,171 deliveries from fresh autologous ART cycles (2004-2008) was calculated and compared with that of SART CORS with the use of methods: M1 = outcome date - cycle start date; M2 = outcome date - transfer date + 17 days; and M3 = outcome date - transfer date + 14 days + day of transfer. Generalized estimating equation models were used to compare methods. Singleton and multiple deliveries were included. Overall prematurity (delivery <37 weeks) varied by method of calculation: M1 29.1%; M2 25.6%; M3 25.2%; and PELL 27.2%. The SART methods, M1-M3, varied from those of PELL by ≥ 3 days in >45% of deliveries and by more than 1 week in >22% of deliveries. Each method differed from each other. Estimates of preterm birth in ART vary depending on source of data and method of calculation. Some estimates may overestimate preterm birth rates for ART conceptions. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

National Initiatives to Improve Healthcare Outcomes: A Comparative Study of Health Delivery Systems in Slovakia and the United States.

PubMed

Curtis, Robert; Caplanova, Anetta; Novak, Marcel

2015-01-01

While the United States and Slovakia offer different healthcare delivery systems, each country faces the same challenges of improving the health status of their populations. The authors explore the impact of their respective systems on the health of their populations and compare the health outcomes of both nations. They point out that socioeconomic factors play a far more important role in determining population health outcomes than do the structures of the systems surrounding the care delivery. The authors illustrate this finding through a comparison of the poverty and education levels of a selected minority group from each country in relation to the health outcomes for each population group. The comparison reveals that education is a more influential determinant in a population's health outcomes, than the improved access to care offered by a universal system.

Fast-dissolve drug delivery systems.

PubMed

Habib, W; Khankari, R; Hontz, J

2000-01-01

Fast-dissolve drug delivery is a rapidly growing area in the pharmaceutical industry. This paper defines the technology, discusses its benefits, and reviews and compares various fast-dissolve technologies currently available on the market.

Mesoporous carbon nanomaterials in drug delivery and biomedical application.

PubMed

Zhao, Qinfu; Lin, Yuanzhe; Han, Ning; Li, Xian; Geng, Hongjian; Wang, Xiudan; Cui, Yu; Wang, Siling

2017-01-01

Recent development of nano-technology provides highly efficient and versatile treatment methods to achieve better therapeutic efficacy and lower side effects of malignant cancer. The exploration of drug delivery systems (DDSs) based on nano-material shows great promise in translating nano-technology to clinical use to benefit patients. As an emerging inorganic nanomaterial, mesoporous carbon nanomaterials (MCNs) possess both the mesoporous structure and the carbonaceous composition, endowing them with superior nature compared with mesoporous silica nanomaterials and other carbon-based materials, such as carbon nanotube, graphene and fullerene. In this review, we highlighted the cutting-edge progress of carbon nanomaterials as drug delivery systems (DDSs), including immediate/sustained drug delivery systems and controlled/targeted drug delivery systems. In addition, several representative biomedical applications of mesoporous carbon such as (1) photo-chemo synergistic therapy; (2) delivery of therapeutic biomolecule and (3) in vivo bioimaging are discussed and integrated. Finally, potential challenges and outlook for future development of mesoporous carbon in biomedical fields have been discussed in detail.

Dynamics and fragmentation of thick-shelled microbubbles.

PubMed

May, Donovan J; Allen, John S; Ferrara, Katherine W

2002-10-01

Localized delivery could decrease the systemic side effects of toxic chemotherapy drugs. The unique delivery agents we examine consist of microbubbles with an outer lipid coating, an oil layer, and a perfluorobutane gas core. These structures are 0.5-12 microm in radius at rest. Oil layers of these acoustically active lipospheres (AALs) range from 0.3-1.5 microm in thickness and thus the agents can carry a large payload compared to nano-scale drug delivery systems. We show that triacetin-based drug-delivery vehicles can be fragmented using ultrasound. Compared with a lipid-shelled contrast agent, the expansion of the drug-delivery vehicle within the first cycle is similar, and a subharmonic component is demonstrated at an equivalent radius, frequency, and driving pressure. For the experimental conditions explored here, the pulse length required for destruction of the drug-delivery vehicle is significantly greater, with at least five cycles required, compared with one cycle for the contrast agent. For the drug-delivery vehicle, the observed destruction mechanism varies with the initial radius, with microbubbles smaller than resonance size undergoing a symmetric collapse and producing a set of small, equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents larger than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.

System-state and operating condition sensitive control method and apparatus for electric power delivery systems

NASA Technical Reports Server (NTRS)

Burns, III, William Wesley (Inventor); Wilson, Thomas George (Inventor)

1978-01-01

This invention provides a method and apparatus for determining a precise switching sequence for the power switching elements of electric power delivery systems of the on-off switching type and which enables extremely fast transient response, precise regulation and highly stable operation. The control utilizes the values of the power delivery system power handling network components, a desired output characteristic, a system timing parameter, and the externally imposed operating conditions to determine where steady state operations should be in order to yield desired output characteristics for the given system specifications. The actual state of the power delivery system is continuously monitored and compared to a state-space boundary which is derived from the desired equilibrium condition, and from the information obtained from this comparison, the system is moved to the desired equilibrium condition in one cycle of switching control. Since the controller continuously monitors the power delivery system's externally imposed operating conditions, a change in the conditions is immediately sensed and a new equilibrium condition is determined and achieved, again in a single cycle of switching control.

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.

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

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

PubMed

Zandstra, Jurjen; van Beuge, Marike M; Zuidema, Johan; Petersen, Arjen H; Staal, Mark; Duque, Luisa F; Rodriguez, Sergio; Lathuile, Audrey A R; Veldhuis, Gert J; Steendam, Rob; Bank, Ruud A; Popa, Eliane R

2015-10-01

The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney. We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs. Using a rat model of acute kidney injury, subcapsular injection of placebo and rapamycin monodisperse microspheres (monospheres) was compared to subcutaneous injection, mimicking systemic administration. We did not find any adverse effects related to the delivery method. Irrespective of the injection site, a similar low dose of rapamycin was present in the circulation. However, only local intrarenal delivery of rapamycin from monospheres led to decreased macrophage infiltration and a significantly lower amount of myofibroblasts in the kidney, where systemic administration did not. Local delivery of rapamycin did cause a transient increase in the deposition of collagen I, but not of collagen III. We conclude that therapeutic effects can be increased when rapamycin is delivered subcapsularly by monospheres, which, combined with low systemic concentrations, may lead to an effective intrarenal delivery method.

Quetiapine Nanoemulsion for Intranasal Drug Delivery: Evaluation of Brain-Targeting Efficiency.

PubMed

Boche, Mithila; Pokharkar, Varsha

2017-04-01

To evaluate the possibility of improved drug delivery of quetiapine fumarate (QTP), a nanoemulsion system was developed for intranasal delivery. Effects of different HLBs of Emalex LWIS 10, PEG 400 and Transcutol P, as co-surfactants, were studied on isotropic region of pseudoternary-phase diagrams of nanoemulsion system composed of capmul MCM (CPM) as oil phase, Tween 80 as surfactant and water. Phase behaviour, globule size, transmission electron microscope (TEM) photographs and brain-targeting efficiency of quetiapine nanoemulsion were investigated. In vitro dissolution study of optimised nanoemulsion formulation, with mean diameter 144 ± 0.5 nm, showed more than twofold increase in drug release as compared with pure drug. According to results of in vivo tissue distribution study in Wistar rats, intranasal administration of QTP-loaded nanoemulsion had shorter T max compared with that of intravenous administration. Higher drug transport efficiency (DTE%) and direct nose-to-brain drug transport (DTP%) was achieved by nanoemulsion. The nanoemulsion system may be a promising strategy for brain-targeted delivery of QTP.

42 CFR 447.54 - Maximum allowable and nominal charges.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., any co-payments it imposes under a fee-for-service delivery system do not exceed the amounts shown in... Deductible, Coinsurance, Co-Payment Or Similar Cost-Sharing Charge § 447.54 Maximum allowable and nominal... paragraph (a)(3)(i) of this section for comparable services under a fee-for-service delivery system. When...

42 CFR 447.54 - Maximum allowable and nominal charges.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., any co-payments it imposes under a fee-for-service delivery system do not exceed the amounts shown in... Deductible, Coinsurance, Co-Payment Or Similar Cost-Sharing Charge § 447.54 Maximum allowable and nominal... paragraph (a)(3)(i) of this section for comparable services under a fee-for-service delivery system. When...

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

PubMed

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

2017-07-01

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

In vivo delivery and long-term tissue retention of nano-encapsulated sirolimus using a novel porous balloon angioplasty system.

PubMed

Granada, Juan F; Tellez, Armando; Baumbach, William R; Bingham, Brendan; Keng, Yen-Fang; Wessler, Jeffrey; Conditt, Gerard; McGregor, Jennifer; Stone, Gregg; Kaluza, Greg L; Leon, Martin B

2016-08-20

Among antirestenotic compounds, sirolimus displays a superior safety profile compared to paclitaxel, but its pharmacokinetic properties make it a challenging therapeutic candidate for single-time delivery. Herein we evaluate the feasibility of delivery, long-term retention and vascular effects of sirolimus nanoparticles delivered through a novel porous angioplasty balloon in normal porcine arteries and in a swine model of in-stent restenosis (ISR). Sirolimus nanoparticle formulation was delivered via porous balloon angioplasty to 753 coronary artery segments for pharmacokinetic studies and 26 segments for biological effect of sirolimus delivery in different clinical scenarios (de novo [n=8], ISR [n=6] and following stent implantation [n=12]). Sirolimus coronary artery concentrations were above the target therapeutic level of 1 ng/mg after 26 days, and were >100-fold higher in coronary artery treatment sites than in distal myocardium and remote tissues at all time points. At 28 days, reduction in percent stenosis in formulation-treated sites compared to balloon angioplasty treatment was noted in all three clinical scenarios, with the largest effect seen in the de novo study. Local coronary delivery of sirolimus nanoparticles in the porcine model using a novel porous balloon delivery system achieved therapeutic long-term intra-arterial drug levels without significant systemic residual exposure.

Intrathecal Drug Delivery Systems for Cancer Pain: A Health Technology Assessment

PubMed Central

2016-01-01

Background Intrathecal drug delivery systems can be used to manage refractory or persistent cancer 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 due owing to cancer. Methods We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library databases, 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 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. The cost burden of publicly funding intrathecal drug delivery systems for cancer pain was estimated for a 5-year timeframe using a combination of published literature, information from the device manufacturer, administrative data, and expert opinion for the inputs. Results We included one randomized trial that examined effectiveness and harms, and one case series that reported an eligible economic evaluation. We found very low quality evidence that intrathecal drug delivery systems added to comprehensive pain management reduce overall drug toxicity; no significant reduction in pain scores was observed. Weak conclusions from economic evidence suggested that intrathecal drug delivery systems had the potential to be more cost-effective than high-cost oral therapy if administered for 7 months or longer. The cost burden of publicly funding this therapy is estimated to be $100,000 in the first year, increasing to $500,000 by the fifth year. Conclusions Current evidence could not establish the benefit, harm, or cost-effectiveness of intrathecal drug delivery systems compared with current standards of care for managing refractory cancer pain in adults. Publicly funding intrathecal drug delivery systems for cancer pain would result in a budget impact of several hundred thousand dollars per year. PMID:27026796

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

PubMed

2016-01-01

Intrathecal drug delivery systems can be used to manage refractory or persistent cancer 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 due owing to cancer. We searched Ovid MEDLINE, Ovid Embase, the Cochrane Library databases, 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 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. The cost burden of publicly funding intrathecal drug delivery systems for cancer pain was estimated for a 5-year timeframe using a combination of published literature, information from the device manufacturer, administrative data, and expert opinion for the inputs. We included one randomized trial that examined effectiveness and harms, and one case series that reported an eligible economic evaluation. We found very low quality evidence that intrathecal drug delivery systems added to comprehensive pain management reduce overall drug toxicity; no significant reduction in pain scores was observed. Weak conclusions from economic evidence suggested that intrathecal drug delivery systems had the potential to be more cost-effective than high-cost oral therapy if administered for 7 months or longer. The cost burden of publicly funding this therapy is estimated to be $100,000 in the first year, increasing to $500,000 by the fifth year. Current evidence could not establish the benefit, harm, or cost-effectiveness of intrathecal drug delivery systems compared with current standards of care for managing refractory cancer pain in adults. Publicly funding intrathecal drug delivery systems for cancer pain would result in a budget impact of several hundred thousand dollars per year.

Microencapsulation: A promising technique for controlled drug delivery.

PubMed

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

2010-07-01

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

Microencapsulation: A promising technique for controlled drug delivery

PubMed Central

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

2010-01-01

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

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.

PubMed

Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

2015-05-01

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.

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.

A Framework for Describing Health Care Delivery Organizations and Systems

PubMed Central

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

2015-01-01

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

Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges.

PubMed

Ha, Dinh; Yang, Ningning; Nadithe, Venkatareddy

2016-07-01

Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

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.

Preliminary analysis of hub and spoke air freight distribution system

NASA Technical Reports Server (NTRS)

Whitehead, A. H., Jr.

1978-01-01

A brief analysis is made of the hub and spoke air freight distribution system which would employ less than 15 hub centers world wide with very large advanced distributed-load freighters providing the line-haul delivery between hubs. This system is compared to a more conventional network using conventionally-designed long-haul freighters which travel between numerous major airports. The analysis calculates all of the transportation costs, including handling charges and pickup and delivery costs. The results show that the economics of the hub/spoke system are severely compromised by the extensive use of feeder aircraft to deliver cargo into and from the large freighter terminals. Not only are the higher costs for the smaller feeder airplanes disadvantageous, but their use implies an additional exchange of cargo between modes compared to truck delivery. The conventional system uses far fewer feeder airplanes, and in many cases, none at all. When feeder aircraft are eliminated from the hub/spoke system, however, that system is universally more economical than any conventional system employing smaller line-haul aircraft.

Examining fiscal federalism, regionalization and community-based initiatives in Canada's health care delivery system.

PubMed

Forest, Pierre-Gerlier; Palley, Howard A

2008-01-01

This study focuses on the ability of Canadian provinces to shape in different ways the development of various provincial health delivery systems within the constraints of the mandates of the federal Canada Health Act of 1984 and the fiscal revenues that the provinces receive if they comply with these mandates. In so doing, it will examine the operation of Canadian federalism with respect to various provincial health systems. This study applies a comparative analysis framework developed by Heisler and Peters to facilitate an understanding of the dimensionality of provincial health delivery systems as applied to the case of provincial regionalization and community-based initiatives. The three sets of relationships touched upon are: first, the levels of government and the nature of their involvement in public policy concerning the provincial health care delivery systems; and secondly, understanding of the factors influencing provincial governments' political dispositions to act in various directions. A third dimension that is taken are the factors influencing the "timing" of particular decisions. A fourth area noted by Heisler and Peters and other comparative analysts is the nature and characteristics of public and private sector activities in health care and other social policy areas. While the evolving nature of public and private sector health care delivery activities within Canada's provincial and territorial systems is a significant policy matter in the Canadian context, due to the space limitations of this article, they are not discussed herein.

Laboratory formulated magnetic nanoparticles for enhancement of viral gene expression in suspension cell line.

PubMed

Bhattarai, Shanta Raj; Kim, Sun Young; Jang, Kyu Yun; Lee, Ki Chang; Yi, Ho Keun; Lee, Dae Yeol; Kim, Hak Yong; Hwang, Pyoung Han

2008-02-01

One factor critical to successful gene therapy is the development of efficient delivery systems. Although advances in gene transfer technology including viral and non-viral vectors have been made, an ideal vector system has not yet been constructed. Due to the growing concerns over the toxicity and immunogenicity of viral DNA delivery systems, DNA delivery via improve viral routes has become more desirable and advantageous. The ideal improve viral DNA delivery system should be a synthetic materials plus viral vectors. The materials should also be biocompatible, efficient, and modular so that it is tunable to various applications in both research and clinical settings. The successful steps towards this improve viral DNA delivery system is demonstrated: a magnetofection system mediated by modified cationic chitosan-coated iron oxide nanoparticles. Dense colloidal cationic iron oxide nanoparticles serve as an uptake-enhancing component by physical concentration at the cell surface in presence of external magnetic fields; enhanced viral gene expression (3-100-fold) due to the particles is seen as compared to virus vector alone with little virus dose.

Oral Insulin Delivery: How Far Are We?

PubMed Central

Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

2013-01-01

Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

Electrostatic wrapping of doxorubicin with curdlan to construct an efficient pH-responsive drug delivery system

NASA Astrophysics Data System (ADS)

Zhou, Jiang-Ling; Song, Fei; Tian, Jia-Feng; Nie, Wu-Cheng; Wang, Xiu-Li; Wang, Yu-Zhong

2017-07-01

The development of environmentally responsive drug delivery systems for the treatment of cancer has attracted particular interest in recent years. However, the enhancement of drug loading capacity and realization of pH-responsive drug delivery remain challenging. Herein, we employ carboxymethyl curdlan as a hydrophilic carrier to wrap doxorubicin (DOX) directly via electrostatic interaction. The sizes of the formed nanoparticles can be simply tuned by changing their feeding ratios. In particular, the nanoparticles are highly stable in aqueous solution without size variation. In vitro drug release and cytotoxicity assays illustrate that this delivery system can release DOX differentially under various environmental conditions and transport it into cell nuclei efficiently, with comparable therapeutic effect to the free drug. These results suggest that the carrying of antitumor drugs by polysaccharide via electrostatic interaction is a simple but effective way to construct a pH-dependent drug delivery platform.

A Transdermal Drug Delivery System Based on LIGA Technology and Soft Lithography

NASA Astrophysics Data System (ADS)

Matteucci, Marco; Perennes, Frederic; Marmiroli, Benedetta; Di Fabrizio, Enzo

2007-01-01

This report presents a transdermal drug delivery system based on LIGA fabricated microparts. It is a portable device combining a magnetically actuated micro gear pump with a microneedle array. The fluidic behaviour of the system is analyzed in order to predict its performance according to the dimension of the microparts and then compared to experimental data. The manufacturing process of both micropump and microneedle array are described.

Accounting Education: A Comparative Study of Perception of Learning Outcomes in Traditional and Online Delivery Systems

ERIC Educational Resources Information Center

Connor, Chun-Mei Lee

2009-01-01

As of 2007, over 20% of all higher education students in the U.S took at least one online course (Allen & Seaman, 2008), and over 200 universities offered some measure of online accounting courses (National Center for Education Statistics, 2008).This study compared the student learning outcomes of traditional and online delivery styles in…

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.

A comparison of organized and traditional health care: implications for health promotion and prospective medicine.

PubMed

Lawrence, D M

2005-01-01

To compare organized and traditional health care delivery systems and their ability to meet several major challenges facing health care in the next 25 years. Analysis of traditional and organized health care systems based on a career spent in organized health care systems. The traditional health care system based on independent autonomous physicians is not able to meet the challenges of current healthcare. Stronger integration and coordination, i.e., organized health care delivery systems are required.

Transdermal solid delivery of epigallocatechin-3-gallate using self-double-emulsifying drug delivery system as vehicle: Formulation, evaluation and vesicle-skin interaction.

PubMed

Hu, Caibiao; Gu, Chengyu; Fang, Qiao; Wang, Qiang; Xia, Qiang

2016-02-01

The present study investigated a self-double-emulsifying drug delivery system loaded with epigallocatechin-3-gallate to improve epigallocatechin-3-gallate skin retention. The long chain solid lipids (cetostearyl alcohol) and macadamia oil were utilized as a carrier to deliver the bioactive ingredient. Response surface methodology was used to optimize the formulation, and the solid lipid to total lipid weight ratio, concentration of epigallocatechin-3-gallate and hydrophilic surfactant on skin retention were found to be the principal factors. The optimum formulation with high encapsulation efficiency (95.75%), self-double-emulsification performance (99.58%) and skin retention (87.24%) were derived from the fitted models and experimentally examined, demonstrating a reasonable agreement between experimental and predicted values. Epigallocatechin-3-gallate-self-double-emulsifying drug delivery system was found to be stable for 3 months. Transdermal studies could explain a higher skin diffusion of epigallocatechin-3-gallate from the self-double-emulsifying drug delivery system compared with EGCG aqueous solution. In vitro cytotoxicity showed that epigallocatechin-3-gallate-self-double-emulsifying drug delivery system did not exert hazardous effect on L929 cells up to 1:10. © The Author(s) 2015.

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.

Transforaminal lumbar interbody graft placement using an articulating delivery arm facilitates increased segmental lordosis with superior anterior and midline graft placement.

PubMed

Shau, David N; Parker, Scott L; Mendenhall, Stephen K; Zuckerman, Scott L; Godil, Saniya S; Devin, Clinton J; McGirt, Matthew J

2015-05-01

Transforaminal lumbar interbody fusion (TLIF) is a frequently performed method of lumbar arthrodesis in patients failing medical management of back and leg pain. Accurate placement of the interbody graft and restoration of lordosis has been shown to be crucial when performing lumbar fusion procedures. We performed a single-surgeon, prospective, randomized study to determine whether a novel articulating versus traditional straight graft delivery arm system allows for superior graft placement and increased lordosis for single-level TLIF. Thirty consecutive patients undergoing single-level TLIF were included and prospectively randomized to one of the 2 groups (articulated vs. straight delivery arm system). Three radiographic characteristics were evaluated at 6-week follow-up: (1) degree of segmental lumbar lordosis at the fused level; (2) the percent anterior location of the interbody graft in disk space; and (3) the distance (mm) off midline of the interbody graft placement. Randomization yielded 16 patients in the articulated delivery arm cohort and 14 in the straight delivery arm cohort. The articulating delivery arm system yielded an average of 14.7-degree segmental lordosis at fused level, 35% anterior location, and 3.6 mm off midline. The straight delivery arm system yielded an average of 10.7-degree segmental lordosis at fused level, 46% anterior location, and 7.0 mm off midline. All 3 comparisons were statistically significant (P<0.05). The study suggests that an articulating delivery arm system facilitates superior anterior and midline TLIF graft placement allowing for increased segmental lordosis compared with a traditional straight delivery arm system.

Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders.

PubMed

Ong, Wei-Yi; Shalini, Suku-Maran; Costantino, Luca

2014-01-01

Many potential drugs for the treatment of neurological diseases are unable to reach the brain in sufficient enough concentrations to be therapeutic because of the blood brain barrier. On the other hand, direct delivery of drugs to the brain provides the possibility of a greater therapeutic-toxic ratio than with systemic drug delivery. The use of intranasal delivery of therapeutic agents to the brain provides a means of bypassing the blood brain barrier in a non-invasive manner. In this respect, nanosized drug carriers were shown to enhance the delivery of drugs to CNS compared to equivalent drug solution formulations. Neurological conditions that have been studied in animal models that could benefit from nose-to-brain delivery of nanotherapeutics include pain, epilepsy, neurodegenerative disease and infectious diseases. The delivery of drugs to the brain via the nose-to-brain route holds great promise, on the basis of preclinical research by means of drug delivery systems such as polymeric nanoparticles and clinical data related to intranasal delivery to CNS of large molecular weight biologics administered in solution, but safety issues about toxicity on nasal mucosa, Np transport into the brain, delivery only to specific brain regions and variability in the adsorbed dose still represent research topics that need to be considered, with a view of clinical translation of these delivery systems.

Augmentative Communication Services in the Schools.

ERIC Educational Resources Information Center

Blackstone, Sarah W.

1989-01-01

The article considers current issues concerning service delivery systems and practices concerning augmentative and alternative communication (AAC) services in U.S. schools. Concerns in AAC program development are noted and service delivery models (center-based, community-based, or collaborative) are compared. (DB)

Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.

PubMed

Jang, Bora; Kwon, Hyokyoung; Katila, Pramila; Lee, Seung Jin; Lee, Hyukjin

2016-03-01

Cancer causes >8.2 million deaths annually worldwide; thus, various cancer treatments have been investigated over the past decades. Among them, combination drug therapy has become extremely popular, and treatment with more than one drug is often necessary to achieve appropriate anticancer efficacy. With the development of nanoformulations and nanoparticulate-based drug delivery, researchers have explored the feasibility of dual delivery of biological therapeutics to overcome the current drawbacks of cancer therapy. Compared with the conventional single drug therapy, dual delivery of therapeutics has provided various synergistic effects in addition to offering multimodality to cancer treatment. In this review, we highlight and summarize three aspects of dual-delivery systems for cancer therapy. These include (1) overcoming drug resistance by the dual delivery of chemical drugs with biological therapeutics for synergistic therapy, (2) targeted and controlled drug release by the dual delivery of drugs with stimuli-responsive nanomaterials, and (3) multimodal theranostics by the dual delivery of drugs and molecular imaging probes. Furthermore, recent developments, perspectives, and new challenges regarding dual-delivery systems for cancer therapy are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Erythrocyte membrane based cationic polymer-mcDNA complexes as an efficient gene delivery system.

PubMed

Huang, Ping; Zhao, Jing; Wei, Chiju; Hou, Xiaohu; Chen, Pingzhang; Tan, Yan; He, Cheng-Yi; Wang, Zhiyong; Chen, Zhi-Ying

2016-12-20

Gene therapy has great promise for the treatment of obtained and inherited serious diseases. However, the lack of safe and efficient gene delivery systems remains a barrier for their clinical application. Here, we reported a potential gene delivery vehicle composed of the erythrocyte membrane and cationic polymers, for example the XtremeGENE from Roche and the ε-caprolactone modified polyethylenimine. In addition to high efficiency, this system showed negligible cytotoxicity compared to the two cationic polymers alone in various cell lines, including human embryonic kidney cells (293T), human liver cancer cells (Huh7 and HepG2), murine dendritic cells (DC2.4) and human umbilical cord mesenchymal stem cells (Hu-MSCs). Moreover, the results of confocal laser scanning microscopy and flow cytometry suggested that the cell uptake of this gene vector was improved and might be introduced by the fusion interaction between the erythrocyte membrane and targeted cells.Thus, all the results revealed that the erythrocyte membrane based gene delivery system might be able to serve as an excellent gene delivery system.

Topical delivery of roxithromycin solid-state forms entrapped in vesicles.

PubMed

Csongradi, Candice; du Plessis, Jeanetta; Aucamp, Marique Elizabeth; Gerber, Minja

2017-05-01

Recently, considerable interest developed in using newer/improved antibiotics for the treatment of Acne vulgaris. During this study, different roxithromycin solid-state forms (i.e. crystalline and amorphous) were encapsulated into vesicle systems (niosomes, proniosomes, ufosomes and pro-ufosomes) for dermis targeted delivery. Characterization of the vesicles was done with transmission electron microscopy, light microscopy, droplet size, droplet size distribution, pH, zeta-potential and entrapment efficiency percentage. Finally, comparative release and topical diffusion studies were performed, to evaluate if targeted topical delivery was obtained and if the roxithromycin solid-state amorphous forms resulted in improved topical delivery. Vesicle systems containing different roxithromycin (2%) solid-state forms were successfully prepared and characterized. The vesicles showed optimal properties for topical delivery. All carrier systems had topical delivery to the epidermis-dermis, whilst no roxithromycin was found in the receptor compartment or stratum corneum-epidermis. The niosomes were the leading formulation and the two amorphous forms had better topical delivery than the crystalline form. Successful targeted delivery of roxithromycin was obtained in the dermis, where the activity against Propionibacterium acnes is needed. The amorphous forms seemed to have held their solid-state form during formulation and in the vesicles, showing improved topical delivery in comparison to the crystalline form. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of free delivery policy on utilization of maternal health services in county referral hospitals in Kenya.

PubMed

Njuguna, John; Kamau, Njoroge; Muruka, Charles

2017-06-21

Kenya has a high maternal mortality rate. Provision of skilled delivery plays a major role in reducing maternal mortality. Cost is a hindrance to the utilization of skilled delivery. The Government of Kenya introduced a policy of free delivery services in government facilities beginning June 2013. We sought to determine the impact of this intervention on facility based deliveries in Kenya. We compared deliveries and antenatal attendance in 47 county referral hospitals and 30 low cost private hospitals not participating in the free delivery policy for 2013 and 2014 respectively. The data was extracted from the Kenya Health Information System. Multiple regression was done to assess factors influencing increase in number of deliveries among the county referral hospitals. The number of deliveries and antenatal attendance increased by 26.8% and 16.2% in county referral hospitals and decreased by 11.9% and 5.4% respectively in low cost private hospitals. Increase in deliveries among county referral hospitals was influenced by population size of county and type of county referral hospital. Counties with level 5 hospitals recorded more deliveries compared to those with level 4 hospitals. This intervention increased the number of facility based deliveries. Policy makers may consider incorporating low cost private hospitals so as to increase the coverage of this intervention.

Nebuliser systems for drug delivery in cystic fibrosis.

PubMed

Daniels, Tracey; Mills, Nicola; Whitaker, Paul

2013-04-30

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

Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment.

PubMed

Barhate, Ganesh; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Pokharkar, Varsha

2014-11-01

Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

In Vivo Tumor Gene Delivery Using Novel Peptideticles: pH-Responsive and Ligand Targeted Core-Shell Nanoassembly.

PubMed

Alipour, Mohsen; Majidi, Asia; Molaabasi, Fatemeh; Sheikhnejad, Reza; Hosseinkhani, Saman

2018-04-30

Modulating cancer causing genes with nucleic acid based-molecules as cutting-edge approaches need efficient delivery systems to succeed in clinic. Herein, we report design and fabrication of a novel tissue penetrating Peptideticle with charge-structure switching in tumor microenvironment for an effective gene delivery. The comparative in vitro studies indicate that peptideticles identify and bind to tumor endothelial cells and efficiently penetrate into multicellular tumor spheroid. In addition, negatively charged peptideticle at pH 7.4, prevent unwanted interaction while it's sharp charge-structure switching at pH 6.2-6.9 (e.g.in tumor tissue) facilitates malignant cells penetration. More importantly, upon systemic administration into tumor bearing mice, peptideticles effectively localized in tumor tissue and delivered luciferase gene with a 200-fold higher efficiency compared to their non-pH-responsive counterparts. In conclusion, this study presents a robust nanoassembly of safe materials for high efficient tumor gene delivery. This article is protected by copyright. All rights reserved. © 2018 UICC.

Local vs. systemic administration of bisphosphonates in rat cleft bone graft: A comparative study

PubMed Central

Lin, Lawrence; Olson, Jeffrey; Kwon, Taewoo; Bezouglaia, Olga; Tran, Jaime; Hoang, Michael; Bui, Kimberly; Kim, Reuben H.; Tetradis, Sotirios

2018-01-01

A majority of patients with orofacial cleft deformity requires cleft repair through a bone graft. However, elevated amount of bone resorption and subsequent bone graft failure remains a significant clinical challenge. Bisphosphonates (BPs), a class of anti-resorptive drugs, may offer great promise in enhancing the clinical success of bone grafting. In this study, we compared the effects of systemic and local delivery of BPs in an intraoral bone graft model in rats. We randomly divided 34 female 20-week-old Fischer F344 Inbred rats into four groups to repair an intraoral critical-sized defect (CSD): (1) Control: CSD without graft (n = 4); (2) Graft/Saline: bone graft with systemic administration of saline 1 week post-operatively (n = 10); (3) Graft/Systemic: bone graft with systemic administration of zoledronic acid 1 week post-operatively (n = 10); and (4) Graft/Local: bone graft pre-treated with zoledronic acid (n = 10). At 6-weeks post-operatively, microCT volumetric analysis showed a significant increase in bone fraction volume (BV/TV) in the Graft/Systemic (62.99 ±14.31%) and Graft/Local (69.35 ±13.18%) groups compared to the Graft/Saline (39.18±10.18%). Similarly, histological analysis demonstrated a significant increase in bone volume in the Graft/Systemic (78.76 ±18.00%) and Graft/Local (89.95 ±4.93%) groups compared to the Graft/Saline (19.74±18.89%). The local delivery approach resulted in the clinical success of bone grafts, with reduced graft resorption and enhanced osteogenesis and bony integration with defect margins while avoiding the effects of BPs on peripheral osteoclastic function. In addition, local delivery of BPs may be superior to systemic delivery with its ease of procedure as it involves simple soaking of bone graft materials in BP solution prior to graft placement into the defect. This new approach may provide convenient and promising clinical applications towards effectively managing cleft patients. PMID:29304080

Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

PubMed

Babaei, S; Ghanbarzadeh, S; Adib, Z M; Kouhsoltani, M; Davaran, S; Hamishehkar, H

2016-05-01

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

PubMed

Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

2016-02-10

Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Dosimetric verification of gated delivery of electron beams using a 2D ion chamber array

PubMed Central

Yoganathan, S. A.; Das, K. J. Maria; Raj, D. Gowtham; Kumar, Shaleen

2015-01-01

The purpose of this study was to compare the dosimetric characteristics; such as beam output, symmetry and flatness between gated and non-gated electron beams. Dosimetric verification of gated delivery was carried for all electron beams available on Varian CL 2100CD medical linear accelerator. Measurements were conducted for three dose rates (100 MU/min, 300 MU/min and 600 MU/min) and two respiratory motions (breathing period of 4s and 8s). Real-time position management (RPM) system was used for the gated deliveries. Flatness and symmetry values were measured using Imatrixx 2D ion chamber array device and the beam output was measured using plane parallel ion chamber. These detector systems were placed over QUASAR motion platform which was programmed to simulate the respiratory motion of target. The dosimetric characteristics of gated deliveries were compared with non-gated deliveries. The flatness and symmetry of all the evaluated electron energies did not differ by more than 0.7 % with respect to corresponding non-gated deliveries. The beam output variation of gated electron beam was less than 0.6 % for all electron energies except for 16 MeV (1.4 %). Based on the results of this study, it can be concluded that Varian CL2100 CD is well suitable for gated delivery of non-dynamic electron beams. PMID:26170552

Enhanced Remedial Amendment Delivery to Subsurface Using Shear Thinning Fluid and Aqueous Foam

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

Zhong, Lirong; Szecsody, James E.; Oostrom, Martinus

2011-04-23

A major issue with in situ subsurface remediation is the ability to achieve an even spatial distribution of remedial amendments to the contamination zones in an aquifer or vadose zone. Delivery of amendment to the aquifer using shear thinning fluid and to the vadose zone using aqueous foam has the potential to enhance the amendment distribution into desired locations and improve the remediation. 2-D saturated flow cell experiments were conducted to evaluate the enhanced sweeping, contaminant removal, and amendment persistence achieved by shear thinning fluid delivery. Bio-polymer xanthan gum solution was used as the shear thinning fluid. Unsaturated 1-D columnmore » and 2-D flow cell experiments were conducted to evaluate the mitigation of contaminant mobilization, amendment uniform distribution enhancement, and lateral delivery improvement by foam delivery. Surfactant sodium lauryl ether sulfate was used as the foaming agent. It was demonstrated that the shear thinning fluid injection enhanced the fluid sweeping over a heterogeneous system and increased the delivery of remedial amendment into low-permeability zones. The persistence of the amendment distributed into the low-perm zones by the shear thinning fluid was prolonged compared to that of amendment distributed by water injection. Foam delivery of amendment was shown to mitigate the mobilization of highly mobile contaminant from sediments under vadose zone conditions. Foam delivery also achieved more uniform amendment distribution in a heterogeneous unsaturated system, and demonstrated remarkable increasing in lateral distribution of the injected liquid compared to direct liquid injection.« less

Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

NASA Astrophysics Data System (ADS)

Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

2016-06-01

The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

Qualification of the GASGUARD® SAS GGT Arsine Sub-Atmospheric Gas Delivery System for Ion Implantation

NASA Astrophysics Data System (ADS)

Dunn, James P.; Rolland, James L.; Grim, James S.; Machado, Reinaldo M.; Hartz, Christopher L.

2006-11-01

A beta level evaluation of the GASGUARD® SAS GGT Arsine ion implant dopant supply developed by Air Products and Chemicals, Inc. was conducted by Atmel Corporation. The evaluation included characterization of the normalized wafer yield, mass spectra, ionization efficiency, flow rate, beam current, extraction of usable material and cylinder lifetime. This new and novel sub-atmospheric dopant gas delivery system utilizes a unique electrochemical process, which can generate, on demand, high flows of arsine at a constant 400 torr pressure while limiting net inventory of arsine to only 1 gram. This paper illustrates how Atmel Corporation evaluated and released this new arsine dopant delivery system for commercial production and verified high delivery capacity, resulting in reduced gas costs and increased cylinder life compared to the traditional adsorbent based technology.

Chitosan-functionalised single-walled carbon nanotube-mediated drug delivery of SNX-2112 in cancer cells.

PubMed

Zheng, Lixia; Wu, Shao; Tan, Li; Tan, Huo; Yu, Baodan

2016-09-01

Delivery of amphiphobic drugs (insoluble in both water and oil) has been a great challenge in drug delivery. SNX-2112, a novel inhibitor of Hsp90, is a promising drug candidate for treating various types of cancers; however, the insolubility greatly limits its clinical application. This study aimed to build a new type of drug delivery system using single-walled carbon nanotubes (SWNTs) for controllable release of SNX-2112; chitosan (CHI) was non-covalently added to SWNTs to improve their biocompatibility. SWNTs-CHI demonstrated high drug-loading capability; the release of SNX-2112 was pH triggered and time related. The intracellular reactive oxygen species of SWNTs-CHI increased, compared with that of SWNTs, leading to higher mitogen-activated protein kinase and cell apoptosis. The results of western-blotting, lactate dehydrogenase (LDH) release assay, and cell viability assay analyses indicated that apoptosis-related proteins were abundantly expressed in K562 cells and that the drug delivery system significantly inhibited K562 cells. Thus, SWNT-CHI/SNX-2112 shows great potential as a drug delivery system for cancer therapy. © The Author(s) 2016.

The potential of polymeric film-forming systems as sustained delivery platforms for topical drugs.

PubMed

Frederiksen, Kit; Guy, Richard H; Petersson, Karsten

2016-01-01

Dosing regimens requiring multiple daily applications frequently result in poor patient compliance, especially in the treatment of chronic skin diseases. Consequently, development of sustained delivery systems for topical drugs permitting less frequent dosing is of continuing interest for dermatological therapy. This potential of polymeric film-forming systems (FFS), created in situ on the skin, as sustained delivery platforms for topical drug delivery is reviewed. Key formulation parameters that determine delivery efficiency are considered focussing on those that permit a drug reservoir to be established in the upper layers of the skin and/or on the skin surface from which release can be sustained over a prolonged period. The advantageous and superior cosmetic attributes of FFS (compared to conventional semi-solid formulations) that offer significantly improved patient compliance are also addressed. The promise of polymeric FFS as convenient and aesthetic platforms for sustained topical drug delivery is clear. Manipulation of the formulation allows the delivery profile to be customized and optimized to take advantage of both a rapid, initial input of drug into the skin (likely due to a transient period of supersaturation) and a slower, controlled release over an extended time from the residual film created thereafter.

A novel gene delivery composite system based on biodegradable folate-poly (ester amine) polymer and thermosensitive hydrogel for sustained gene release

PubMed Central

Yang, Yi; Zhao, Hang; Jia, YanPeng; Guo, QingFa; Qu, Ying; Su, Jing; Lu, XiaoLing; Zhao, YongXiang; Qian, ZhiYong

2016-01-01

Local anti-oncogene delivery providing high local concentration of gene, increasing antitumor effect and decreasing systemic side effects is currently attracting interest in cancer therapy. In this paper, a novel local sustained anti-oncogene delivery system, PECE thermoresponsive hydrogel containing folate-poly (ester amine) (FA-PEA) polymer/DNA (tumor suppressor) complexes, is demonstrated. First, a tumor-targeted biodegradable folate-poly (ester amine) (FA-PEA) polymer based on low-molecular-weight polyethyleneimine (PEI) was synthesized and characterized, and the application for targeted gene delivery was investigated. The polymer had slight cytotoxicity and high transfection efficiency in vitro compared with PEI 25k, which indicated that FA-PEA was a potential vector for targeted gene delivery. Meanwhile, we successfully prepared a thermoresponsive PECE hydrogel composite containing FA-PEA/DNA complexes which could contain the genes and slowly release the genes into cells. We concluded the folate-poly (ester amine) (FA-PEA) polymer would be useful for targeted gene delivery, and the novel gene delivery composite based on biodegradable folate-poly (ester amine) polymer and thermosensitive PECE hydrogel showed potential for sustained gene release. PMID:26883682

Nanocarriers for cancer-targeted drug delivery.

PubMed

Kumari, Preeti; Ghosh, Balaram; Biswas, Swati

2016-01-01

Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.

Conductive polymer nanotube patch for fast and controlled ex vivo transdermal drug delivery.

PubMed

Nguyen, Thao M; Lee, Sebin; Lee, Sang Bok

2014-10-01

To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems.

Perinatal mortality among infants born during health user-fees (Cash & Carry) and the national health insurance scheme (NHIS) eras in Ghana: a cross-sectional study.

PubMed

Ibrahim, Abdallah; Maya, Ernest T; Donkor, Ernestina; Agyepong, Irene A; Adanu, Richard M

2016-12-08

This research determined the rates of perinatal mortality among infants delivered under Ghana's national health insurance scheme (NHIS) compared to infants delivered under the previous "Cash and Carry" system in Northern Region, especially as the country takes stock of its progress toward meeting the Millennium Development Goals (MDG) 4 and 5. The labor and maternity wards delivery records of infants delivered before and after the implementation of the NHIS in Northern Region were examined. Records of available daily deliveries during the two health systems were extracted. Fisher's exact tests of non-random association were used to examine the bivariate association between categorical independent variables and perinatal mortality. On average, 8% of infants delivered during the health user-fee (Cash & Carry) died compared to about 4% infant deaths during the NHIS delivery fee exemption period in Northern Region, Ghana. There were no remarkable difference in the rate of infant deaths among mothers in almost all age categories in both the Cash and Carry and the NHIS periods except in mothers age 35 years and older. Infants born to multiparous mothers were significantly more likely to die than those born to first time mothers. There were more twin deaths during the Cash and Carry system (p = 0.001) compared to the NHIS system. Deliveries by caesarean section increased from an average of 14% in the "Cash and Carry" era to an average of 20% in the NHIS era. The overall rate of perinatal mortality declined by half (50%) in infants born during the NHIS era compared to the Cash and Carry era. However, caesarean deliveries increased during the NHIS era. These findings suggest that pregnant women in the Northern Region of Ghana were able to access the opportunity to utilize the NHIS for antenatal visits and possibly utilized skilled care at delivery at no cost or very minimal cost to them, which therefore improved Ghana's progress towards meeting the MDG 4, (reducing under-five deaths by two-thirds).

Continuum of Care Services for Maternal and Child Health using mobile technology - a health system strengthening strategy in low and middle income countries.

PubMed

Balakrishnan, Ramkrishnan; Gopichandran, Vijayaprasad; Chaturvedi, Sharadprakash; Chatterjee, Rahul; Mahapatra, Tanmay; Chaudhuri, Indrajit

2016-07-07

Mobile phone technology is utilized for better delivery of health services worldwide. In low-and-middle income countries mobile phones are now ubiquitous. Thus leveraging mHealth applications in health sector is becoming popular rapidly in these countries. To assess the effectiveness of the Continuum of Care Services (CCS) mHealth platform in terms of strengthening the delivery of maternal and child health (MCH) services in a district in Bihar, a resource-poor state in India. The CommCare mHealth platform was customized to CCS as one of the innovations under a project funded by the Bill and Melinda Gates Foundation to improve the maternal and newborn health services in Bihar. The intervention was rolled out in one project district in Bihar, during July 2012. More than 550 frontline workers out of a total of 3000 including Accredited Social Health Activists, Anganwadi Workers, Auxilliary Nurse Midwives and Lady Health Supervisors were trained to use the mHealth platform. The service delivery components namely early registration of pregnant women, three antenatal visits, tetanus toxoid immunization of the mother, iron and folic acid tablet supply, institutional delivery, postnatal home visits and early initiation of breastfeeding were used as indicators for good quality services. The resultant coverage of these services in the implementation area was compared with rest of Bihar and previous year statistics of the same area. The time lag between delivery of a service and its record capture in the maternal and child tracking system (MCTS) database was computed in a random sample of 16,000 beneficiaries. The coverage of services among marginalized and non-marginalized castes was compared to indicate equity of service delivery. Health system strengthening was viewed from the angle of coverage, quality, equity and efficiency of services. The implementation blocks had higher coverage of all the eight indicator services compared to rest of Bihar and the previous year. There was equity of services across castes for all the indicators. Timely capture of data was also ensured compared to paper-based reporting. By virtue of its impact on quality, efficiency and equity of service delivery, health care manpower efficiency and governance, the mHealth inclusion at service provision level can be one of the potential strategy to strengthen the health system.

The role of public insurance and the public delivery system in improving birth outcomes for low-income pregnant women.

PubMed

Susan Marquis, M; Long, Stephen H

2002-11-01

Insurance expansions and service delivery system expansions are alternative policy instruments used to try to improve birth outcomes for low-income women. The objective of this research is to investigate the effect of expansions of public insurance on access and birth outcomes for pregnant women and the role of different delivery systems in these outcomes. The experience in Florida during the years 1989-1994 is studied. Data are from linked birth certificates, hospital discharge data, Medicaid eligibility and claims files, and county health department records. Use of prenatal care and birthweight for low-income women is compared under different financing for prenatal care and for those using different delivery systems. Several approaches to control for self-selection are adopted, and similar results are obtained with each. Women enrolled in Medicaid have more prenatal care visits than the uninsured. Outcomes for those on Medicaid and the uninsured are significantly better if they receive care in the public health system than if they receive care in the private system-including private offices, clinics, and HMOs. Over time, the gap in outcomes between those in the public system and those receiving prenatal care from private physicians has diminished. Public insurance improves access to services, but the delivery system is a key factor in improving outcomes.

Construction of Hyaluronic Tetrasaccharide Clusters Modified Polyamidoamine siRNA Delivery System.

PubMed

Ma, Yingcong; Sha, Meng; Cheng, Shixuan; Yao, Wang; Li, Zhongjun; Qi, Xian-Rong

2018-06-14

The CD44 protein, as a predominant receptor for hyaluronan (HA), is highly expressed on the surface of multiple tumor cells. HA, as a targeting molecule for a CD44-contained delivery system, increases intracellular drug concentration in tumor tissue. However, due to the weak binding ability of hyaluronan oligosaccharide to CD44, targeting for tumor drug delivery has been restricted. In this study, we first use a HA tetrasaccharide cluster as the target ligand to enhance the binding ability to CD44. A polyamidoamine (PAMAM) dendrimer was modified by a HA tetrasaccharide cluster as a nonviral vector for small interfering RNA (siRNA) delivery. The dendrimer/siRNA nanocomplexes increased the cellular uptake capacity of siRNA through the CD44 receptor-mediated endocytosis pathway, allowing the siRNA to successfully escape the endosome/lysosome. Compared with the control group, nanocomplexes effectively reduced the expression of GFP protein and mRNA in MDA-MB-231-GFP cells. This delivery system provides a foundation to increase the clinical applications of PAMAM nanomaterials.

Leveraging socially networked mobile ICT platforms for the last-mile delivery problem.

PubMed

Suh, Kyo; Smith, Timothy; Linhoff, Michelle

2012-09-04

Increasing numbers of people are managing their social networks on mobile information and communication technology (ICT) platforms. This study materializes these social relationships by leveraging spatial and networked information for sharing excess capacity to reduce the environmental impacts associated with "last-mile" package delivery systems from online purchases, particularly in low population density settings. Alternative package pickup location systems (PLS), such as a kiosk on a public transit platform or in a grocery store, have been suggested as effective strategies for reducing package travel miles and greenhouse gas emissions, compared to current door-to-door delivery models (CDS). However, our results suggest that a pickup location delivery system operating in a suburban setting may actually increase travel miles and emissions. Only once a social network is employed to assist in package pickup (SPLS) are significant reductions in the last-mile delivery distance and carbon emissions observed across both urban and suburban settings. Implications for logistics management's decades-long focus on improving efficiencies of dedicated distribution systems through specialization, as well as for public policy targeting carbon emissions of the transport sector are discussed.

Report of Economics Work Group A.

ERIC Educational Resources Information Center

Moyer, J.; And Others

1992-01-01

This summary of a seminar meeting on economics issues and the "blindness system" addresses the economics of four service delivery models (charity, medical, public provider, and business models) and points to consider in selecting a model (professional specialization, integration, and client roles). A chart compares service delivery principles…

A novel bile salts-lipase polymeric film-infused minitablet system for enhanced oral delivery of cholecalciferol.

PubMed

Braithwaite, Miles C; Choonara, Yahya E; Kumar, Pradeep; Tomar, Lomas K; Du Toit, Lisa C; Pillay, Viness

2016-11-01

Few researchers have investigated the use of multiple physiological enhancers combined with synthetic carriers to augment delivery of nutraceuticals. The current work describes the development of an oral delivery system termed a bioactive association platform (BAP) capable of delivering nutraceutical actives from a formulation framework specifically for enhancing the in vitro and in vivo performance of model vitamin, cholecalciferol (Vitamin D 3 ). Synthesis of a novel triple vitamin minitablet and an optimized bile salt/lipase alginate-glycerin film provided unique oral components for inclusion in a BAP capsule. Component validation and physicochemical characterizations included comparative ex vivo permeability, chemical structure mapping, thermodynamic analysis and magnetic resonance imaging. In vitro dissolution studies of the BAP produced an area under the dissolution curve (AUC) for cholecalciferol release that was 28% greater than a conventional comparator product. A total of 84.01% of cholecalciferol was released from the BAP within 3 h versus only 59% from a comparator. Ex vivo permeation studies revealed superior cholecalciferol membrane diffusion from the triple vitamin minitablet BAP component. In vivo performance showed a greater mean change from baseline cholecalciferol to peak plasma levels (C max ) from the BAP compared to the comparator (55.66 versus 46.05 ng/mL). Cholecalciferol bioavailability was improved in vivo with an AUC 0-inf from the BAP that was 3.2× greater than the conventional product. The BAP was also superior at improving and maintaining serum levels of the main metabolite, 25-hydroxyvitamin D 3 , compared to the conventional system. In vitro and in vivo results thus confirmed improvements in cholecalciferol dissolution, membrane permeability and plasma drug levels. The study results position the BAP as an ideal oral vehicle for enhanced delivery of cholecalciferol.

Numerical Comparison of Nasal Aerosol Administration Systems for Efficient Nose-to-Brain Drug Delivery.

PubMed

Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Chan, Hak-Kim; Tu, Jiyuan

2017-12-29

Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

Characterization and Application of a Nose-Only Exposure Chamber for Inhalation Delivery of Liposomal Drugs and Nucleic Acids to Mice

PubMed Central

Seshadri, S.; Garbuzenko, O.B.; Han, T.; Wang, Z.; Minko, T.

2013-01-01

Abstract Background A small nose-only exposure chamber was evaluated for inhalation delivery of drug carrier systems (DCSs) to mice for the treatment of lung cancer. The chamber then was used for inhalation delivery of an anticancer drug, antisense oligonucleotides (ASO), and small interfering RNA (siRNA) directly to the cancerous lungs of mice. Methods The uniformity of particle delivery across the ports of the exposure chamber and stability of the DCS (liposomes) during continuous aerosolization by a Collison nebulizer were examined. The mean produced particle size by number was approximately 130 nm, and the mass median diameter was approximately 270 nm. The system was then used to deliver DCS containing doxorubicin (DOX) and ASO or siRNA targeted to multidrug resistance-associated protein 1 (MRP1) mRNA as suppressors of cancer cell resistance. The retention of the drug in the lungs and the effect on tumor size were compared after inhalation delivery and intravenous injection in a nu/nu mouse model of lung cancer. Results The aerosol mass across the four inhalation ports had a coefficient of variation of less than 12%, and approximately 1.4% of the nebulized mass was available for inhalation at each port. The mean size of 130 nm of liposomal DCS did not change significantly during continuous 60-min aerosolization. For inhalation delivery of DCS with DOX+ASO/siRNA, the amount of drugs available for inhalation was lower compared with intravenous injection of DOX; however, the observed lung dose and the retention time were significantly higher. The delivery of DOX+ASO/siRNA via inhalation resulted in tumor volume reduction of more than 90%, whereas only about 40% reduction was achieved after intravenous injection of DOX. Conclusions The investigated exposure system is suitable for inhalation delivery of complex DCS, and its use to deliver DCS containing anticancer drugs and resistance suppressors via inhalation offered a superior method for lung cancer treatment in mice compared with intravenous injections. PMID:23530772

CD-ROM versus Online.

ERIC Educational Resources Information Center

Wiedemer, John David; Boelio, David B.

1995-01-01

Compares compact discs (CD-ROMs) and online services in terms of cost of information delivery; system advantages and disadvantages; future possibilities; and role in the National Information Infrastructure. Analysis reveals that CD-ROMs have the lowest information delivery cost and are endorsed by the marketplace as a cost-effective way to deliver…

Accuracy of Blood Loss Measurement during Cesarean Delivery.

PubMed

Doctorvaladan, Sahar V; Jelks, Andrea T; Hsieh, Eric W; Thurer, Robert L; Zakowski, Mark I; Lagrew, David C

2017-04-01

Objective  This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design  In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland-Altman method. Results  Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R 2  = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R 2  = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R 2  = 0.304). Conclusion  During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes.

Accuracy of Blood Loss Measurement during Cesarean Delivery

PubMed Central

Doctorvaladan, Sahar V.; Jelks, Andrea T.; Hsieh, Eric W.; Thurer, Robert L.; Zakowski, Mark I.; Lagrew, David C.

2017-01-01

Objective This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland–Altman method. Results Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R2 = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R2 = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R2 = 0.304). Conclusion During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes. PMID:28497007

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

PubMed

Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

2015-01-01

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

Chlorotoxin-conjugated graphene oxide for targeted delivery of an anticancer drug

PubMed Central

Wang, Hao; Gu, Wei; Xiao, Ning; Ye, Ling; Xu, Qunyuan

2014-01-01

Current chemotherapy for glioma is rarely satisfactory due to low therapeutic efficiency and systemic side effects. We have developed a glioma-targeted drug delivery system based on graphene oxide. Targeted peptide chlorotoxin-conjugated graphene oxide (CTX-GO) sheets were successfully synthesized and characterized. Doxorubicin was loaded onto CTX-GO (CTX-GO/DOX) with high efficiency (570 mg doxorubicin per gram CTX-GO) via noncovalent interactions. Doxorubicin release was pH-dependent and showed sustained-release properties. Cytotoxicity experiments demonstrated that CTX-GO/DOX mediated the highest rate of death of glioma cells compared with free doxorubicin or graphene oxide loaded with doxorubicin only. Further, conjugation with chlorotoxin enhanced accumulation of doxorubicin within glioma cells. These findings indicate that CTX-GO is a promising platform for drug delivery and provide a rationale for developing a glioma-specific drug delivery system. PMID:24672236

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…

Biodegradable polymers as non-viral carriers for plasmid DNA delivery.

PubMed

Luten, Jordy; van Nostrum, Cornelus F; De Smedt, Stefaan C; Hennink, Wim E

2008-03-03

Gene therapy holds a great promise for the treatment of acquired and inherited diseases with a genetic origin that are currently incurable. Non-viral gene delivery systems are gaining recognition as an alternative to viral gene vectors for their potential in avoiding immunogenicity and toxicity problems inherently associated with the use of viral systems. Many cationic polymers have been studied both in vitro and in vivo for gene delivery purposes. However, in recent years there has been a focus on biodegradable carrier systems. The potential advantage of biodegradable carriers as compared to their non-degradable counterparts is their reduced toxicity and the avoidance of accumulation of the polymer in the cells after repeated administration. Also, the degradation of the polymer can be used as a tool to release the plasmid DNA into the cytosol. In this article the recent results obtained with two classes of degradable gene delivery systems, namely those based on water-soluble cationic polymers and on micro- and nanoparticles will be summarized and discussed.

3D printed drug delivery and testing systems - a passing fad or the future?

PubMed

Lim, Seng Han; Kathuria, Himanshu; Tan, Justin Jia Yao; Kang, Lifeng

2018-05-18

The US Food and Drug Administration approval of the first 3D printed tablet in 2015 has ignited growing interest in 3D printing, or additive manufacturing (AM), for drug delivery and testing systems. Beyond just a novel method for rapid prototyping, AM provides key advantages over traditional manufacturing of drug delivery and testing systems. These includes the ability to fabricate complex geometries to achieve variable drug release kinetics; ease of personalising pharmacotherapy for patient and lowering the cost for fabricating personalised dosages. Furthermore, AM allows fabrication of complex and micron-sized tissue scaffolds and models for drug testing systems that closely resemble in vivo conditions. However, there are several limitations such as regulatory concerns that may impede the progression to market. Here, we provide an overview of the advantages of AM drug delivery and testing, as compared to traditional manufacturing techniques. Also, we discuss the key challenges and future directions for AM enabled pharmaceutical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Overcoming the Cutaneous Barrier with Microemulsions

PubMed Central

Lopes, Luciana B.

2014-01-01

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

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

PubMed Central

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

2016-01-01

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

New polymer of lactic-co-glycolic acid-modified polyethylenimine for nucleic acid delivery

PubMed Central

Lü, Jian-Ming; Liang, Zhengdong; Wang, Xiaoxiao; Gu, Jianhua; Yao, Qizhi; Chen, Changyi

2016-01-01

Aim: To develop an improved delivery system for nucleic acids. Materials & methods: We designed, synthesized and characterized a new polymer of lactic-co-glycolic acid-modified polyethylenimine (LGA-PEI). Functions of LGA-PEI polymer were determined. Results: The new LGA-PEI polymer spontaneously formed nanoparticles (NPs) with DNA or RNA, and showed higher DNA or RNA loading efficiency, higher or comparable transfection efficacy, and lower cytotoxicity in several cell types including PANC-1, Jurkat and HEK293 cells, when compared with lipofectamine 2000, branched or linear PEI (25 kDa). In nude mouse models, LGA-PEI showed higher delivery efficiency of plasmid DNA or miRNA mimic into pancreatic and ovarian xenograft tumors. LGA-PEI/DNA NPs showed much lower toxicity than control PEI NPs in mouse models. Conclusion: The new LGA-PEI polymer is a safer and more effective system to deliver DNA or RNA than PEI. PMID:27456396

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

PubMed

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

2012-10-01

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

Pluronic-Functionalized Silica-Lipid Hybrid Microparticles: Improving the Oral Delivery of Poorly Water-Soluble Weak Bases.

PubMed

Rao, Shasha; Richter, Katharina; Nguyen, Tri-Hung; Boyd, Ben J; Porter, Christopher J H; Tan, Angel; Prestidge, Clive A

2015-12-07

A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

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

PubMed Central

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

2014-01-01

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

Controlled release of chlorhexidine digluconate using β-cyclodextrin and microfibrillated cellulose.

PubMed

Lavoine, Nathalie; Tabary, Nicolas; Desloges, Isabelle; Martel, Bernard; Bras, Julien

2014-09-01

This study aims to develop a high-performance delivery system using microfibrillated cellulose (MFC)-coated papers as a controlled release system combined with the well-known drug delivery agent, β-cyclodextrin (βCD). Chlorhexidine digluconate (CHX), an antibacterial molecule, was mixed with a suspension of MFC or a βCD solution or mixed with both the substances, before coating onto a cellulosic substrate. The intermittent diffusion of CHX (i.e., diffusion interrupted by the renewal of the release medium periodically) was conducted in an aqueous medium, and the release mechanism of CHX was elucidated by field emission gun-scanning electron microscopy, SEM, NMR, and Fourier transform infrared analyses. According to the literature, both βCD and MFC are efficient controlled delivery systems. This study indicated that βCD releases CHX more gradually and over a longer period of time compared to MFC, which is mainly due to the ability of βCD to form an inclusion complex with CHX. Furthermore from the release study, a complementary action when the two compounds were combined was deduced. MFC mainly affected the burst effect, while βCD primarily controlled the amount of CHX released over time. In this paper, two different types of controlled release systems are proposed and compared. Depending on the final application, the use of βCD alone would release low amounts of active molecules over time (slow delivery), whereas the combination of β-cyclodextrin and MFC would be more suitable for the release of higher amounts of active molecules over time (rapid delivery). Copyright © 2014 Elsevier B.V. All rights reserved.

Recent advancements in nanoparticle based drug delivery for gastrointestinal disorders.

PubMed

Mittal, Rahul; Patel, Amit P; Jhaveri, Vasanti M; Kay, Sae-In S; Debs, Luca H; Parrish, James M; Pan, Debbie R; Nguyen, Desiree; Mittal, Jeenu; Jayant, Rahul Dev

2018-03-01

The emergent field of nanoparticles has presented a wealth of opportunities for improving the treatment of human diseases. Recent advances have allowed for promising developments in drug delivery, diagnostics, and therapeutics. Modified delivery systems allow improved drug delivery over traditional pH, microbe, or receptor dependent models, while antibody association allows for more advanced imaging modalities. Nanoparticles have potential clinical application in the field of gastroenterology as they offer several advantages compared to the conventional treatment systems including target drug delivery, enhanced treatment efficacy, and reduced side effects. Areas covered: The aim of this review article is to summarize the recent advancements in developing nanoparticle technologies to treat gastrointestinal diseases. We have covered the application of nanoparticles in various gastrointestinal disorders including inflammatory bowel disease and colorectal cancer. We also have discussed how the gut microbiota affects the nanoparticle based drug delivery in the gastrointestinal tract. Expert opinion: Nanoparticles based drug delivery offers a great platform for targeted drug delivery for gastrointestinal disorders. However, it is influenced by the presence of microbiota, drug interaction with nanoparticles, and cytotoxicity of nanoparticles. With the advancements in nanoparticle technology, it may be possible to overcome these barriers leading to efficient drug delivery for gastrointestinal disorders based on nanoparticle platform.

Delivery of chemotherapeutics using spheres made of bioengineered spider silks derived from MaSp1 and MaSp2 proteins.

PubMed

Jastrzebska, Katarzyna; Florczak, Anna; Kucharczyk, Kamil; Lin, Yinnan; Wang, Qin; Mackiewicz, Andrzej; Kaplan, David L; Dams-Kozlowska, Hanna

2018-02-01

Analysis of the properties and chemotherapeutics delivery potential of spheres made of bioengineered spider silks MS1 and MS2. MS1 and MS2 derived from Nephila clavipes dragline silks - MaSp1 and MaSp2, respectively - formed spheres that were compared in terms of physicochemical properties, cytotoxicity and loading/release of chemotherapeutics. MS2 spheres were more dispersed, smaller, of solid core, of higher beta-sheet structure content, and of opposite (negative) charge than MS1 spheres. Preloaded MS2 showed greater applicability for mitoxantrone, while postloaded for etoposide delivery compared with MS1 spheres. However, MS1 spheres were a better choice for doxorubicin delivery than MS2. Bioengineered silks can be tailored to develop a system with optimal drug loading and release properties.

Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

PubMed

Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

2015-02-01

Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

MRI in ocular drug delivery

PubMed Central

Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

2008-01-01

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems.

PubMed

Harari, Colin M; Magagna, Michelle; Bedoya, Mariajose; Lee, Fred T; Lubner, Meghan G; Hinshaw, J Louis; Ziemlewicz, Timothy; Brace, Christopher L

2016-01-01

To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. © RSNA, 2015.

WE-G-BRF-01: Adaptation to Intrafraction Tumor Deformation During Intensity-Modulated Radiotherapy: First Proof-Of-Principle Demonstration

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

Ge, Y; OBrien, R; Shieh, C

2014-06-15

Purpose: Intrafraction tumor deformation limits targeting accuracy in radiotherapy and cannot be adapted to by current motion management techniques. This study simulated intrafractional treatment adaptation to tumor deformations using a dynamic Multi-Leaf Collimator (DMLC) tracking system during Intensity-modulated radiation therapy (IMRT) treatment for the first time. Methods: The DMLC tracking system was developed to adapt to the intrafraction tumor deformation by warping the planned beam aperture guided by the calculated deformation vector field (DVF) obtained from deformable image registration (DIR) at the time of treatment delivery. Seven single phantom deformation images up to 10.4 mm deformation and eight tumor systemmore » phantom deformation images up to 21.5 mm deformation were acquired and used in tracking simulation. The intrafraction adaptation was simulated at the DMLC tracking software platform, which was able to communicate with the image registration software, reshape the instantaneous IMRT field aperture and log the delivered MLC fields.The deformation adaptation accuracy was evaluated by a geometric target coverage metric defined as the sum of the area incorrectly outside and inside the reference aperture. The incremental deformations were arbitrarily determined to take place equally over the delivery interval. The geometric target coverage of delivery with deformation adaptation was compared against the delivery without adaptation. Results: Intrafraction deformation adaptation during dynamic IMRT plan delivery was simulated for single and system deformable phantoms. For the two particular delivery situations, over the treatment course, deformation adaptation improved the target coverage by 89% for single target deformation and 79% for tumor system deformation compared with no-tracking delivery. Conclusion: This work demonstrated the principle of real-time tumor deformation tracking using a DMLC. This is the first step towards the development of an image-guided radiotherapy system to treat deforming tumors in real-time. The authors acknowledge funding support from the Australian NHMRC Australia Fellowship, Cure Cancer Australia Foundation, NHMRC Project Grant APP1042375 and US NIH/NCI R01CA93626.« less

Current HPLC Methods for Assay of Nano Drug Delivery Systems.

PubMed

Tekkeli, Serife Evrim Kepekci; Kiziltas, Mustafa Volkan

2017-01-01

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

Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects.

PubMed

Song, Zhiwang; Lin, Yun; Zhang, Xia; Feng, Chan; Lu, Yonglin; Gao, Yong; Dong, Chunyan

2017-01-01

Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin α v β 3 and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer.

Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects

PubMed Central

Song, Zhiwang; Lin, Yun; Zhang, Xia; Feng, Chan; Lu, Yonglin; Gao, Yong; Dong, Chunyan

2017-01-01

Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin αvβ3 and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer. PMID:28331317

Costs and effects of two public sector delivery channels for long-lasting insecticidal nets in Uganda

PubMed Central

2010-01-01

Background In Uganda, long-lasting insecticidal nets (LLIN) have been predominantly delivered through two public sector channels: targeted campaigns or routine antenatal care (ANC) services. Their combination in a mixed-model strategy is being advocated to quickly increase LLIN coverage and maintain it over time, but there is little evidence on the efficiency of each system. This study evaluated the two delivery channels regarding LLIN retention and use, and estimated the associated costs, to contribute towards the evidence-base on LLIN delivery channels in Uganda. Methods Household surveys were conducted 5-7 months after LLIN distribution, combining questionnaires with visual verification of LLIN presence. Focus groups and interviews were conducted to further investigate determinants of LLIN retention and use. Campaign distribution was evaluated in Jinja and Adjumani while ANC distribution was evaluated only in the latter district. Costs were calculated from the provider perspective through retrospective analysis of expenditure data, and effects were estimated as cost per LLIN delivered and cost per treated-net-year (TNY). These effects were calculated for the total number of LLINs delivered and for those retained and used. Results After 5-7 months, over 90% of LLINs were still owned by recipients, and between 74% (Jinja) and 99% (ANC Adjumani) were being used. Costing results showed that delivery was cheapest for the campaign in Jinja and highest for the ANC channel, with economic delivery cost per net retained and used of USD 1.10 and USD 2.31, respectively. Financial delivery costs for the two channels were similar in the same location, USD 1.04 for campaign or USD 1.07 for ANC delivery in Adjumani, but differed between locations (USD 0.67 for campaign delivery in Jinja). Economic cost for ANC distribution were considerably higher (USD 2.27) compared to campaign costs (USD 1.23) in Adjumani. Conclusions Targeted campaigns and routine ANC services can both achieve high LLIN retention and use among the target population. The comparatively higher economic cost of delivery through ANC facilities was at least partially due to the relatively short time this system had been in existence. Further studies comparing the cost of well-established ANC delivery with LLIN campaigns and other delivery channels are thus encouraged. PMID:20406448

Costs and effects of two public sector delivery channels for long-lasting insecticidal nets in Uganda.

PubMed

Kolaczinski, Jan H; Kolaczinski, Kate; Kyabayinze, Daniel; Strachan, Daniel; Temperley, Matilda; Wijayanandana, Nayantara; Kilian, Albert

2010-04-20

In Uganda, long-lasting insecticidal nets (LLIN) have been predominantly delivered through two public sector channels: targeted campaigns or routine antenatal care (ANC) services. Their combination in a mixed-model strategy is being advocated to quickly increase LLIN coverage and maintain it over time, but there is little evidence on the efficiency of each system. This study evaluated the two delivery channels regarding LLIN retention and use, and estimated the associated costs, to contribute towards the evidence-base on LLIN delivery channels in Uganda. Household surveys were conducted 5-7 months after LLIN distribution, combining questionnaires with visual verification of LLIN presence. Focus groups and interviews were conducted to further investigate determinants of LLIN retention and use. Campaign distribution was evaluated in Jinja and Adjumani while ANC distribution was evaluated only in the latter district. Costs were calculated from the provider perspective through retrospective analysis of expenditure data, and effects were estimated as cost per LLIN delivered and cost per treated-net-year (TNY). These effects were calculated for the total number of LLINs delivered and for those retained and used. After 5-7 months, over 90% of LLINs were still owned by recipients, and between 74% (Jinja) and 99% (ANC Adjumani) were being used. Costing results showed that delivery was cheapest for the campaign in Jinja and highest for the ANC channel, with economic delivery cost per net retained and used of USD 1.10 and USD 2.31, respectively. Financial delivery costs for the two channels were similar in the same location, USD 1.04 for campaign or USD 1.07 for ANC delivery in Adjumani, but differed between locations (USD 0.67 for campaign delivery in Jinja). Economic cost for ANC distribution were considerably higher (USD 2.27) compared to campaign costs (USD 1.23) in Adjumani. Targeted campaigns and routine ANC services can both achieve high LLIN retention and use among the target population. The comparatively higher economic cost of delivery through ANC facilities was at least partially due to the relatively short time this system had been in existence. Further studies comparing the cost of well-established ANC delivery with LLIN campaigns and other delivery channels are thus encouraged.

Intrathecal Drug Delivery and Spinal Cord Stimulation for the Treatment of Cancer Pain.

PubMed

Xing, Fangfang; Yong, R Jason; Kaye, Alan David; Urman, Richard D

2018-02-05

The purpose of the present investigation is to summarize the body and quality of evidence including the most recent studies in support of intrathecal drug delivery systems and spinal cord stimulation for the treatment of cancer-related pain. In the past 3 years, a number of prospective studies have been published supporting intrathecal drug delivery systems for cancer pain. Additional investigation with adjuvants to morphine-based analgesia including dexmedetomidine and ziconotide support drug-induced benefits of patient-controlled intrathecal analgesia. A study has also been recently published regarding cost-savings for intrathecal drug delivery system compared to pharmacologic management, but an analysis in the Ontario, Canada healthcare system projects additional financial costs. Finally, the Polyanalgesic Consensus Committee has updated its recommendations regarding clinical guidelines for intrathecal drug delivery systems to include new information on dosing, trialing, safety, and systemic opioid reduction. There is still a paucity of clinical evidence for spinal cord stimulation in the treatment of cancer pain. There are new intrathecal drugs under investigation including various conopeptides and AYX1. Large, prospective, modern, randomized controlled studies are still needed to support the use of both intrathecal drug delivery systems as well as spinal cord stimulation for cancer pain populations. There are multiple prospective and small randomized controlled studies that highlight a potential promising future for these interventional modalities. Related to the challenge and urgency of cancer pain, the pain practitioner community is moving toward a multimodal approach that includes discussions regarding the role of intrathecal therapies and spinal cord stimulation to the individualized treatment of patients.

In vivo dual-delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy

NASA Astrophysics Data System (ADS)

Araújo, F.; Shrestha, N.; Gomes, M. J.; Herranz-Blanco, B.; Liu, D.; Hirvonen, J. J.; Granja, P. L.; Santos, H. A.; Sarmento, B.

2016-05-01

Oral delivery of proteins is still a challenge in the pharmaceutical field. Nanoparticles are among the most promising carrier systems for the oral delivery of proteins by increasing their oral bioavailability. However, most of the existent data regarding nanosystems for oral protein delivery is from in vitro studies, lacking in vivo experiments to evaluate the efficacy of these systems. Herein, a multifunctional composite system, tailored by droplet microfluidics, was used for dual delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 inhibitor (iDPP4) in vivo. Oral delivery of GLP-1 with nano- or micro-systems has been studied before, but the simultaneous nanodelivery of GLP-1 with iDPP4 is a novel strategy presented here. The type 2 diabetes mellitus (T2DM) rat model, induced through the combined administration of streptozotocin and nicotinamide, a non-obese model of T2DM, was used. The combination of both drugs resulted in an increase in the hypoglycemic effects in a sustained, but prolonged manner, where the iDPP4 improved the therapeutic efficacy of GLP-1. Four hours after the oral administration of the system, blood glucose levels were decreased by 44%, and were constant for another 4 h, representing half of the glucose area under the curve when compared to the control. An enhancement of the plasmatic insulin levels was also observed 6 h after the oral administration of the dual-drug composite system and, although no statistically significant differences existed, the amount of pancreatic insulin was also higher. These are promising results for the oral delivery of GLP-1 to be pursued further in a chronic diabetic model study.

Buccal drug delivery.

PubMed

Smart, John D

2005-05-01

Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.

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

PubMed

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

2011-05-01

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

National health insurance, physician financial incentives, and primary cesarean deliveries in Taiwan.

PubMed

Tsai, Yi-Wen; Hu, Teh-Wei

2002-09-01

Taiwan's National Health Insurance Program (NHI) was implemented on March 1, 1995. This study analyzed the influences of the Case Payment method of reimbursement for inpatient care and of physician financial incentives on a woman's choice for primary cesarean delivery. Logistic regressions were used to analyze 11 788 first-time deliveries in a nonprofit hospital system between March 1, 1994, and February 29, 1996. After implementation of the NHI's Case Payment scheme, the likelihood that a woman would choose primary cesarean delivery increased by four to five times compared with the choice behavior of uninsured individuals prior to NHI (P <.0001). Out-of-pocket payment discourages the selection of primary cesarean delivery. No robust statistics were found relating physician financial incentives to delivery choice.

Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

PubMed

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

2015-01-01

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

Institutional delivery in public and private sectors in South Asia: a comparative analysis of prospective data from four demographic surveillance sites.

PubMed

Das, Sushmita; Alcock, Glyn; Azad, Kishwar; Kuddus, Abdul; Manandhar, Dharma S; Shrestha, Bhim Prasad; Nair, Nirmala; Rath, Shibanand; More, Neena Shah; Saville, Naomi; Houweling, Tanja A J; Osrin, David

2016-09-20

Maternity care in South Asia is available in both public and private sectors. Using data from demographic surveillance sites in Bangladesh, Nepal and rural and urban India, we aimed to compare institutional delivery rates and public-private share. We used records of maternity care collected in socio-economically disadvantaged communities between 2005 and 2011. Institutional delivery was summarized by four potential determinants: household asset index, maternal schooling, maternal age, and parity. We developed logistic regression models for private sector institutional delivery with these as independent covariates. The data described 52 750 deliveries. Institutional delivery proportion varied and there were differences in public-private split. In Bangladesh and urban India, the proportion of deliveries in the private sector increased with wealth, maternal education, and age. The opposite was observed in rural India and Nepal. The proportion of institutional delivery increased with economic status and education. The choice of sector is more complex and provision and perceived quality of public sector services is likely to play a role. Choices for safe maternity are influenced by accessibility, quantity and perceived quality of care. Along with data linkage between private and public sectors, increased regulation should be part of the development of the pluralistic healthcare systems that characterize south Asia.

Naphthalocyanine as a New Photothermal Actuator for Lipid-Based Drug Delivery Systems.

PubMed

Du, Joanne D; Hong, Linda; Tan, Angel; Boyd, Ben J

2018-02-08

One approach to address the substantial global burden of ocular diseases such as aged related macular degeneration is using light-activated drug delivery to obviate the need for highly invasive and frequent, costly intravitreal injections. To enable such systems, new light responsive materials are required. This communication reports the use of silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (SiNC), a small molecule photosensitizer, as a new actuator for triggering light responsive lipid-based drug delivery systems. Small-angle X-ray scattering was used to confirm that the addition of SiNC imparted light sensitivity to the lipid systems, resulting in a complete phase transition within 20 s of near-infrared irradiation. The phase transition was also reversible, suggesting the potential for on-demand drug delivery. When compared to the phase transitions induced using alternative light responsive actuators, gold nanorods and graphene, there were some differences in phase behavior. Namely, the phytantriol with SiNC system transitioned directly to the inverse micellar phase, skipping the intermediate inverse hexagonal structure. The photodynamic properties and efficiency in controlling the release of drug suggest that SiNC-actuated lipid systems have the potential to reduce the burden of repeated intravitreal injections.

Intracoronary and Retrograde Coronary Venous Myocardial Delivery of Adipose-Derived Stem Cells in Swine Infarction Lead to Transient Myocardial Trapping with Predominant Pulmonary Redistribution

PubMed Central

Hong, Soon Jun; Hou, Dongming; Brinton, Todd J.; Johnstone, Brian; Feng, Dongni; Rogers, Pamela; Fearon, William F.; Yock, Paul; March, Keith L.

2012-01-01

Objectives To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous or arterial delivery. Background Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. Methods In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either intracoronary (IC) or retrograde coronary venous (RCV) infusion of 107 111Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hours after cell delivery. Results IC delivery of porcine ASCs to normal myocardium was well-tolerated up to a cumulative dose of 14×106 cells (approximately 0.5×106 cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50×106 ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, while at 10×106 ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hour with IC delivery compared to RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, p=0.037) but this initial difference was not apparent at 24 hours (22.6 ± 5.5% vs. 18.7 ± 8.6%; p= 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hours post-delivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. Conclusions Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. Intracoronary arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise. PMID:22972685

Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend.

PubMed

Kenawy, El-Refaie; Bowlin, Gary L; Mansfield, Kevin; Layman, John; Simpson, David G; Sanders, Elliot H; Wnek, Gary E

2002-05-17

Electrospun fiber mats are explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. The mats were made either from poly(lactic acid) (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two. The fibers were electrospun from chloroform solutions containing a small amount of methanol to solubilize the drug. The release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV-VIS spectroscopy. Release profiles from the electrospun mats were compared to a commercially available drug delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast films of the various formulations.

Pain Experience and Behavior Management in Pediatric Dentistry: A Comparison between Traditional Local Anesthesia and the Wand Computerized Delivery System.

PubMed

Garret-Bernardin, Annelyse; Cantile, Tiziana; D'Antò, Vincenzo; Galanakis, Alexandros; Fauxpoint, Gabriel; Ferrazzano, Gianmaria Fabrizio; De Rosa, Sara; Vallogini, Giulia; Romeo, Umberto; Galeotti, Angela

2017-01-01

Aim. To evaluate the pain experience and behavior during dental injection, using the Wand computerized delivery system versus conventional local anesthesia in children and adolescents. Methods. An observational crossover split mouth study was performed on 67 patients (aged 7 to 15 years), requiring local anesthesia for dental treatments in both sides of the dental arch. Patients received both types of injections in two separate appointments, one with the use of a Computer Delivery System (the Wand STA system) and one with the traditional syringe. The following data were recorded: pain rating; changes in heart rate; level of collaboration; patient satisfaction. The data were analyzed using ANOVA for quantitative outcomes and nonparametric analysis (Kruskal-Wallis) for qualitative parameters. Results. The use of the Wand system determined significantly lower pain ratings and lower increase of heart rate than the traditional syringe. During injection, the number of patients showing a relaxed behavior was higher with the Wand than with the traditional local anesthesia. The patient level of satisfaction was higher with the Wand compared to the conventional local anesthesia. Conclusions. The Wand system may provide a less painful injection when compared to the conventional local anesthesia and it seemed to be better tolerated with respect to a traditional syringe.

Pain Experience and Behavior Management in Pediatric Dentistry: A Comparison between Traditional Local Anesthesia and the Wand Computerized Delivery System

PubMed Central

D'Antò, Vincenzo; Fauxpoint, Gabriel; De Rosa, Sara; Vallogini, Giulia

2017-01-01

Aim. To evaluate the pain experience and behavior during dental injection, using the Wand computerized delivery system versus conventional local anesthesia in children and adolescents. Methods. An observational crossover split mouth study was performed on 67 patients (aged 7 to 15 years), requiring local anesthesia for dental treatments in both sides of the dental arch. Patients received both types of injections in two separate appointments, one with the use of a Computer Delivery System (the Wand STA system) and one with the traditional syringe. The following data were recorded: pain rating; changes in heart rate; level of collaboration; patient satisfaction. The data were analyzed using ANOVA for quantitative outcomes and nonparametric analysis (Kruskal–Wallis) for qualitative parameters. Results. The use of the Wand system determined significantly lower pain ratings and lower increase of heart rate than the traditional syringe. During injection, the number of patients showing a relaxed behavior was higher with the Wand than with the traditional local anesthesia. The patient level of satisfaction was higher with the Wand compared to the conventional local anesthesia. Conclusions. The Wand system may provide a less painful injection when compared to the conventional local anesthesia and it seemed to be better tolerated with respect to a traditional syringe. PMID:28293129

Paclitaxel loaded phospholipid-based gel as a drug delivery system for local treatment of glioma.

PubMed

Chen, Tijia; Gong, Ting; Zhao, Ting; Liu, Xing; Fu, Yao; Zhang, Zhirong; Gong, Tao

2017-08-07

Paclitaxel (PTX) is a chemotherapeutic agent and has been widely used in clinic against human cancer. However, it has limited application in brain tumor treatment due to the poor penetration of blood brain barrier. Local delivery system is a promising carrier of PTX in the treatment of glioma. A biodegradable phospholipid-based gel (PG) system was developed for intratumoral injection and evaluated in brain glioma-bearing mice model. PTX loaded PG was composed of phospholipid, ethanol, medium chain triglyceride, triacetin and PTX. It was prepared by a very simple method. The system was a transparent solution with good fluidity, while turned into a gel after phase-transition when ethanol diffused. Both in vitro dissolution and in vivo imaging study proved the sustained release effect of PG system. In vivo tolerability study showed a better tolerability after mice treated with PTX PG compared with free PTX. The survival time of brain glioma-bearing mice after treatment with PTX PG was significantly prolonged compared with mice treated by free PTX (P<0.05). In conclusion, this study developed a novel PG based local PTX delivery system with simple preparation method, good tolerability and high therapeutic efficacy. It has a great potential to improve the clinical management of glioma. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Recent advancement of gelatin nanoparticles in drug and vaccine delivery.

PubMed

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

2015-11-01

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

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

PubMed

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

2017-04-01

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

Fiber-optic technologies in laser-based therapeutics: threads for a cure.

PubMed

Wang, Zheng; Chocat, Noémie

2010-06-01

In the past decade, novel fiber structures and material compositions have led to the introduction of new diagnostic and therapeutic tools. We review the structure, the material composition and the fabrication processes behind these novel fiber systems. Because of their structural flexibility, their compatibility with endoscopic appliances and their efficiency in laser delivery, these fiber systems have greatly extended the reach of a wide range of surgical lasers in minimally invasive procedures. Much research in novel fiber-optics delivery systems has been focused on the accommodation of higher optical powers and the extension to a broader wavelength range. Until recently, CO2 laser surgery, renowned for its precision and efficiency, was limited to open surgeries by the lack of delivery fibers. Hollow-core photonic bandgap fibers are assessed for their ability to transmit CO2 laser at surgical power level and for their applications in a range of clinical areas. Current fiber-delivery technologies for a number of laser surgery modalities and wavelengths are compared.

Acridine Orange/exosomes increase the delivery and the effectiveness of Acridine Orange in human melanoma cells: A new prototype for theranostics of tumors.

PubMed

Iessi, Elisabetta; Logozzi, Mariantonia; Lugini, Luana; Azzarito, Tommaso; Federici, Cristina; Spugnini, Enrico Pierluigi; Mizzoni, Davide; Di Raimo, Rossella; Angelini, Daniela F; Battistini, Luca; Cecchetti, Serena; Fais, Stefano

2017-12-01

Specifically targeted drug delivery systems with low immunogenicity and toxicity are deemed to increase efficacy of cancer chemotherapy. Acridine Orange (AO) is an acidophilic dye with a strong tumoricidal action following excitation with a light source at 466 nm. However, to date the clinical use of AO is limited by the potential side effects elicited by systemic administration. The endogenous nanocarrier exosomes have been recently introduced as a natural delivery system for therapeutic molecules. In this article, we show the outcome of the administration to human melanoma cells of AO charged Exosomes (Exo-AO), in both monolayer and spheroid models. The results showed an extended drug delivery time of Exo-AO to melanoma cells as compared to the free AO, improving the cytotoxicity of AO. This study shows that Exo-AO have a great potential for a real exploitation as a new theranostic approach against tumors based on AO delivered through the exosomes.

Label-Free Raman Microspectral Analysis for Comparison of Cellular Uptake and Distribution between Non-Targeted and EGFR-Targeted Biodegradable Polymeric Nanoparticles

PubMed Central

Chernenko, Tatyana; Buyukozturk, Fulden; Miljkovic, Milos; Carrier, Rebecca; Diem, Max; Amiji, Mansoor

2013-01-01

Active targeted delivery of nanoparticle-encapsulated agents to tumor cells in vivo is expected to enhance therapeutic effect with significantly less non-specific toxicity. Active targeting is based on surface modification of nanoparticles with ligands that bind with extracellular targets and enhance payload delivery in the cells. In this study, we have used label-free Raman micro-spectral analysis and kinetic modeling to study cellular interactions and intracellular delivery of C6-ceramide using a non-targeted and an epidermal growth factor receptor (EGFR) targeted biodegradable polymeric nano-delivery systems, in EGFR-expressing human ovarian adenocarcinoma (SKOV3) cells. The results show that EGFR peptide-modified nanoparticles were rapidly internalized in SKOV3 cells leading to significant intracellular accumulation as compared to non-specific uptake by the non-targeted nanoparticles. Raman micro-spectral analysis enables visualization and quantification of the carrier system, drug-load, and responses of the biological systems interrogated, without exogenous staining and labeling procedures. PMID:24298430

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

PubMed

Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

2017-01-01

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

The Use of Convection-Enhanced Delivery with Liposomal Toxins in Neurooncology

PubMed Central

Fiandaca, Massimo S.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Liposomes have long been effective delivery vehicles for transport of toxins to peripheral cancers. The combination of convection-enhanced delivery (CED) with liposomal toxins was originally proposed to circumvent the limited delivery of intravascular liposomes to the central nervous system (CNS) due to the blood-brain-barrier (BBB). CED offers markedly improved distribution of infused therapeutics within the CNS compared to direct injection or via drug eluting polymers, both of which depend on diffusion for parenchymal distribution. This review examines the basis for improved delivery of liposomal toxins via CED within the CNS, and discusses preclinical and clinical experience with these therapeutic techniques. How CED and liposomal technologies may influence future neurooncologic treatments are also considered. PMID:22069714

Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution.

PubMed

Hong, Soon Jun; Hou, Dongming; Brinton, Todd J; Johnstone, Brian; Feng, Dongni; Rogers, Pamela; Fearon, William F; Yock, Paul; March, Keith L

2014-01-01

To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery. Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery. IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise. Copyright © 2012 Wiley Periodicals, Inc.

Quality assurance for online adapted treatment plans: benchmarking and delivery monitoring simulation.

PubMed

Li, Taoran; Wu, Qiuwen; Yang, Yun; Rodrigues, Anna; Yin, Fang-Fang; Jackie Wu, Q

2015-01-01

An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system was designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system's performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system's ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.

Versatile types of polysaccharide-based supramolecular polycation/pDNA nanoplexes for gene delivery

NASA Astrophysics Data System (ADS)

Hu, Yang; Zhao, Nana; Yu, Bingran; Liu, Fusheng; Xu, Fu-Jian

2014-06-01

Different polysaccharide-based supramolecular polycations were readily synthesized by assembling multiple β-cyclodextrin-cored star polycations with an adamantane-functionalized dextran via host-guest interaction in the absence or presence of bioreducible linkages. Compared with nanoplexes of the starting star polycation and pDNA, the supramolecular polycation/pDNA nanoplexes exhibited similarly low cytotoxicity, improved cellular internalization and significantly higher gene transfection efficiencies. The incorporation of disulfide linkages imparted the supramolecular polycation/pDNA nanoplexes with the advantage of intracellular bioreducibility, resulting in better gene delivery properties. In addition, the antitumor properties of supramolecular polycation/pDNA nanoplexes were also investigated using a suicide gene therapy system. The present study demonstrates that the proper assembly of cyclodextrin-cored polycations with adamantane-functionalized polysaccharides is an effective strategy for the production of new nanoplex delivery systems.Different polysaccharide-based supramolecular polycations were readily synthesized by assembling multiple β-cyclodextrin-cored star polycations with an adamantane-functionalized dextran via host-guest interaction in the absence or presence of bioreducible linkages. Compared with nanoplexes of the starting star polycation and pDNA, the supramolecular polycation/pDNA nanoplexes exhibited similarly low cytotoxicity, improved cellular internalization and significantly higher gene transfection efficiencies. The incorporation of disulfide linkages imparted the supramolecular polycation/pDNA nanoplexes with the advantage of intracellular bioreducibility, resulting in better gene delivery properties. In addition, the antitumor properties of supramolecular polycation/pDNA nanoplexes were also investigated using a suicide gene therapy system. The present study demonstrates that the proper assembly of cyclodextrin-cored polycations with adamantane-functionalized polysaccharides is an effective strategy for the production of new nanoplex delivery systems. Electronic supplementary information (ESI) available: 1H NMR assay and synthetic route of Dex-Ad and Dex-SS-Ad. See DOI: 10.1039/c4nr01590h

Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye.

PubMed

Zhou, Chengxin; Robert, Marie-Claude; Kapoulea, Vassiliki; Lei, Fengyang; Stagner, Anna M; Jakobiec, Frederick A; Dohlman, Claes H; Paschalis, Eleftherios I

2017-01-01

Tumor necrosis factor (TNF)-α is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-α inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-α inhibitors carries risk of significant complications, whereas topical eye-drop delivery is hindered by poor ocular bioavailability and the need for patient adherence. This study investigates the efficacy of subconjunctival delivery of TNF-α antibodies using a polymer-based drug delivery system (DDS). The drug delivery system was prepared using porous polydimethylsiloxane/polyvinyl alcohol composite fabrication and loaded with 85 μg of infliximab. Six Dutch-belted pigmented rabbits received ocular alkali burn with NaOH. Immediately after the burn, subconjunctival implantation of anti-TNF-α DDS was performed in three rabbits while another three received sham DDS (without antibody). Rabbits were followed with photography for 3 months. After 3 months, the device was found to be well tolerated by the host and the eyes exhibited less corneal damage as compared to eyes implanted with a sham DDS without drug. The low dose treatment suppressed CD45 and TNF-α expression in the burned cornea and inhibited retinal ganglion cell apoptosis and optic nerve degeneration, as compared to the sham DDS treated eyes. Immunolocalization revealed drug penetration in the conjunctiva, cornea, iris, and choroid, with residual infliximab in the DDS 3 months after implantation. This reduced-risk biologic DDS improves corneal wound healing and provides retinal neuroprotection, and may be applicable not only to alkali burns but also to other inflammatory surgical procedures such as penetrating keratoplasty and keratoprosthesis implantation.

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.

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

Chen, Q; Read, P

Purpose: Multiple error pathways can lead to delivery errors during the treatment course that cannot be caught with pre-treatment QA. While in vivo solutions are being developed for linacs, no such solution exists for tomotherapy. The purpose of this study is to develop a near real-time system for tomotherapy that can monitor the delivery and dose accumulation process during the treatment-delivery, which enable the user to assess the impact of delivery variations and/or errors and to interrupt the treatment if necessary. Methods: A program running on a tomotherapy planning station fetches the raw DAS data during treatment. Exit detector datamore » is extracted as well as output, gantry angle, and other machine parameters. For each sample, the MLC open-close state is determined. The delivered plan is compared with the original plan via a Monte Carlo dose engine which transports fluence deviations from a pre-treatment Monte Carlo run. A report containing the difference in fluence, dose and DVH statistics is created in html format. This process is repeated until the treatment is completed. Results: Since we only need to compute the dose for the difference in fluence for a few projections each time, dose with 2% statistical uncertainty can be computed in less than 1 second on a 4-core cpu. However, the current bottleneck in this near real-time system is the repeated fetching and processing the growing DAS data file throughout the delivery. The frame rate drops from 10Hz at the beginning of treatment to 5Hz after 3 minutes and to 2Hz after 10 minutes. Conclusion: A during-treatment delivery monitor system has been built to monitor tomotherapy treatments. The system improves patient safety by allowing operators to assess the delivery variations and errors during treatment delivery and adopt appropriate actions.« less

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

PubMed

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

PubMed Central

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel

2016-01-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929

Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo

PubMed Central

Klippstein, Rebecca; Wang, Julie Tzu-Wen; El-Gogary, Riham I; Bai, Jie; Mustafa, Falisa; Rubio, Noelia; Bansal, Sukhvinder; Al-Jamal, Wafa T; Al-Jamal, Khuloud T

2015-01-01

Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil-cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non-PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer. PMID:26140363

Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

NASA Astrophysics Data System (ADS)

Shalviri, Alireza

The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in controlled delivery applications of larger molecular size compounds. The starch based hydrogels, polymers and nanoparticles developed in this work have shown great potentials for controlled drug delivery and biomedical imaging applications.

Enhancing topical analgesic administration: review and prospect for transdermal and transbuccal drug delivery systems.

PubMed

Sanz, Roser; Calpena, Ana C; Mallandrich, Mireia; Clares, Beatriz

2015-01-01

Topical administration is an appealing method for drug delivery due to its non-invasiveness, self-controlled application, avoidance of first-pass metabolism in the liver and reduction of systemic side effects compared to other conventional routes such as oral and parenteral. However, topical administration must overcome the permeable barriers that skin and mucosa represent for the drug to achieve its desired therapeutic effect. Penetration of drugs through human skin is mainly impaired by the stratum corneum- the uppermost keratinized skin layer. In contrast, the stratified squamous epithelium (a nonkeratinized tissue) represents the major physical barrier for transbuccal drug administration in humans. Different technologies have been studied to enhance the bioavailability or local effects of drugs administered through skin and buccal mucosa. Those technologies involve the use of physical or chemical enhancers and new dosage forms such as vesicles, cyclodextrins, nanoparticles and other complex systems. Combinations of these technologies may further increase drug delivery in some cases. As analgesia is one of the main therapeutic effects sought through topical administration, this paper focuses on the review of drug delivery systems to improve the topical and transdermal/transbuccal drug delivery of substances with known analgesic action. A discussion of their possibilities and limitations is also included.

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

PubMed Central

Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

2017-01-01

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors.

PubMed

Tosi, Umberto; Marnell, Christopher S; Chang, Raymond; Cho, William C; Ting, Richard; Maachani, Uday B; Souweidane, Mark M

2017-02-08

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a "wait-and-see" approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Noninvasive delivery systems for peptides and proteins in osteoporosis therapy: a retroperspective.

PubMed

Hoyer, Herbert; Perera, Glen; Bernkop-Schnürch, Andreas

2010-01-01

The aim of this review is to provide the reader general and inspiring prospects in various attempts to make noninvasive delivery systems of calcitonin and teriparatide feasible and as convenient as possible. Calcitonin and teriparatide play an important role in both calcium homeostasis and bone remodelling. Currently calcitonin is available as a subcutaneous injection and as a nasal spray whereas teriparatide is administered subcutaneously. In the past few years, an increasing number of articles about drug delivery systems for calcitonin and teriparatide have been published. These delivery systems have been developed to overcome the inherent barriers for the uptake across the diverse membranes on the various routes for protein and peptide delivery. Co-administration of permeation enhancers, mucoadhesive agents, viscosity modifying agents, multifunctional polymers, protease inhibitors as well as encapsulation and chemical modification are utilized in order to improve calcitonin and teriparatide absorption after oral, nasal, pulmonal, or buccal administration. The majority of research groups have been working on the development of formulations based on the encapsulation of molecules in biodegradable and biocompatible polymeric nanoparticles. However these observations are based on data obtained under different experimental conditions. Hence, it is difficult to compare the obtained results in order to draw general conclusions about the most promising characteristics required for oral and nasal formulations for these peptides.

Formulation and evaluation of an in situ gel forming system for controlled delivery of triptorelin acetate.

PubMed

Abashzadeh, Sh; Dinarvand, R; Sharifzadeh, M; Hassanzadeh, G; Amini, M; Atyabi, F

2011-11-20

The novel physical hydrogels composed of chitosan or its water soluble derivatives such as carboxymethyl chitosan (CMCh) and sodium carboxymethyl chitosan (NaCMCh) and opened ring polyvinyl pyrrolidone (OP-PVP) were used as a controlled delivery system for triptorelin acetate, a luteinizing-releasing hormone agonist. The in situ gel forming system designed according to physical interactions such as chains entanglements and hydrophilic attractions especially h-bonds of chitosan and/or NaCMCh and OR-PVP. In order to increase in situ gel forming rate the chitosan microspheres prepared through spray drying technique. The chitosan or NaCMCh/OR-PVP blends prepared at different ratios (0.05, 0.10, 0.12, 0.16, 0.20 and 0.24) and suspended in sesame oil as non-aqueous vehicle at different solid content (10-30%). The suitable ratio of polymers with faster in situ gel forming rate was selected for in vivo studies. The gel formation and drug release from the system was evaluated both in vitro and in vivo. In vitro and in vivo results were compared with Diphereline SR 3.75mg, a commercially available controlled delivery system of triptorelin. In vitro release studies showed a sustained release profile for about 192h with first order kinetics. In vivo studies on male rats by determination of serum testosterone were confirmed the acceptable performance of in situ gel forming system compared with Diphereline SR in decreasing the serum testosterone level for 35days, demonstrating the potential of the novel in situ gel forming system for controlled delivery of peptides. Copyright © 2011 Elsevier B.V. All rights reserved.

The Rural Health Care Delivery System in the Dingxian Experiment: A Case Study of Educational Transfer in Republican China.

ERIC Educational Resources Information Center

Lee, Wai-man; Lo, L. Nai-kwai

1988-01-01

Discusses dependency theory in comparative education studies. Examines U.S. educational transfer to China during the Republican period as it functioned through the public health delivery model of the Dingxian Experiment. Notes that resistance to dependency in this case could serve as a model for avoiding the technological misfitting of programs.…

Optimization of naltrexone diclofenac codrugs for sustained drug delivery across microneedle-treated skin.

PubMed

Ghosh, Priyanka; Lee, DoMin; Kim, Kyung Bo; Stinchcomb, Audra L

2014-01-01

The purpose of this work was to optimize the structure of codrugs for extended delivery across microneedle treated skin. Naltrexone, the model compound was linked with diclofenac, a nonspecific cyclooxygenase inhibitor to enhance the pore lifetime following microneedle treatment and develop a 7 day transdermal system for naltrexone. Four different codrugs of naltrexone and diclofenac were compared in terms of stability and solubility. Transdermal flux, permeability and skin concentration of both parent drugs and codrugs were quantified to form a structure permeability relationship. The results indicated that all codrugs bioconverted in the skin. The degree of conversion was dependent on the structure, phenol linked codrugs were less stable compared to the secondary alcohol linked structures. The flux of naltrexone across microneedle treated skin and the skin concentration of diclofenac were higher for the phenol linked codrugs. The polyethylene glycol link enhanced solubility of the codrugs, which translated into flux enhancement. The current studies indicated that formulation stability of codrugs and the flux of naltrexone can be enhanced via structure design optimization. The polyethylene glycol linked naltrexone diclofenac codrug is better suited for a 7 day drug delivery system both in terms of stability and drug delivery.

Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems

PubMed Central

Harari, Colin M.; Magagna, Michelle; Bedoya, Mariajose; Lee, Fred T.; Lubner, Meghan G.; Hinshaw, J. Louis; Ziemlewicz, Timothy

2016-01-01

Purpose To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. Materials and Methods All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. Results On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. Conclusion The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. © RSNA, 2015 PMID:26133361

'Genipin' - the natural water soluble cross-linking agent and its importance in the modified drug delivery systems: an overview.

PubMed

Manickam, Balamurugan; Sreedharan, Rajesh; Elumalai, Manogaran

2014-01-01

One of the popular approaches in controlling drug delivery from the polymeric carriers is suitably achieved by the inclusion of crosslinking agents into the formulations at different concentrations. Nevertheless, addition of the chemical crosslinkers such as glutaraldehyde, formaldehyde etc, used in the drug delivery systems causes very serious cytotoxic reactions. These chemical crosslinking agents did not offer any significant advantageous effects when compared to the natural crosslinking agents for instance genipin, which is quite less toxic, biocompatible and offers very stable crosslinked products. Based on the earlier reports the safety of this particular natural crosslinker is very well established, since it has been widely used as a Chinese traditional medicine for long-time, isolated from fruits of the plant Gardenia jasminoides Ellis. This concise article largely portrayed the value of this unique natural crosslinker, utilized in controlling the drug delivery from the various formulations.

A high-density lipoprotein-mediated drug delivery system.

PubMed

Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

2016-11-15

High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain.

PubMed

Upadhyay, Urvashi M; Tyler, Betty; Patta, Yoda; Wicks, Robert; Spencer, Kevin; Scott, Alexander; Masi, Byron; Hwang, Lee; Grossman, Rachel; Cima, Michael; Brem, Henry; Langer, Robert

2014-11-11

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.

Photo-synthesis of protein-based nanoparticles and the application in drug delivery

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

Xie, Jinbing; Wang, Hongyang; Cao, Yi

Recently, protein-based nanoparticles as drug delivery systems have attracted great interests due to the excellent behavior of high biocompatibility and biodegradability, and low toxicity. However, the synthesis techniques are generally costly, chemical reagents introduced, and especially present difficulties in producing homogeneous monodispersed nanoparticles. Here, we introduce a novel physical method to synthesize protein nanoparticles which can be accomplished under physiological condition only through ultraviolet (UV) illumination. By accurately adjusting the intensity and illumination time of UV light, disulfide bonds in proteins can be selectively reduced and the subsequent self-assembly process can be well controlled. Importantly, the co-assembly can also bemore » dominated when the proteins mixed with either anti-cancer drugs, siRNA, or active targeting molecules. Both in vitro and in vivo experiments indicate that our synthesized protein–drug nanoparticles (drug-loading content and encapsulation efficiency being ca. 8.2% and 70%, respectively) not only possess the capability of traditional drug delivery systems (DDS), but also have a greater drug delivery efficiency to the tumor sites and a better inhibition of tumor growth (only 35% of volume comparing to the natural growing state), indicating it being a novel drug delivery system in tumor therapy.« less

Bioavailability enhancers of herbal origin: An overview

PubMed Central

Kesarwani, Kritika; Gupta, Rajiv

2013-01-01

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds. PMID:23620848

Towards soft robotic devices for site-specific drug delivery.

PubMed

Alici, Gursel

2015-01-01

Considerable research efforts have recently been dedicated to the establishment of various drug delivery systems (DDS) that are mechanical/physical, chemical and biological/molecular DDS. In this paper, we report on the recent advances in site-specific drug delivery (site-specific, controlled, targeted or smart drug delivery are terms used interchangeably in the literature, to mean to transport a drug or a therapeutic agent to a desired location within the body and release it as desired with negligibly small toxicity and side effect compared to classical drug administration means such as peroral, parenteral, transmucosal, topical and inhalation) based on mechanical/physical systems consisting of implantable and robotic drug delivery systems. While we specifically focus on the robotic or autonomous DDS, which can be reprogrammable and provide multiple doses of a drug at a required time and rate, we briefly cover the implanted DDS, which are well-developed relative to the robotic DDS, to highlight the design and performance requirements, and investigate issues associated with the robotic DDS. Critical research issues associated with both DDSs are presented to describe the research challenges ahead of us in order to establish soft robotic devices for clinical and biomedical applications.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats.

PubMed

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm.

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats

PubMed Central

Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

2016-01-01

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm. PMID:27336852

An in vitro evaluation of the pressure generated during programmed intermittent epidural bolus injection at varying infusion delivery speeds.

PubMed

Klumpner, Thomas T; Lange, Elizabeth M S; Ahmed, Heena S; Fitzgerald, Paul C; Wong, Cynthia A; Toledo, Paloma

2016-11-01

Programmed intermittent bolus injection of epidural anesthetic solution results in decreased anesthetic consumption and better patient satisfaction compared with continuous infusion, presumably by better spread of the anesthetic solution in the epidural space. It is not known whether the delivery speed of the bolus injection influences analgesia outcomes. The objective of this in vitro study was to determine the pressure generated by a programmed intermittent bolus pump at 4 infusion delivery speeds through open-ended, single-orifice and closed-end, multiorifice epidural catheters. In vitro observational study. Not applicable. Not applicable. A CADD-Solis Pain Management System v3.0 with Programmed Intermittent Bolus Model 2110 was connected via a 3-way adapter to an epidural catheter and a digital pressure transducer. Pressures generated by delivery speeds of 100, 175, 300, and 400 mL/h of saline solution were tested with 4 epidural catheters (2 single orifice and 2 multiorifice). These runs were replicated on 5 pumps. Analysis of variance was used to compare the mean peak pressures of each delivery speed within each catheter group (single orifice and multiorifice). Thirty runs at each delivery speed were performed with each type of catheter for a total of 240 experimental runs. Peak pressure increased with increasing delivery speeds in both catheter groups (P<.001). Peak pressures were higher with the multiorifice catheter compared with the single-orifice catheter at all delivery speeds (P<.001, for all). Using a pump designed for programmed intermittent infusion boluses, the delivery speed of saline solution through epidural catheters was directly related to the peak pressures. Future work should evaluate whether differences in the delivery speed of anesthetic solution into the epidural space correlate with differences in the duration and quality of analgesia during programmed intermittent epidural bolus delivery. Copyright © 2016 Elsevier Inc. All rights reserved.

Optical multicast system for data center networks.

PubMed

Samadi, Payman; Gupta, Varun; Xu, Junjie; Wang, Howard; Zussman, Gil; Bergman, Keren

2015-08-24

We present the design and experimental evaluation of an Optical Multicast System for Data Center Networks, a hardware-software system architecture that uniquely integrates passive optical splitters in a hybrid network architecture for faster and simpler delivery of multicast traffic flows. An application-driven control plane manages the integrated optical and electronic switched traffic routing in the data plane layer. The control plane includes a resource allocation algorithm to optimally assign optical splitters to the flows. The hardware architecture is built on a hybrid network with both Electronic Packet Switching (EPS) and Optical Circuit Switching (OCS) networks to aggregate Top-of-Rack switches. The OCS is also the connectivity substrate of splitters to the optical network. The optical multicast system implementation requires only commodity optical components. We built a prototype and developed a simulation environment to evaluate the performance of the system for bulk multicasting. Experimental and numerical results show simultaneous delivery of multicast flows to all receivers with steady throughput. Compared to IP multicast that is the electronic counterpart, optical multicast performs with less protocol complexity and reduced energy consumption. Compared to peer-to-peer multicast methods, it achieves at minimum an order of magnitude higher throughput for flows under 250 MB with significantly less connection overheads. Furthermore, for delivering 20 TB of data containing only 15% multicast flows, it reduces the total delivery energy consumption by 50% and improves latency by 55% compared to a data center with a sole non-blocking EPS network.

High efficient anti-cancer drug delivery systems using tea polyphenols reduced and functionalized graphene oxide.

PubMed

Wang, Xiaoqian; Hao, Liying; Zhang, Chaoliang; Chen, Jiao; Zhang, Ping

2017-03-01

Targeted drug delivery is urgently needed for cancer therapy, and green synthesis is important for the biomedical use of drug delivery systems in the human body. In this work, we report two targeted delivery systems for anticancer drugs based on tea polyphenol functionalized and reduced graphene oxide (TPGs). The obtained TPGs demonstrated an efficient doxorubicin loading capacity as high as 3.430 × 10 6  mg g -1 and 3.932 × 10 4  mg g -1 , and exhibited pH-triggered release. Furthermore, the kinetic models, adsorption isotherms, and possible loading mechanisms were investigated in details. Compared to TPG1 and free doxorubicin, TPG2 is biocompatible to normal cells even at high concentrations and promotes tumor cells death by delivering the doxorubicin mainly to the nuclei. These results were confirmed using cell viability tests and confocal laser microscopy. Moreover, apoptosis tests showed that the mechanism of cancer cell death induced by TPG1 and TPG2 might follow the similar mechanisms. Taken together, these results demonstrate that TPGs provide a multifunctional drug delivery system with a greater loading capacity and pH-sensitive drug release for enhanced cancer therapy. The high drug payload capability and enhanced antitumor efficacy demonstrate that we developed systems are promising for various biomedical applications and cancer therapy.

Solid lipid nanoparticles mediate non-viral delivery of plasmid DNA to dendritic cells

NASA Astrophysics Data System (ADS)

Penumarthi, Alekhya; Parashar, Deepti; Abraham, Amanda N.; Dekiwadia, Chaitali; Macreadie, Ian; Shukla, Ravi; Smooker, Peter M.

2017-06-01

There is an increasing demand for novel DNA vaccine delivery systems, mainly for the non-viral type as they are considered relatively safe. Therefore, solid lipid nanoparticles (SLNs) were investigated for their suitability as a non-viral DNA vaccine delivery system. SLNs were synthesised by a modified solvent-emulsification method in order to study their potential to conjugate with plasmid DNA and deliver them in vitro to dendritic cells using eGFP as the reporter plasmid. The DNA-SLN complexes were characterised by electron microscopy, gel retardation assays and dynamic light scattering. The cytotoxicity assay data supported their biocompatibility and was used to estimate safe threshold concentration resulting in high transfection rate. The transfection efficiency of these complexes in a dendritic cell line was shown to increase significantly compared to plasmid alone, and was comparable to that mediated by lipofectamine. Transmission electron microscopy studies delineated the pathway of cellular uptake. Endosomal escape was observed supporting the mechanism of transfection.

Self-Assembled Cubic Liquid Crystalline Nanoparticles for Transdermal Delivery of Paeonol

PubMed Central

Li, Jian-Chun; Zhu, Na; Zhu, Jin-Xiu; Zhang, Wen-Jing; Zhang, Hong-Min; Wang, Qing-Qing; Wu, Xiao-Xiang; Wang, Xiu; Zhang, Jin; Hao, Ji-Fu

2015-01-01

Background The aim of this study was to optimize the preparation method for self-assembled glyceryl monoolein-based cubosomes containing paeonol and to characterize the properties of this transdermal delivery system to improve the drug penetration ability in the skin. Material/Methods In this study, the cubic liquid crystalline nanoparticles loaded with paeonol were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel by high-pressure homogenization. We evaluated the Zeta potential of these promising skin-targeting drug-delivery systems using the Malvern Zeta sizer examination, and various microscopies and differential scanning calorimetry were also used for property investigation. Stimulating studies were evaluated based on the skin irritation reaction score standard and the skin stimulus intensity evaluation standard for paeonol cubosomes when compared with commercial paeonol ointment. In vitro tests were performed on excised rat skins in an improved Franz diffusion apparatus. The amount of paeonol over time in the in vitro penetration and retention experiments both was determined quantitatively by HPLC. Results Stimulating studies were compared with the commercial ointment which indicated that the paeonol cubic liquid crystalline nanoparticles could reduce the irritation in the skin stimulating test. Thus, based on the attractive characteristics of the cubic crystal system of paeonol, we will further exploit the cosmetic features in the future studies. Conclusions The transdermal delivery system of paeonol with low-irritation based on the self-assembled cubic liquid crystalline nanoparticles prepared in this study might be a promising system of good tropical preparation for skin application. PMID:26517086

Utilization of solid lipid nanoparticles for enhanced delivery of curcumin in cocultures of HT29-MTX and Caco-2 cells.

PubMed

Guri, Anilda; Gülseren, Ibrahim; Corredig, Milena

2013-09-01

Solid lipid nanoparticles (SLN) have shown potential for encapsulation, protection and delivery of lipophilic functional components. In this study, we have investigated the capabilities of SLN to deliver a hydrophobic polyphenol compound, curcumin, in a coculture system of absorptive Caco-2 and mucus secreting HT29-MTX cells. The cells were grown on transport filters to mimic the human intestinal epithelium. Because of the hydrophobic nature of curcumin, its delivery to the basolateral compartment is expected to take place via a paracellular route. The changes in curcumin concentration in various compartments (i.e., apical, basolateral, mucus, and cell lysates) were evaluated using fluorescence spectroscopy. Two SLN systems were prepared with different emulsifying agents. The encapsulation of curcumin in SLN caused enhanced delivery compared to unencapsulated curcumin. In addition, SLN showed enhanced delivery compared to emulsion droplets containing liquid soy oil. The SLN were retained on the apical mucosal layer to a greater extent than emulsion droplets. The presence of SLN did not affect the integrity of the cellular junctions, as indicated by the TEER values, and the route of transport of the solid particles was simple diffusion, with permeability rates of about 7 × 10(-6) cm s(-1). Approximately 1% of total curcumin was delivered to the basolateral compartment, suggesting that most of the curcumin was absorbed and metabolized by the cell.

Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

NASA Astrophysics Data System (ADS)

Durán-Lobato, Matilde; Martín-Banderas, Lucía; Gonçalves, Lídia M. D.; Fernández-Arévalo, Mercedes; Almeida, Antonio J.

2015-02-01

The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.

Quality assurance for online adapted treatment plans: Benchmarking and delivery monitoring simulation

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

Li, Taoran, E-mail: taoran.li.duke@gmail.com; Wu, Qiuwen; Yang, Yun

Purpose: An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. Methods: The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system wasmore » designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system’s performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Results: Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system’s ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. Conclusions: The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.« less

Australian Education in Cross-National Perspective: A Comparative Analysis with France.

ERIC Educational Resources Information Center

Teese, Richard

1988-01-01

Compares Australian and French postcompulsory education delivery systems, focusing on participation by young people within respective frameworks. Examines substantial difference between teenagers' educational participation in two countries, reflecting basically different organizational frameworks. Examines educational stratification, suggesting…

Incorporation of Levodopa into Biopolymer Coatings Based on Carboxylated Carbon Nanotubes for pH-Dependent Sustained Release Drug Delivery.

PubMed

Tan, Julia Meihua; Saifullah, Bullo; Kura, Aminu Umar; Fakurazi, Sharida; Hussein, Mohd Zobir

2018-05-31

Four drug delivery systems were formulated by non-covalent functionalization of carboxylated single walled carbon nanotubes using biocompatible polymers as coating agent (i.e., Tween 20, Tween 80, chitosan or polyethylene glycol) for the delivery of levodopa, a drug used in Parkinson's disease. The chemical interaction between the coating agent and carbon nanotubes-levodopa conjugate was confirmed by Fourier transform infrared (FTIR) and Raman studies. The drug release profiles were revealed to be dependent upon the type of applied coating material and this could be further adjusted to a desired rate to meet different biomedical conditions. In vitro drug release experiments measured using UV-Vis spectrometry demonstrated that the coated conjugates yielded a more prolonged and sustained release pattern compared to the uncoated conjugate. Cytotoxicity of the formulated conjugates was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using normal mouse embryonic fibroblast 3T3 cell line. Compared to the non-coated conjugate, the MTT data indicated that the coating procedure improved the biocompatibility of all systems by 34⁻41% when the concentration used exceeded 100 μg/mL. In conclusion, the comprehensive results of this study suggest that carbon nanotubes-based drug carrier coated with a suitable biomaterial may possibly be a potential nanoparticle system that could facilitate drug delivery to the brain with tunable physicochemical properties.

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

PubMed

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

2008-11-15

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

PEGylation of polypropylenimine dendrimers: effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells.

PubMed

Somani, Sukrut; Laskar, Partha; Altwaijry, Najla; Kewcharoenvong, Paphitchaya; Irving, Craig; Robb, Gillian; Pickard, Benjamin S; Dufès, Christine

2018-06-20

Diaminobutyric polypropylenimine (DAB) dendrimers have been shown to be highly efficient non-viral gene delivery systems for cancer therapy. However, their cytotoxicity currently limits their applications. To overcome this issue, PEGylation of DAB dendrimer, using various PEG molecular weights and dendrimer generations, has been attempted to decrease the cytotoxicity and enhance the DNA condensation, size and zeta potential, cellular uptake and transfection efficacy of these dendriplexes. Among all the PEGylated dendrimers synthesized, generation 3- and generation 4-DAB conjugated to low molecular weight PEG (2 kDa) at a dendrimer: DNA ratio of 20:1 and 10:1 resulted in an increase in gene expression on almost all tested cancer cells lines (by up to 3.2-fold compared to unmodified dendrimer in A431 cells). The highest level of β-galactosidase gene expression (10.07 × 10 -3  ± 0.09 × 10 -3  U/mL) was obtained following treatment of B16F10-Luc cells with G4-dendrimer PEGylated with PEG2K at a dendrimer: DNA ratio of 20:1. These delivery systems significantly decreased cytotoxicity on B16F10-Luc cells, by more than 3.4-fold compared to unmodified dendrimer. PEGylated generations 3- and 4-DAB dendrimers are therefore promising gene delivery systems for cancer therapy, combining low cytotoxicity and high transfection efficacy.

Nanotechnological advances for cutaneous release of tretinoin: an approach to minimize side effects and improve therapeutic efficacy.

PubMed

Raminelli, Ana Claudia Pompeu; Romero, Valeria; Semreen, Mohammad H; Leonardi, Gislaine Ricci

2018-03-12

The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. Herein we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A fluorescence-based imaging approach to pharmacokinetic analysis of intracochlear drug delivery.

PubMed

Ayoob, Andrew M; Peppi, Marcello; Tandon, Vishal; Langer, Robert; Borenstein, Jeffrey T

2018-04-05

Advances in microelectromechanical systems (MEMS) technologies are enhancing the development of intracochlear delivery devices for the treatment of hearing loss with emerging pharmacological therapies. Direct intracochlear delivery addresses the limitations of systemic and intratympanic delivery. However, optimization of delivery parameters for these devices requires pharmacokinetic assessment of the spatiotemporal drug distribution inside the cochlea. Robust methods of measuring drug concentration in the perilymph have been developed, but lack spatial resolution along the tonotopic axis or require complex physiological measurements. Here we describe an approach for quantifying distribution of fluorescent drug-surrogate probe along the cochlea's sensory epithelium with high spatial resolution enabled by confocal fluorescence imaging. Fluorescence from FM 1-43 FX, a fixable endocytosis marker, was quantified using confocal fluorescence imaging of whole mount sections of the organ of Corti from cochleae resected and fixed at several time points after intracochlear delivery. Intracochlear delivery of FM 1-43 FX near the base of the cochlea produces a base-apex gradient of fluorescence in the row of inner hair cells after 1 h post-delivery that is consistent with diffusion-limited transport along the scala tympani. By 3 h post-delivery there is approximately an order of magnitude decrease in peak average fluorescence intensity, suggesting FM 1-43 FX clearance from both the perilymph and inner hair cells. The increase in fluorescence intensity at 72 h post-delivery compared to 3 h post-delivery may implicate a potential radial transport pathway into the scala media. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhancement of human oral bioavailability and in vitro antitumor activity of rosuvastatin via spray dried self-nanoemulsifying drug delivery system.

PubMed

Kamel, Amany O; Mahmoud, Azza A

2013-01-01

The purpose of this study was to develop spray dried self-nanoemulsifying drug delivery system (SNEDDS) tablets of rosuvastatin using mannitol as a carrier. SNEDDS were prepared using Capryol 90, poloxamer 407 and Transcutol P or triacetin as oil, surfactant and cosurfactants, respectively. The prepared systems were characterized and their cytotoxicity was evaluated using Caco-2 cell lines. A comparative bioavailability study was performed in human volunteers relative to the conventional commercial product. Results showed better self-nanoemulsifying ability of systems containing triacetin compared to Transcutol P. SNEDDS formed uni-modal nanoemulsion droplet size distributions with droplet size less than 50 nm and polydispersity index values ranging from 0.127 to 0.275. The solubilizing capacity of rosuvastatin was affected by both surfactant and cosurfactant concentrations. Upon spray drying, systems prepared using Transcutol P tended to be soft and tacky and were sticking to the walls of the dryer. The redispersion of rosuvastatin from solid SNEDDS was very fast (100% within 5 minutes). Optimized SNEDDS prepared with triacetin were safe with no cytotoxic effect on Caco-2 cells. The anticancer effect of rosuvastatin was enhanced when incorporated in SNEDDS (IC50 value decreased from 4 to 3 microg/ml) due to the increase in penetration of SNEDDS inside the cells. The relative bioavailability for SNEDDS tablets compared to the commercial tablets was 167%. The effective solubilization, penetration and enhancement in bioavailability of SNEDDS tablets proves their potential as a safe, and effective drug delivery system for poorly-soluble drugs.

Non-ototoxic local delivery of bisphosphonate to the mammalian cochlea

PubMed Central

Kang, Woo Seok; Sun, Shuting; Nguyen, Kim; Kashemirov, Boris; McKenna, Charles E.; Hacking, S. Adam; Quesnel, Alicia M.; Sewell, William F.; McKenna, Michael J.; Jung, David H.

2015-01-01

Hypothesis Local delivery of bisphosphonates results in superior localization of these compounds for the treatment of cochlear otosclerosis, without ototoxicity. Background Otosclerosis is a common disorder of abnormal bone remodeling within the human otic capsule. It is a frequent cause of conductive hearing loss from stapes fixation. Large lesions that penetrate the cochlear endosteum and injure the spiral ligament result in sensorineural hearing loss. Nitrogen-containing bisphosphonates (e.g., zoledronate) are potent inhibitors of bone remodeling with proven efficacy in the treatment of metabolic bone diseases, including otosclerosis. Local delivery to the cochlea may allow for improved drug targeting, higher local concentrations, and the avoidance of systemic complications. In this study, we utilize a fluorescently labeled bisphosphonate compound (6-FAM-ZOL) to determine drug localization and concentration within the otic capsule. Various methods for delivery are compared. Ototoxicity is evaluated by ABR and DPOAEs. Methods 6-FAM-ZOL was administered to guinea pigs via intraperitoneal injection, placement of alginate beads onto the round window membrane (RWM), or microfluidic pump infusion via a cochleostomy. Hearing was evaluated. Specimens were embedded into resin blocks, ground to a mid-modiolar section, and quantitatively imaged using fluorescence microscopy. Results There was a dose-dependent increase in fluorescent signal following systemic 6-FAM-ZOL treatment. Local delivery via the RWM or a cochleostomy increased delivery efficiency. No significant ototoxicity was observed following either systemic or local 6-FAM-ZOL delivery. Conclusions These findings establish important pre-clinical parameters for the treatment of cochlear otosclerosis in humans. PMID:25996080

Delivery of cyclodextrin polymers to bacterial biofilms - An exploratory study using rhodamine labelled cyclodextrins and multiphoton microscopy.

PubMed

Thomsen, Hanna; Benkovics, Gábor; Fenyvesi, Éva; Farewell, Anne; Malanga, Milo; Ericson, Marica B

2017-10-15

Cyclodextrin (CD) polymers are interesting nanoparticulate systems for pharmaceutical delivery; however, knowledge regarding their applications towards delivery into complex microbial biofilm structures is so far limited. The challenge is to demonstrate penetration and transport through the biofilm and its exopolysaccharide matrix. The ideal functionalization for penetration into mature biofilms is unexplored. In this paper, we present a novel set of rhodamine labelled βCD-polymers, with different charge moieties, i.e., neutral, anionic, and cationic, and explore their potential delivery into mature Staphylococcus epidermidis biofilms using multiphoton laser scanning microscopy (MPM). The S. epidermidis biofilms, being a medically relevant model organism, were stained with SYTO9. By using MPM, three-dimensional imaging and spectral investigation of the distribution of the βCD-polymers could be obtained. It was found that the cationic βCD-polymers showed significantly higher integration into the biofilms, compared to neutral and anionic functionalized βCDs. None of the carriers presented any inherent toxicity to the biofilms, meaning that the addition of rhodamine moiety does not affect the inertness of the delivery system. Taken together, this study demonstrates a novel approach by which delivery of fluorescently labelled CD nanoparticles to bacterial biofilms can be explored using MPM. Future studies should be undertaken investigating the potential in using cationic functionalization of CD based delivery systems for targeting anti-microbial effects in biofilms. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Ultrasound-assisted drug delivery for treatment of venous thrombosis: a case study.

PubMed

Marchiondo, Kathleen; Frink, Amber

2008-01-01

Ultrasound-assisted drug delivery is a relatively new medical intervention that combines low-intensity ultrasound waves with infusion of a thrombolytic agent directly into a thrombosed vein. Studies have demonstrated that clots are eradicated faster, more completely, and with fewer bleeding events with the use of ultrasound-assisted drug delivery for treatment of deep vein thrombosis compared to that of traditional therapies. Critical care nurses are responsible for preprocedure assessment and teaching and continuous monitoring of the patient during therapy for effectiveness and potential complications. An advantage of this technology from a nursing perspective is the minimal amount of time required for monitoring the drug delivery system, allowing greater focus on patient assessment and care.

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

PubMed

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

2014-07-01

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

Flying-qualities criteria for wings-level-turn maneuvering during an air-to-ground weapon delivery task

NASA Technical Reports Server (NTRS)

Sammonds, R. I.; Bunnell, J. W.

1981-01-01

A moving base simulator experiment demonstrated that a wings-level-turn control mode improved flying qualities for air to ground weapon delivery compared with those of a conventionally controlled aircraft. Evaluations of criteria for dynamic response for this system have shown that pilot ratings correlate well on the basis of equivalent time constant of the initial response. Ranges of this time constant, as well as digital system transport delays and lateral acceleration control authorities that encompassed level 1 through 3 handling qualities, were determined.

Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity.

PubMed

Tong, Xuwen; Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan

2016-10-01

In this study, the effects of nasal drug delivery device and the spray nozzle orientation on sprayed droplets deposition in a realistic human nasal cavity were numerically studied. Prior to performing the numerical investigation, an in-house designed automated actuation system representing mean adults actuation force was developed to produce realistic spray plume. Then, the spray plume development was filmed by high speed photography system, and spray characteristics such as spray cone angle, break-up length, and average droplet velocity were obtained through off-line image analysis. Continuing studies utilizing those experimental data as boundary conditions were applied in the following numerical spray simulations using a commercially available nasal spray device, which was inserted into a realistic adult nasal passage with external facial features. Through varying the particle releasing direction, the deposition fractions of selected particle sizes on the main nasal passage for targeted drug delivery were compared. The results demonstrated that the middle spray direction showed superior spray efficiency compared with upper or lower directions, and the 10µm agents were the most suitable particle size as the majority of sprayed agents can be delivered to the targeted area, the main passage. This study elaborates a comprehensive approach to better understand nasal spray mechanism and evaluate its performance for existing nasal delivery practices. Results of this study can assist the pharmaceutical industry to improve the current design of nasal drug delivery device and ultimately benefit more patients through optimized medications delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cesarean Section Rate in Singleton Primiparae and Related Factors in Beijing, China.

PubMed

Song, Geng; Wei, Yu-Mei; Zhu, Wei-Wei; Yang, Hui-Xia

2017-10-20

The cesarean section rate (CSR) has been a main concern worldwide. The present study aimed to investigate the CSR in Beijing, China, and to analyze the related factors of CS delivery. An observational study was conducted in 15 medical centers in Beijing using a systemic cluster sampling method. In total, 15,194 pregnancies were enrolled in the study between June 20, 2013 and November 30, 2013. Independent t-tests and Pearson's Chi-square test were used to examine differences between two groups, and related factors of the CSR were examined by multivariable logistic regression. The CSR was 41.9% (4471/10,671) in singleton primiparae. Women who were more than 35 years old had a 7.4-fold increased risk of CS delivery compared with women <25 years old (odd ratio [OR] = 7.388, 95% confidence interval [CI] = 5.561-9.816, P < 0.001). Prepregnancy obese women had a 2-fold increased risk of CS delivery compared with prepregnancy normal weight women (OR = 2.058, 95% CI = 1.640-2.584, P < 0.001). The excessive weight gain group had a 1.4-fold increased risk of CS delivery compared with the adequate weight gain group (OR = 1.422, 95% CI = 1.289-1.568, P < 0.001). Gestational diabetes mellitus (GDM) women and DM women had an increased risk of CS delivery (1.2- and 1.7-fold, respectively) compared with normal blood glucose women. Women who were born in rural areas had a lower risk of CS delivery than did those who were born in urban areas (OR = 0.696, 95% CI = 0.625-0.775, P < 0.001). The risk of CS delivery gradually increased with a decreasing education level. Neonates weighing 3000-3499 g had the lowest CSR (36.2%). Neonates weighing <2500 g had a 2-fold increased risk of CS delivery compared with neonates weighing 3000-3499 g (OR = 2.020, 95% CI = 1.537-2.656, P < 0.001). Neonates weighing ≥4500 g had an 8.3-fold increased risk of CS delivery compared with neonates weighing 3000-3499 g (OR = 8.313, 95% CI = 4.436-15.579, P < 0.001). Maternal age, prepregnancy body mass index, gestational weight gain, blood glucose levels, residence, education level, and singleton fetal birth weight are all factors that might significantly affect the CSR.

Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

PubMed Central

Rashid, Rehmana; Kim, Dong Wuk; Yousaf, Abid Mehmood; Mustapha, Omer; Din, Fakhar ud; Park, Jong Hyuck; Yong, Chul Soon; Oh, Yu-Kyoung; Youn, Yu Seok; Kim, Jong Oh; Choi, Han-Gon

2015-01-01

Background The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. Methods For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder. Results The drug existed in the crystalline form in SMSD, but was changed into an amorphous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 µm, respectively. All of these formulations significantly improved the aqueous solubility and dissolution in the order of solid SNEDDS ≥ SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability. Conclusion Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility. PMID:26491288

Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 2(3) factorial design and in vivo evaluation in rabbits.

PubMed

Soliman, Sara M; Abdelmalak, Nevine S; El-Gazayerly, Omaima N; Abdelaziz, Nabaweya

2016-06-01

Proniosomes offer a versatile vesicle drug delivery concept with potential for delivery of drugs via transdermal route. To develop proniosomal gel using cremophor RH 40 as non-ionic surfactant containing the antihypertensive drug lacidipine for transdermal delivery so as to avoid its extensive first pass metabolism and to improve its permeation through the skin. Proniosomes containing 1% lacidipine were prepared by the coacervation phase separation method, characterized, and optimized using a 2(3) full factorial design to define the optimum conditions to produce proniosomes with high entrapment efficiency, minimal vesicle size, and high-percentage release efficiency. The amount of cholesterol (X1), the amount of soya lecithin (X2), and the amount of cremophor RH 40 (X3) were selected as three independent variables. The system F4 was found to fulfill the maximum requisite of an optimum system because it had minimum vesicle size, maximum EE, maximum release efficiency, and maximum desirability. The optimized system (F4) was then converted to proniosomal gel using carbopol 940 (1% w/w). In vitro permeation through excised rabbit skin study revealed higher flux (6.48 ± 0.45) for lacidipine from the optimized proniosomal gel when compared with the corresponding emulgel (3.04 ± 0.13) mg/cm(2)/h. The optimized formulation was evaluated for its bioavailability compared with commercial product. Statistical analysis revealed significant increase in AUC (0 - α) 464.17 ± 113.15 ng h/ml compared with 209.02 ± 47.35 ng h/ml for commercial tablet. Skin irritancy and histopathological investigation of rat skin revealed its safety. Cremophor RH 40 proniosomal gel could be considered as very promising nanocarriers for transdermal delivery of lacidipine.

A continuous arc delivery optimization algorithm for CyberKnife m6.

PubMed

Kearney, Vasant; Descovich, Martina; Sudhyadhom, Atchar; Cheung, Joey P; McGuinness, Christopher; Solberg, Timothy D

2018-06-01

This study aims to reduce the delivery time of CyberKnife m6 treatments by allowing for noncoplanar continuous arc delivery. To achieve this, a novel noncoplanar continuous arc delivery optimization algorithm was developed for the CyberKnife m6 treatment system (CyberArc-m6). CyberArc-m6 uses a five-step overarching strategy, in which an initial set of beam geometries is determined, the robotic delivery path is calculated, direct aperture optimization is conducted, intermediate MLC configurations are extracted, and the final beam weights are computed for the continuous arc radiation source model. This algorithm was implemented on five prostate and three brain patients, previously planned using a conventional step-and-shoot CyberKnife m6 delivery technique. The dosimetric quality of the CyberArc-m6 plans was assessed using locally confined mutual information (LCMI), conformity index (CI), heterogeneity index (HI), and a variety of common clinical dosimetric objectives. Using conservative optimization tuning parameters, CyberArc-m6 plans were able to achieve an average CI difference of 0.036 ± 0.025, an average HI difference of 0.046 ± 0.038, and an average LCMI of 0.920 ± 0.030 compared with the original CyberKnife m6 plans. Including a 5 s per minute image alignment time and a 5-min setup time, conservative CyberArc-m6 plans achieved an average treatment delivery speed up of 1.545x ± 0.305x compared with step-and-shoot plans. The CyberArc-m6 algorithm was able to achieve dosimetrically similar plans compared to their step-and-shoot CyberKnife m6 counterparts, while simultaneously reducing treatment delivery times. © 2018 American Association of Physicists in Medicine.

Lactoferrin modified graphene oxide iron oxide nanocomposite for glioma-targeted drug delivery.

PubMed

Song, Meng-Meng; Xu, Huai-Liang; Liang, Jun-Xing; Xiang, Hui-Hui; Liu, Rui; Shen, Yu-Xian

2017-08-01

Targeting delivery of drugs in a specific manner represents a potential powerful technology in gliomas. Herein, we prepared a multifunctional targeted delivery system based on graphene oxide (GO) that contains a molecular bio-targeting ligand and superparamagnetic iron oxide nanoparticles on the surface of GO for magnetic targeting. Superparamagnetic Fe 3 O 4 nanoparticles was loaded on the surface of GO via chemical precipitation method to form GO@Fe 3 O 4 nanocomposites. Lactoferrin (Lf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells and vascular endothelial cell of the blood brain barrier, was chosen as the targeted ligand to construct the targeted delivery system Lf@GO@Fe 3 O 4 through EDC/NHS chemistry. With the confirmation of TEM, DLS and VSM, the resulting Lf@GO@Fe 3 O 4 had a size distribution of 200-1000nm and exhibited a superparamagnetic behavior. The nano delivery system had a high loading capacity and exhibited a pH-dependent release behavior. Compared with free DOX and DOX@GO@Fe 3 O 4 , Lf@GO@Fe 3 O 4 @DOX displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. The results demonstrated the potential utility of Lf conjugated GO@Fe 3 O 4 nanocomposites for therapeutic application in the treatment of gliomas. Copyright © 2017. Published by Elsevier B.V.

Effect of the Route of Administration and PEGylation of Poly(amidoamine) Dendrimers on Their Systemic and Lung Cellular Biodistribution.

PubMed

Zhong, Qian; Merkel, Olivia M; Reineke, Joshua J; da Rocha, Sandro R P

2016-06-06

There are many opportunities in the development of oral inhalation (oi) formulations for the delivery of small molecule therapeutics and biologics to and through the lungs. Nanocarriers have the potential to play a key role in advancing oi technologies and pushing the boundary of the pulmonary delivery market. In this work we investigate the effect of the route of administration and PEGylation on the systemic and lung cellular biodistribution of generation 3, amino-terminated poly(amidoamine) (PAMAM) dendrimers (G3NH2). Pharmacokinetic profiles show that the dendrimers reach their peak concentration in systemic circulation within a few hours after pulmonary delivery, independent of their chemistry (PEGylated or not), charge (+24 mV for G3NH2 vs -3.7 mV for G3NH2-24PEG1000), or size (5.1 nm for G3NH2 and 9.9 nm for G3NH2-24PEG1000). However, high density of surface modification with PEG enhances pulmonary absorption and the peak plasma concentration upon pulmonary delivery. The route of administration and PEGylation also significantly impact the whole body and local (lung cellular) distribution of the dendrimers. While ca. 83% of G3NH2 is found in the lungs upon pulmonary delivery at 6.5 h post administration, only 2% reached the lungs upon intravenous (iv) delivery. Moreover, no measurable concentration of either G3NH2 or G3NH2-24PEG1000 is found in the lymph nodes upon iv administration, while these are the tissues with the second highest mass distribution of dendrimers post pulmonary delivery. Dendrimer chemistry also significantly impacts the (cellular) distribution of the nanocarriers in the lung tissue. Upon pulmonary delivery, approximately 20% of the lung endothelial cells are seen to internalize G3NH2-24PEG1000, compared to only 6% for G3NH2. Conversely, G3NH2 is more readily taken up by lung epithelial cells (35%) when compared to its PEGylated counterpart (24%). The results shown here suggest that both the pulmonary route of administration and dendrimer chemistry combined can be used to passively target tissues and cell populations of great interest, and can thus be used as guiding principles in the development of dendrimer-based drug delivery strategies in the treatment of medically relevant diseases including lung ailments as well as systemic disorders.

Effect of the Route of Administration and PEGylation of Poly(amidoamine) Dendrimers on Their Systemic and Lung Cellular Biodistribution

PubMed Central

Zhong, Qian; Merkel, Olivia M.; Reineke, Joshua J.; da Rocha, Sandro R. P.

2017-01-01

There are many opportunities in the development of oral inhalation (oi) formulations for the delivery of small molecule therapeutics and biologics to and through the lungs. Nanocarriers have the potential to play a key role in advancing oi technologies and pushing the boundary of the pulmonary delivery market. In this work we investigate the effect of the route of administration and PEGylation on the systemic and lung cellular biodistribution of generation 3, amino-terminated poly(amidoamine) (PAMAM) dendrimers (G3NH2). Pharmacokinetic profiles show that the dendrimers reach their peak concentration in systemic circulation within a few hours after pulmonary delivery, independent of their chemistry (PEGylated or not), charge (+24 mV for G3NH2 vs −3.7 mV for G3NH2-24PEG1000), or size (5.1 nm for G3NH2 and 9.9 nm for G3NH2-24PEG1000). However, high density of surface modification with PEG enhances pulmonary absorption and the peak plasma concentration upon pulmonary delivery. The route of administration and PEGylation also significantly impact the whole body and local (lung cellular) distribution of the dendrimers. While ca. 83% of G3NH2 is found in the lungs upon pulmonary delivery at 6.5 h post administration, only 2% reached the lungs upon intravenous (iv) delivery. Moreover, no measurable concentration of either G3NH2 or G3NH2-24PEG1000 is found in the lymph nodes upon iv administration, while these are the tissues with the second highest mass distribution of dendrimers post pulmonary delivery. Dendrimer chemistry also significantly impacts the (cellular) distribution of the nanocarriers in the lung tissue. Upon pulmonary delivery, approximately 20% of the lung endothelial cells are seen to internalize G3NH2-24PEG1000, compared to only 6% for G3NH2. Conversely, G3NH2 is more readily taken up by lung epithelial cells (35%) when compared to its PEGylated counterpart (24%). The results shown here suggest that both the pulmonary route of administration and dendrimer chemistry combined can be used to passively target tissues and cell populations of great interest, and can thus be used as guiding principles in the development of dendrimer-based drug delivery strategies in the treatment of medically relevant diseases including lung ailments as well as systemic disorders. PMID:27148629

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

PubMed

Ghai, Damanjeet; Sinha, Vivek Ranjan

2012-07-01

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

Evaluation of Ocular Irritation and Bioavailability of Voriconazole Loaded Microemulsion.

PubMed

Kumar, Rakesh; Sinha, Vivek Ranjan

2017-01-01

Voriconazole (VCZ), a second-generation antifungal with excellent attributes like, broad-spectrum activity, targeted delivery, and tolerability. VCZ loaded microemulsion could be an effective strategy for efficient ocular delivery of the drug. To perform corneal irritation studies and in vivo delivery of VCZ microemulsion to establish its potential as an efficient ocular delivery system. Ocular irritancy was performed by HETCAM (Hen's Egg Test Chorio Allantoic Membrane) assay, corneal histopathology and Draize test. Ex vivo and in vivo studies were performed to determine permeation efficiency of VCZ microemulsion. The irritation studies suggested the non-irritant nature of the microemulsion. The ex vivo studies performed on excised cornea displayed significant enhancement in drug permeation/penetration from microemulsion in contrast to the drug suspension. Further, the in vivo study confirmed the higher availability of VCZ (from microemulsion) in aqueous humor with minimal nasolacrimal drainage (lower plasma drug content) when compared with the drug suspension. The non-irritant nature and high corneal permeation of VCZ encourages the role of microemulsion as a potential ocular delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

SU-F-T-518: Development and Characterization of a Gated Treatment System Implemented with An In-House Optical Tracking System and the Elekta Response Interface

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

Barraclough, B; Park, J; Li, F

2016-06-15

Purpose: To report the development and characterization of the first in-house gating system implemented with an optical tracking system (OTS) and the Elekta Response™ interface. Methods: The Response™ connects a patient tracking system with a linac, enabling the tracking system to control radiation delivery. The developed system uses an in-house OTS to monitor patient breathing. The OTS consists of two infrared-based cameras, tracking markers affixed on patient. It achieves gated or breath-held (BH) treatment by calling beam ON/OFF functions in the Response™ dynamic-link library (DLL). A 4D motion phantom was used to evaluate its dosimetric and time delay characteristics. Twomore » FF- and two FFF-IMRT beams were delivered in non-gated, BH and gated mode. The sinusoidal gating signal had a 6 sec period and 15 mm amplitude. The duty cycle included 10%, 20%, 30% and 50%. The BH signal was adapted from the sinusoidal wave by inserting 15 sec BHs. Each delivery was measured with a 2D diode array (MapCHECK™) and compared with the non-gated delivery using gamma analysis (3%). The beam ON/OFF time was captured using the service graphing utility of the linac. Results: The gated treatments were successfully delivered except the 10% duty cycle. The BH delivery had perfect agreement (100%) with non-gated delivery; the agreement of gated delivery decreased from 99% to 88% as duty cycle reduced from 50% to 20%. The beam on/off delay was on average 0.25/0.06 sec. The delivery time for the 50%, 30% and 20% duty cycle increased by 29%, 71% and 139%, respectively. No dosimetric or time delay difference was noticed between FF- and FFF-IMRT beams. Conclusion: The in-house gating system was successfully developed with dosimetric and time delay characteristics in line with published results for commercial systems. It will be an important platform for further research and clinical development of gated treatment.« less

Chitosan magnetic nanoparticles for drug delivery systems.

PubMed

Assa, Farnaz; Jafarizadeh-Malmiri, Hoda; Ajamein, Hossein; Vaghari, Hamideh; Anarjan, Navideh; Ahmadi, Omid; Berenjian, Aydin

2017-06-01

The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

A method for verification of treatment delivery in HDR prostate brachytherapy using a flat panel detector for both imaging and source tracking.

PubMed

Smith, Ryan L; Haworth, Annette; Panettieri, Vanessa; Millar, Jeremy L; Franich, Rick D

2016-05-01

Verification of high dose rate (HDR) brachytherapy treatment delivery is an important step, but is generally difficult to achieve. A technique is required to monitor the treatment as it is delivered, allowing comparison with the treatment plan and error detection. In this work, we demonstrate a method for monitoring the treatment as it is delivered and directly comparing the delivered treatment with the treatment plan in the clinical workspace. This treatment verification system is based on a flat panel detector (FPD) used for both pre-treatment imaging and source tracking. A phantom study was conducted to establish the resolution and precision of the system. A pretreatment radiograph of a phantom containing brachytherapy catheters is acquired and registration between the measurement and treatment planning system (TPS) is performed using implanted fiducial markers. The measured catheter paths immediately prior to treatment were then compared with the plan. During treatment delivery, the position of the (192)Ir source is determined at each dwell position by measuring the exit radiation with the FPD and directly compared to the planned source dwell positions. The registration between the two corresponding sets of fiducial markers in the TPS and radiograph yielded a registration error (residual) of 1.0 mm. The measured catheter paths agreed with the planned catheter paths on average to within 0.5 mm. The source positions measured with the FPD matched the planned source positions for all dwells on average within 0.6 mm (s.d. 0.3, min. 0.1, max. 1.4 mm). We have demonstrated a method for directly comparing the treatment plan with the delivered treatment that can be easily implemented in the clinical workspace. Pretreatment imaging was performed, enabling visualization of the implant before treatment delivery and identification of possible catheter displacement. Treatment delivery verification was performed by measuring the source position as each dwell was delivered. This approach using a FPD for imaging and source tracking provides a noninvasive method of acquiring extensive information for verification in HDR prostate brachytherapy.

A method for verification of treatment delivery in HDR prostate brachytherapy using a flat panel detector for both imaging and source tracking

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

Smith, Ryan L., E-mail: ryan.smith@wbrc.org.au; Millar, Jeremy L.; Franich, Rick D.

Purpose: Verification of high dose rate (HDR) brachytherapy treatment delivery is an important step, but is generally difficult to achieve. A technique is required to monitor the treatment as it is delivered, allowing comparison with the treatment plan and error detection. In this work, we demonstrate a method for monitoring the treatment as it is delivered and directly comparing the delivered treatment with the treatment plan in the clinical workspace. This treatment verification system is based on a flat panel detector (FPD) used for both pre-treatment imaging and source tracking. Methods: A phantom study was conducted to establish the resolutionmore » and precision of the system. A pretreatment radiograph of a phantom containing brachytherapy catheters is acquired and registration between the measurement and treatment planning system (TPS) is performed using implanted fiducial markers. The measured catheter paths immediately prior to treatment were then compared with the plan. During treatment delivery, the position of the {sup 192}Ir source is determined at each dwell position by measuring the exit radiation with the FPD and directly compared to the planned source dwell positions. Results: The registration between the two corresponding sets of fiducial markers in the TPS and radiograph yielded a registration error (residual) of 1.0 mm. The measured catheter paths agreed with the planned catheter paths on average to within 0.5 mm. The source positions measured with the FPD matched the planned source positions for all dwells on average within 0.6 mm (s.d. 0.3, min. 0.1, max. 1.4 mm). Conclusions: We have demonstrated a method for directly comparing the treatment plan with the delivered treatment that can be easily implemented in the clinical workspace. Pretreatment imaging was performed, enabling visualization of the implant before treatment delivery and identification of possible catheter displacement. Treatment delivery verification was performed by measuring the source position as each dwell was delivered. This approach using a FPD for imaging and source tracking provides a noninvasive method of acquiring extensive information for verification in HDR prostate brachytherapy.« less

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Preparation, characterization and in vivo evaluation of a combination delivery system based on hyaluronic acid/jeffamine hydrogel loaded with PHBV/PLGA blend nanoparticles for prolonged delivery of Teriparatide.

PubMed

Bahari Javan, Nika; Montazeri, Hamed; Rezaie Shirmard, Leila; Jafary Omid, Nersi; Barbari, Ghullam Reza; Amini, Mohsen; Ghahremani, Mohammad Hossein; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid

2017-04-01

In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD 50 of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-10-12

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

Novel Approaches in Formulation and Drug Delivery using Contact Lenses

PubMed Central

Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

2011-01-01

The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device PMID:24826007

Quality assurance: The 10-Group Classification System (Robson classification), induction of labor, and cesarean delivery.

PubMed

Robson, Michael; Murphy, Martina; Byrne, Fionnuala

2015-10-01

Quality assurance in labor and delivery is needed. The method must be simple and consistent, and be of universal value. It needs to be clinically relevant, robust, and prospective, and must incorporate epidemiological variables. The 10-Group Classification System (TGCS) is a simple method providing a common starting point for further detailed analysis within which all perinatal events and outcomes can be measured and compared. The system is demonstrated in the present paper using data for 2013 from the National Maternity Hospital in Dublin, Ireland. Interpretation of the classification can be easily taught. The standard table can provide much insight into the philosophy of care in the population of women studied and also provide information on data quality. With standardization of audit of events and outcomes, any differences in either sizes of groups, events or outcomes can be explained only by poor data collection, significant epidemiological variables, or differences in practice. In April 2015, WHO proposed that the TGCS (also known as the Robson classification) is used as a global standard for assessing, monitoring, and comparing cesarean delivery rates within and between healthcare facilities. Copyright © 2015. Published by Elsevier Ireland Ltd.

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

Development of self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system for liver cancer chemotherapy.

PubMed

Nittayacharn, Pinunta; Nasongkla, Norased

2017-07-01

The objective of this work was to develop self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system for liver cancer chemotherapy and studied the release profiles of doxorubicin (Dox) from different depot formulations. Tri-block copolymers of poly(ε-caprolactone), poly(D,L-lactide) and poly(ethylene glycol) named PLECs were successfully used as a biodegradable material to encapsulate Dox as the injectable local drug delivery system. Depot formation and encapsulation efficiency of these depots were evaluated. Results show that depots could be formed and encapsulate Dox with high drug loading content. For the release study, drug loading content (10, 15 and 20% w/w) and polymer concentration (25, 30, and 35% w/v) were varied. It could be observed that the burst release occurred within 1-2 days and this burst release could be reduced by physical mixing of hydroxypropyl-beta-cyclodextrin (HP-β-CD) into the depot system. The degradation at the surface and cross-section of the depots were examined by Scanning Electron Microscope (SEM). In addition, cytotoxicity of Dox-loaded depots and blank depots were tested against human liver cancer cell lines (HepG2). Dox released from depots significantly exhibited potent cytotoxic effect against HepG2 cell line compared to that of blank depots. Results from this study reveals an important insight in the development of injectable drug delivery system for liver cancer chemotherapy. Schematic diagram of self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system and in vitro characterizations. (a) Dox-loaded PLEC depots could be formed with more than 90% of sustained-release Dox at 25% polymer concentration and 20% Dox-loading content. The burst release occurred within 1-2 days and could be reduced by physical mixing of hydroxypropyl-beta-cyclodextrin (HP-β-CD) into the depot system. (b) Dox released from depots significantly exhibited potent cytotoxic effect against human liver cancer cell lines (HepG2 cell line) compared to that of blank depots. (c) Dox-loaded depots showed bulk erosion with hollow core at day 60.

SU-E-T-268: Differences in Treatment Plan Quality and Delivery Between Two Commercial Treatment Planning Systems for Volumetric Arc-Based Radiation Therapy

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

Chen, S; Zhang, H; Zhang, B

2015-06-15

Purpose: To clinically evaluate the differences in volumetric modulated arc therapy (VMAT) treatment plan and delivery between two commercial treatment planning systems. Methods: Two commercial VMAT treatment planning systems with different VMAT optimization algorithms and delivery approaches were evaluated. This study included 16 clinical VMAT plans performed with the first system: 2 spine, 4 head and neck (HN), 2 brain, 4 pancreas, and 4 pelvis plans. These 16 plans were then re-optimized with the same number of arcs using the second treatment planning system. Planning goals were invariant between the two systems. Gantry speed, dose rate modulation, MLC modulation, planmore » quality, number of monitor units (MUs), VMAT quality assurance (QA) results, and treatment delivery time were compared between the 2 systems. VMAT QA results were performed using Mapcheck2 and analyzed with gamma analysis (3mm/3% and 2mm/2%). Results: Similar plan quality was achieved with each VMAT optimization algorithm, and the difference in delivery time was minimal. Algorithm 1 achieved planning goals by highly modulating the MLC (total distance traveled by leaves (TL) = 193 cm average over control points per plan), while maintaining a relatively constant dose rate (dose-rate change <100 MU/min). Algorithm 2 involved less MLC modulation (TL = 143 cm per plan), but greater dose-rate modulation (range = 0-600 MU/min). The average number of MUs was 20% less for algorithm 2 (ratio of MUs for algorithms 2 and 1 ranged from 0.5-1). VMAT QA results were similar for all disease sites except HN plans. For HN plans, the average gamma passing rates were 88.5% (2mm/2%) and 96.9% (3mm/3%) for algorithm 1 and 97.9% (2mm/2%) and 99.6% (3mm/3%) for algorithm 2. Conclusion: Both VMAT optimization algorithms achieved comparable plan quality; however, fewer MUs were needed and QA results were more robust for Algorithm 2, which more highly modulated dose rate.« less

Racial and Ethnic Disparities in the Pregnancies of Women With Systemic Lupus Erythematosus.

PubMed

Clowse, Megan E B; Grotegut, Chad

2016-10-01

Both systemic lupus erythematosus (SLE; lupus) and pregnancy individually have significant racial disparities, with black women experiencing higher rates of complications, yet no large studies have focused on the impact of race/ethnicity on pregnancy outcomes among women with lupus. Using the Nationwide Inpatient Sample (NIS) for 2008-2010, pregnancy delivery discharges were identified and pregnancy outcomes were compared for women with lupus by maternal race/ethnicity. Adjusted odds ratios were used to compare pregnancy outcomes between black and white or Hispanic and white women with lupus. In this period, the NIS included 13,553 deliveries with lupus and 12,510,565 deliveries without lupus. Compared to white women with lupus, black and Hispanic women had higher rates of chronic hypertension, chronic renal failure, pneumonia, and acute renal failure. There was a high degree of pregnancy complication in all women with lupus, but especially in black and Hispanic women, with more than 40% cesarean-section delivery; preterm labor in 14.3% of white, 24.7% of black (odds ratio [OR] 1.97), and 20.6% of Hispanic (OR 1.56) deliveries; and preeclampsia and gestational hypertension in almost 20% of black and Hispanic pregnancies. After adjustment for predictors of pregnancy outcomes and racial differences in nonlupus pregnancy, black and Hispanic women with lupus had higher than expected rates of preeclampsia, preterm labor, and fetal growth restriction. Black and Hispanic women with lupus have disproportionately poor pregnancy outcomes. This study suggests that identifying the key causes of these differences and targeting interventions to the women of greatest need is an essential next step. © 2016, American College of Rheumatology.

Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo.

PubMed

Klippstein, Rebecca; Wang, Julie Tzu-Wen; El-Gogary, Riham I; Bai, Jie; Mustafa, Falisa; Rubio, Noelia; Bansal, Sukhvinder; Al-Jamal, Wafa T; Al-Jamal, Khuloud T

2015-09-01

Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil-cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non-PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Wireless Text Messaging System Improves Communication for Neonatal Resuscitation.

PubMed

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

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

Development of bupivacaine decorated reduced graphene oxide and its local anesthetic effect-In vivo study.

PubMed

Zhang, Zhi; Zhang, Xin; Li, Aixiang; Ma, Chuangen

2018-03-01

The present works aims to develop bupivacaine modified reduced graphene oxide (BPV/RGO), and comparative evaluation of their anesthetic effect with free bupivacaine (BPV). The prepared BPV/RGO was studied by using various spectroscopic and microscopic characterization studies. In vitro drug release from BPV/RGO was studied using HPLC analysis. The cytotoxicity of BPV/RGO was studied against fibroblast (3T3) cells. In vivo evaluation of anesthetic effects was performed on animal models. BPV/RGO showed a prolonged in vitro release and lower cytotoxicity when compared to free BPV. Also, BPV/RGO showed a significantly prolonged analgesic effect when compared to free BPV. Further, the prepared BPV/RGO drug delivery system demonstrated to function as gifted to overcome the drawbacks of free BPV and other available drug delivery systems by prolonging the anesthetic effect with poor cytotoxicity. Copyright © 2018. Published by Elsevier B.V.

Lessons Learned from Gemcitabine: Impact of Therapeutic Carrier Systems and Gemcitabine's Drug Conjugates on Cancer Therapy.

PubMed

Dyawanapelly, Sathish; Kumar, Animesh; Chourasia, Manish K

2017-01-01

Currently, drug delivery systems have a high impact in cancer therapy and are receiving more attention than conventional cancer treatment modalities. Compared with current cancer therapies, gemcitabine (2', 2'-difluoro-2'-deoxycytidine) has been proven to be an effective chemotherapeutic agent against pancreatic, colon, bladder, breast, ovarian, non-small-cell lung, and head and neck cancers in combination with other anticancer agents. To improve the safety and efficacy of cytotoxic drugs, several drug delivery systems have been explored. This review outlines the recent work directed toward gemcitabine delivery systems for cancer therapy, including aerosols, polymeric nanoparticles, liposomes, microparticles, carbon nanotubes, and multifunctional theranostic nanomedicines. It also provides insight into the design and development of gemcitabine conjugation for safe and effective cancer therapy. Despite the clinical promises of gemcitabine, many therapeutic challenges remain. Specifically, its therapeutic use in cancer chemotherapy is impeded by a short biological half-life, caused by its rapid metabolism, and resistance due to increased expression of ribonucleotide reductase. In our opinion, many research investigations have contributed to improve the selectivity and efficacy of gemcitabine. This combined approach of drug delivery systems and gemcitabine conjugates has shown promising efficacy in preclinical models and significant potential for future clinical cancer-therapeutic applications. Also, these strategies overcome most of the aforementioned limits of gemcitabine.

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release.

PubMed

Cunningham, Alexander J; Robinson, Mattieu; Banquy, Xavier; Leblond, Jeanne; Zhu, X X

2018-03-05

Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed toward breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG) 4 ) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC 50 and highest cellular internalization, indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.

Comparing human peritoneal fluid and phosphate-buffered saline for drug delivery: do we need bio-relevant media?

PubMed

Bhusal, Prabhat; Rahiri, Jamie Lee; Sua, Bruce; McDonald, Jessica E; Bansal, Mahima; Hanning, Sara; Sharma, Manisha; Chandramouli, Kaushik; Harrison, Jeff; Procter, Georgina; Andrews, Gavin; Jones, David S; Hill, Andrew G; Svirskis, Darren

2018-06-01

An understanding of biological fluids at the site of administration is important to predict the fate of drug delivery systems in vivo. Little is known about peritoneal fluid; therefore, we have investigated this biological fluid and compared it to phosphate-buffered saline, a synthetic media commonly used for in vitro evaluation of intraperitoneal drug delivery systems. Human peritoneal fluid samples were analysed for electrolyte, protein and lipid levels. In addition, physicochemical properties were measured alongside rheological parameters. Significant inter-patient variations were observed with regard to pH (p < 0.001), buffer capacity (p < 0.05), osmolality (p < 0.001) and surface tension (p < 0.05). All the investigated physicochemical properties of peritoneal fluid differed from phosphate-buffered saline (p < 0.001). Rheological examination of peritoneal fluid demonstrated non-Newtonian shear thinning behaviour and predominantly exhibited the characteristics of an entangled network. Inter-patient and inter-day variability in the viscosity of peritoneal fluid was observed. The solubility of the local anaesthetic lidocaine in peritoneal fluid was significantly higher (p < 0.05) when compared to phosphate-buffered saline. Interestingly, the dissolution rate of lidocaine was not significantly different between the synthetic and biological media. Importantly, and with relevance to intraperitoneal drug delivery systems, the sustained release of lidocaine from a thermosensitive gel formulation occurred at a significantly faster rate into peritoneal fluid. Collectively, these data demonstrate the variation between commonly used synthetic media and human peritoneal fluid. The differences in drug release rates observed illustrate the need for bio-relevant media, which ultimately would improve in vitro-in vivo correlation.

Alternate Service Delivery Models in Cancer Genetic Counseling: A Mini-Review.

PubMed

Buchanan, Adam Hudson; Rahm, Alanna Kulchak; Williams, Janet L

2016-01-01

Demand for cancer genetic counseling has grown rapidly in recent years as germline genomic information has become increasingly incorporated into cancer care, and the field has entered the public consciousness through high-profile celebrity publications. Increased demand and existing variability in the availability of trained cancer genetics clinicians place a priority on developing and evaluating alternate service delivery models for genetic counseling. This mini-review summarizes the state of science regarding service delivery models, such as telephone counseling, telegenetics, and group counseling. Research on comparative effectiveness of these models in traditional individual, in-person genetic counseling has been promising for improving access to care in a manner acceptable to patients. Yet, it has not fully evaluated the short- and long-term patient- and system-level outcomes that will help answer the question of whether these models achieve the same beneficial psychosocial and behavioral outcomes as traditional cancer genetic counseling. We propose a research agenda focused on comparative effectiveness of available service delivery models and how to match models to patients and practice settings. Only through this rigorous research can clinicians and systems find the optimal balance of clinical quality, ready and secure access to care, and financial sustainability. Such research will be integral to achieving the promise of genomic medicine in oncology.

Human fetal bone cells in delivery systems for bone engineering.

PubMed

Tenorio, Diene M H; Scaletta, Corinne; Jaccoud, Sandra; Hirt-Burri, Nathalie; Pioletti, Dominique P; Jaques, Bertrand; Applegate, Lee Ann

2011-11-01

The aim of this study was to culture human fetal bone cells (dedicated cell banks of fetal bone derived from 14 week gestation femurs) within both hyaluronic acid gel and collagen foam, to compare the biocompatibility of both matrices as potential delivery systems for bone engineering and particularly for oral application. Fetal bone cell banks were prepared from one organ donation and cells were cultured for up to 4 weeks within hyaluronic acid (Mesolis®) and collagen foams (TissueFleece®). Cell survival and differentiation were assessed by cell proliferation assays and histology of frozen sections stained with Giemsa, von Kossa and ALP at 1, 2 and 4 weeks of culture. Within both materials, fetal bone cells could proliferate in three-dimensional structure at ∼70% capacity compared to monolayer culture. In addition, these cells were positive for ALP and von Kossa staining, indicating cellular differentiation and matrix production. Collagen foam provides a better structure for fetal bone cell delivery if cavity filling is necessary and hydrogels would permit an injectable technique for difficult to treat areas. In all, there was high biocompatibility, cellular differentiation and matrix deposition seen in both matrices by fetal bone cells, allowing for easy cell delivery for bone stimulation in vivo. Copyright © 2011 John Wiley & Sons, Ltd.

Through-Metal-Wall Power Delivery and Data Transmission for Enclosed Sensors: A Review

PubMed Central

Yang, Ding-Xin; Hu, Zheng; Zhao, Hong; Hu, Hai-Feng; Sun, Yun-Zhe; Hou, Bao-Jian

2015-01-01

The aim of this review was to assess the current viable technologies for wireless power delivery and data transmission through metal barriers. Using such technologies sensors enclosed in hermetical metal containers can be powered and communicate through exterior power sources without penetration of the metal wall for wire feed-throughs. In this review, we first discuss the significant and essential requirements for through-metal-wall power delivery and data transmission and then we: (1) describe three electromagnetic coupling based techniques reported in the literature, which include inductive coupling, capacitive coupling, and magnetic resonance coupling; (2) present a detailed review of wireless ultrasonic through-metal-wall power delivery and/or data transmission methods; (3) compare various ultrasonic through-metal-wall systems in modeling, transducer configuration and communication mode with sensors; (4) summarize the characteristics of electromagnetic-based and ultrasound-based systems, evaluate the challenges and development trends. We conclude that electromagnetic coupling methods are suitable for through thin non-ferromagnetic metal wall power delivery and data transmission at a relatively low data rate; piezoelectric transducer-based ultrasonic systems are particularly advantageous in achieving high power transfer efficiency and high data rates; the combination of more than one single technique may provide a more practical and reliable solution for long term operation. PMID:26694392

Temperature-sensitive microemulsion gel: an effective topical delivery system for simultaneous delivery of vitamins C and E.

PubMed

Rozman, Branka; Zvonar, Alenka; Falson, Francoise; Gasperlin, Mirjana

2009-01-01

Microemulsions (ME)--nanostructured systems composed of water, oil, and surfactants--have frequently been used in attempts to increase cutaneous drug delivery. The primary objective addressed in this work has been the development of temperature-sensitive microemulsion gel (called gel-like ME), as an effective and safe delivery system suitable for simultaneous topical application of a hydrophilic vitamin C and a lipophilic vitamin E. By changing water content of liquid o/w ME (o/w ME), a gel-like ME with temperature-sensitive rheological properties was formed. The temperature-driven changes in its microstructure were confirmed by rotational rheometry, viscosity measurements, and droplet size determination. The release studies have shown that the vitamins' release at skin temperature from gel-like ME were comparable to those from o/w ME and were much faster and more complete than from o/w ME conventionally thickened with polymer (o/w ME carbomer). According to effectiveness in skin delivery of both vitamins, o/w ME was found the most appropriate, followed by gel-like ME and by o/w ME carbomer, indicating that no simple correlation between vitamins release and skin absorption could be found. The cytotoxicity studies revealed good cell viability after exposure to ME and confirmed all tested microemulsions as nonirritant.

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

Does vacuum delivery carry a higher risk of shoulder dystocia? Review and meta-analysis of the literature.

PubMed

Dall'Asta, Andrea; Ghi, Tullio; Pedrazzi, Giuseppe; Frusca, Tiziana

2016-09-01

Vacuum extractor has been increasingly used over the last decades and is acknowledged as a risk factor for shoulder dystocia (SD). In this meta-analysis we assess the actual risk of SD following a vacuum delivery compared to spontaneous vaginal delivery (SVD) and forceps. Systematic literature search (English literature only) on MEDLINE, EMBASE, ScienceDirect, the Cochrane library and ClinicalTrials.gov conducted up to May 2015. Key search terms included: Operative/Vacuum/Forceps delivery [Mesh] and shoulder dystocia and subheadings. 2 stage-process study selection. We included only studies where data concerning the occurrence of SD following operative vaginal delivery were reported as adjusted odds ratio (AOR) and no significant difference in confounding factors for SD was recorded. Included trials clustered according to the delivery mode (1) vacuum vs. SVD, (2) forceps vs. vacuum. Methodological quality of each study evaluated with the Newcastle-Ottawa System (NOS). 87 potentially relevant papers. After applying inclusion and exclusion criteria only 7 were selected for the meta-analysis. Vacuum delivery appeared associated with a higher risk of SD than SVD in both fixed and random model (OR 2.87 and 2.98 respectively). No difference in the rate of SD was found between vacuum and forceps (p>0.05). Vacuum extractor carries an increased risk of SD compared with spontaneous vaginal delivery whereas the occurrence of SD does not seem to vary following vacuum or forceps. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Health care quality, access, cost, workforce, and surgical education: the ultimate perfect storm.

PubMed

Schwartz, Marshall Z

2012-01-01

The discussions on health care reform over the past two years have focused on cost containment while trying to maintain quality of care. Focusing on just cost and quality unfortunately does not address other very important factors that impact on our health care delivery system. Availability of a well-trained workforce, maintaining the sophisticated medical/surgical education system, and ultimately access to quality care by the public are critical to maintaining and enhancing our health care delivery system. Unfortunately, all five of these components are under at risk. Thus, we have evolving the ultimate perfect storm affecting our health care delivery system. Although not ideal and given the uniqueness of our population and their expectations, our current delivery system is excellent compared to other countries. However, the cost of our current system is rising at an alarming rate. Currently, health care consumes 17% of our gross domestic product. If our system is not revised this will continue to rise and by 2025 it will consume 48%. The dilemma, given the current state of our overall economy and rising debt, is how to address this major problem. Unfortunately, the Affordable Care Act, which is now law, does not address most of the issues and the cost was initially grossly under estimated. Furthermore, the law does not address the issues of workforce, maintaining our medical education system or ultimately, access. A major revision of our system will be necessary to truly create a system that protects and enhances all five of the components of our health care delivery system. To effectively accomplish this will require addressing those issues that lead to wasteful spending and diversion of our health care dollars to profit instead of care. Improved and efficient delivery systems that reduce complications, reduction of duplication of tertiary and quaternary programs or services within the same markets (i.e. regionalization of care), health insurance reform, and tort reform collectively could save hundreds of billion dollars per year! These changes may not be easy to accomplish politically but will be essential to save what is likely the best health care system in the world. Copyright © 2012. Published by Elsevier Inc.

Poster – 13: Evaluation of an in-house CCD camera film dosimetry imaging system for small field deliveries

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

Lalonde, Michel; Alexander, Kevin; Olding, Tim

Purpose: Radiochromic film dosimetry is a standard technique used in clinics to verify modern conformal radiation therapy delivery, and sometimes in research to validate other dosimeters. We are using film as a standard for comparison as we improve high-resolution three-dimensional gel systems for small field dosimetry; however, precise film dosimetry can be technically challenging. We report here measurements for fractionated stereotactic radiation therapy (FSRT) delivered using volumetric modulated arc therapy (VMAT) to investigate the accuracy and reproducibility of film measurements with a novel in-house readout system. We show that radiochromic film can accurately and reproducibly validate FSRT deliveries and alsomore » benchmark our gel dosimetry work. Methods: VMAT FSRT plans for metastases alone (PTV{sub MET}) and whole brain plus metastases (WB+PTV{sub MET}) were delivered onto a multi-configurational phantom with a sheet of EBT3 Gafchromic film inserted mid-plane. A dose of 400 cGy was prescribed to 4 small PTV{sub MET} structures in the phantom, while a WB structure was prescribed a dose of 200 cGy in the WB+PTV{sub MET} iterations. Doses generated from film readout with our in-house system were compared to treatment planned doses. Each delivery was repeated multiple times to assess reproducibility. Results and Conclusions: The reproducibility of film optical density readout was excellent throughout all experiments. Doses measured from the film agreed well with plans for the WB+PTV{sub MET} delivery. But, film doses for PTV{sub MET} only deliveries were significantly below planned doses. This discrepancy is due to stray/scattered light perturbations in our system during readout. Corrections schemes will be presented.« less

It takes a village: Exploring the impact of social determinants on delivery system outcomes for heart failure patients.

PubMed

Knighton, Andrew J; Savitz, Lucy A; Benuzillo, Jose; VanDerslice, James A

2017-06-24

Local social determinants may act as effect modifiers for the impact of neighborhood material deprivation on patient-level healthcare outcomes. The objective of this study was to understand the mediating effect of local social determinants on neighborhood material deprivation and delivery outcomes in heart failure (HF) patients. A retrospective cohort study was conducted using 4737 HF patients receiving inpatient care (n=6065 encounters) from an integrated healthcare delivery system from 2010 to 2014. Outcomes included post-discharge mortality, readmission risk and length of stay. Deprivation was measured using an area deprivation index by address of residence. Effect modifications measured included urban-rural residency and faith identification using generalized linear regression models. Patient-level data was drawn from the delivery system data warehouse. Faith identification had a significant protective effect on HF patients from deprived areas, lowering 30-day mortality odds by one-third over patients who did not identify with a faith (OR 0.35 95%CI:0.12-0.98;p=0.05). Significant effects persisted at the 90 and 180-day timeframes. In rural areas, lack of faith identification had a multiplicative effect on 30-day mortality for deprived patients (OR 14.0 95%CI:1.47-132.7;p=0.02). No significant effects were noted for other healthcare outcomes. The lack of expected association between area deprivation and healthcare outcomes in some communities may be explained by the presence of effect modifiers. Understanding existing effect modifiers for area deprivation in local communities that delivery systems serve can inform targeted quality improvement. These factors should also be considered when comparing delivery system performance for reimbursement and in population health management. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-E-T-545: A MLC-Equipped Robotic Radiosurgery-Radiotherapy Combined System in Treating Hepatic Lesions: Delivery Efficiency as Compared to a Standard Linac for Treating Hepatic Lesions

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

Jin, L; Price, R; Wang, L

Purpose: The CyberKnife (CK) M6 Series introduced a mulitleaf collimator (MLC) beam for extending its capability to the conventional radiotherapy. This work is to investigate delivery efficiency of this system as compared to a standard Varian linac when treating hepatic lesions. Methods: Nine previously treated patients were divided into three groups with three patients in each. Group one: fractionated radiotherapy; Group two: SBRT-like treatments and Group three: fractionated radiotherapy targeting two PTVs. The clinically used plans were generated with the Eclipse treatment planning system (TPS). We re-planned these cases using a Mulitplan (MP) TPS for the CK M6 and normalizedmore » to the same PTV dose coverage. CK factors (CF) (defined as modulation scaling factor in this work), number of nodes (NN), number of MLC segments (NS) and beam delivery time (BT) with an estimated image interval of 60 seconds, were used for evaluation of delivery efficiency. Results: Generated plans from the MP and Eclipse TPS demonstrated the similar quality in terms of PTV confomality index, minimum and maximum PTV doses, and doses received by critical structures. Group one: CF ranged from 8.1 to 8.7, NN from 30 to 40, NS from 120 to 155 and BT from 20 to 23 minutes; group two: CF from 4.7 to 8.5, NN from 15 to 19, NS from 82 to 141 and BT from 18 to 24 minutes; and group three: CF from 7.9 to 10, NN from 47 to 49, NS from 110 to 113 and BT from 20 to 22 minutes. Conclusions: Delivery time is longer for the CK M6 than for the Varian linac (7.8 to 13.7 minutes). Further investigation will be necessary to determine if a PTV reduction from the tracking feature will shorten the delivery time without decreasing plan quality.« less

Oral transmucosal delivery of naratriptan.

PubMed

Sattar, Mohammed; Lane, Majella E

2016-11-30

Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol ® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 ® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery.

PubMed

Ma, Yiming; Fuchs, Adrian V; Boase, Nathan R B; Rolfe, Barbara E; Coombes, Allan G A; Thurecht, Kristofer J

2015-08-01

Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

A feasibility study of cerebral oximetry during in-hospital mechanical and manual cardiopulmonary resuscitation*.

PubMed

Parnia, Sam; Nasir, Asad; Ahn, Anna; Malik, Hanan; Yang, Jie; Zhu, Jiawen; Dorazi, Francis; Richman, Paul

2014-04-01

A major hurdle limiting the ability to improve the quality of resuscitation has been the lack of a noninvasive real-time detection system capable of monitoring the quality of cerebral and other organ perfusion, as well as oxygen delivery during cardiopulmonary resuscitation. Here, we report on a novel system of cerebral perfusion targeted resuscitation. An observational study evaluating the role of cerebral oximetry (Equanox; Nonin, Plymouth, MI, and Invos; Covidien, Mansfield, MA) as a real-time marker of cerebral perfusion and oxygen delivery together with the impact of an automated mechanical chest compression system (Life Stat; Michigan Instruments, Grand Rapids, MI) on oxygen delivery and return of spontaneous circulation following in-hospital cardiac arrest. Tertiary medical center. In-hospital cardiac arrest patients (n = 34). Cerebral oximetry provided real-time information regarding the quality of perfusion and oxygen delivery. The use of automated mechanical chest compression device (n = 12) was associated with higher regional cerebral oxygen saturation compared with manual chest compression device (n = 22) (53.1% ± 23.4% vs 24% ± 25%, p = 0.002). There was a significant difference in mean regional cerebral oxygen saturation (median % ± interquartile range) in patients who achieved return of spontaneous circulation (n = 15) compared with those without return of spontaneous circulation (n = 19) (47.4% ± 21.4% vs 23% ± 18.42%, p < 0.001). After controlling for patients achieving return of spontaneous circulation or not, significantly higher mean regional cerebral oxygen saturation levels during cardiopulmonary resuscitation were observed in patients who were resuscitated using automated mechanical chest compression device (p < 0.001). The integration of cerebral oximetry into cardiac arrest resuscitation provides a novel noninvasive method to determine the quality of cerebral perfusion and oxygen delivery to the brain. The use of automated mechanical chest compression device during in-hospital cardiac arrest may lead to improved oxygen delivery and organ perfusion.

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

PubMed Central

Cole, Grace; McCaffrey, Joanne; Ali, Ahlam A.; McBride, John W.; McCrudden, Cian M.; Vincente-Perez, Eva M.; Donnelly, Ryan F.; McCarthy, Helen O.

2017-01-01

ABSTRACT DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application. PMID:27846370

Thiomers for oral delivery of hydrophilic macromolecular drugs.

PubMed

Bernkop-Schnürch, Andreas; Hoffer, Martin H; Kafedjiiski, Krum

2004-11-01

In recent years thiolated polymers (thiomers) have appeared as a promising new tool in oral drug delivery. Thiomers are obtained by the immobilisation of thio-bearing ligands to mucoadhesive polymeric excipients. By the formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of thiomers are up to 130-fold improved compared with the corresponding unmodified polymers. Owing to the formation of inter- and intramolecular disulfide bonds within the thiomer itself, matrix tablets and particulate delivery systems show strong cohesive properties, resulting in comparatively higher stability, prolonged disintegration times and a more controlled drug release. The permeation of hydrophilic macromolecular drugs through the gastrointestinal (GI) mucosa can be improved by the use of thiomers. Furthermore, some thiomers exhibit improved inhibitory properties towards GI peptidases. The efficacy of thiomers in oral drug delivery has been demonstrated by various in vivo studies. A pharmacological efficacy of 1%, for example, was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Furthermore, tablets comprising a thiomer and pegylated insulin resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Low-molecular-weight heparin embedded in thiolated polycarbophil led to an absolute bioavailability of > or = 20% after oral administration to rats. In these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. These results indicate drug carrier systems based on thiomers appear to be a promising tool for oral delivery of hydrophilic macromolecular drugs.

Microparticles, microcapsules and microspheres: A review of recent developments and prospects for oral delivery of insulin.

PubMed

Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

2018-02-15

Diabetes mellitus is a chronic metabolic health disease affecting the homeostasis of blood sugar levels. However, subcutaneous injection of insulin can lead to patient non-compliance, discomfort, pain and local infection. Sub-micron sized drug delivery systems have gained attention in oral delivery of insulin for diabetes treatment. In most of the recent literature, the terms "microparticles" and "nanoparticle" refer to particles where the dimensions of the particle are measured in micrometers and nanometers respectively. For instance, insulin-loaded particles are defined as microparticles with size larger than 1 μm by most of the research groups. The size difference between nanoparticles and microparticles proffers numerous effects on the drug loading efficiency, aggregation, permeability across the biological membranes, cell entry and tissue retention. For instance, microparticulate drug delivery systems have demonstrated a number of advantages including protective effect against enzymatic degradation, enhancement of peptide stability, site-specific and controlled drug release. Compared to nanoparticulate drug delivery systems, microparticulate formulations can facilitate oral absorption of insulin by paracellular, transcellular and lymphatic routes. In this article, we review the current status of microparticles, microcapsules and microspheres for oral administration of insulin. A number of novel techniques including layer-by-layer coating, self-polymerisation of shell, nanocomposite microparticulate drug delivery system seem to be promising for enhancing the oral bioavailability of insulin. This review draws several conclusions for future directions and challenges to be addressed for optimising the properties of microparticulate drug formulations and enhancing their hypoglycaemic effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential use of lasers for penetrating keratoplasty.

PubMed

Thompson, K P; Barraquer, E; Parel, J M; Loertscher, H; Pflugfelder, S; Roussel, T; Holland, S; Hanna, K

1989-07-01

Experimental corneal trephination has been achieved with the 193 nm argon fluoride excimer and 2.9 microns hydrogen fluoride and Er:YAG laser systems. Compared with metal blades and other lasers, the 193 nm excimer laser creates the best quality corneal excision, but has a relatively slow etch rate through the stroma, and its use requires toxic gas. The mid-infrared laser systems trephine the cornea in less than 10 seconds, but cause a 10 microns to 15 microns zone of adjacent stromal damage and create wounds that are approximately 2.5 times larger than wounds made by metal scalpels. The wavelength and laser pulse duration influence the cutting characteristics of the laser. Optical delivery systems using an axicon lens, a rotating slit, and a computer controlled scanning optical system have been developed for penetrating keratoplasty. Selection of the optimal laser system for penetrating keratoplasty must await further experimental studies. Refinements of the laser cavity and delivery system are necessary before clinical studies can begin. A carefully controlled randomized clinical trial comparing laser trephination with conventional mechanical trephines will be necessary to determine the safety and efficacy of a laser trephination system.

Ultrasound-stimulated drug delivery for treatment of residual disease after incomplete resection of head and neck cancer.

PubMed

Sorace, Anna G; Korb, Melissa; Warram, Jason M; Umphrey, Heidi; Zinn, Kurt R; Rosenthal, Eben; Hoyt, Kenneth

2014-04-01

Microbubbles triggered with localized ultrasound (US) can improve tumor drug delivery and retention. Termed US-stimulated drug delivery, this strategy was applied to head and neck cancer (HNC) in a post-surgical tumor resection model. Luciferase-positive HNC squamous cell carcinoma (SCC) was implanted in the flanks of nude athymic mice (N = 24) that underwent various degrees of surgical tumor resection (0%, 50% or 100%). After surgery, animals received adjuvant therapy with cetuximab-IRDye alone, or cetuximab-IRDye in combination with US-stimulated drug delivery or saline injections (control) on days 4, 7 and 10. Tumor drug delivery was assessed on days 0, 4, 7, 10, 14 and 17 with an in vivo fluorescence imaging system, and tumor viability was evaluated at the same times with in vivo bioluminescence imaging. Tumor caliper measurements occurred two times per week for 24 d. Optical imaging revealed that in the 50% tumor resection group, US-stimulated drug delivery resulted in a significant increase in cetuximab delivery compared with administration of drug alone on day 10 (day of peak fluorescence) (p = 0.03). Tumor viability decreased in all groups that received cetuximab-IRDye in combination with US-stimulated drug delivery, compared with the group that received only the drug. After various degrees of surgical resection, this novel study reports positive improvements in drug uptake in the residual cancer cells when drug delivery is stimulated with US. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Construction of a controlled-release delivery system for pesticides using biodegradable PLA-based microcapsules.

PubMed

Liu, Baoxia; Wang, Yan; Yang, Fei; Wang, Xing; Shen, Hong; Cui, Haixin; Wu, Decheng

2016-08-01

Conventional pesticides usually need to be used in more than recommended dosages due to their loss and degradation, which results in a large waste of resources and serious environmental pollution. Encapsulation of pesticides in biodegradable carriers is a feasible approach to develop environment-friendly and efficient controlled-release delivery system. In this work, we fabricated three kinds of polylactic acid (PLA) carriers including microspheres, microcapsules, and porous microcapsules for controlled delivery of Lambda-Cyhalothrin (LC) via premix membrane emulsification (PME). The microcapsule delivery system had better water dispersion than the other two systems. Various microcapsules with a high LC contents as much as 40% and tunable sizes from 0.68 to 4.6μm were constructed by manipulating the process parameters. Compared with LC technical and commercial microcapsule formulation, the microcapsule systems showed a significantly sustained release of LC for a longer period. The LC release triggered by LC diffusion and matrix degradation could be optimally regulated by tuning LC contents and particle sizes of the microcapsules. This multi-regulated release capability is of great significance to achieve the precisely controlled release of pesticides. A preliminary bioassay against plutella xylostella revealed that 0.68μm LC-loaded microcapsules with good UV and thermal stability exhibited an activity similar to a commercial microcapsule formulation. These results demonstrated such an aqueous microcapsule delivery system had a great potential to be further explored for developing an effective and environmentally friendly pesticide-release formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-06-26

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

Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery.

PubMed

Song, Hyun Beom; Lee, Kang Ju; Seo, Il Ho; Lee, Ji Yong; Lee, Sang-Mok; Kim, Jin Hyoung; Kim, Jeong Hun; Ryu, WonHyoung

2015-07-10

It has been challenging for microneedles to deliver drugs effectively to thin tissues with little background support such as the cornea. Herein, we designed a microneedle pen system, a single microneedle with a spring-loaded microneedle applicator to provide impact insertion. To firmly attach solid microneedles with 140 μm in height at the end of macro-scale applicators, a transfer molding process was employed. The fabricated microneedle pens were then applied to mouse corneas. The microneedle pens successfully delivered rhodamine dye deep enough to reach the stromal layer of the cornea with small entry only about 1000 μm(2). When compared with syringes or 30 G needle tips, microneedle pens could achieve more localized and minimally invasive delivery without any chances of perforation. To investigate the efficacy of microneedle pens as a way of drug delivery, sunitinib malate proven to inhibit in vitro angiogenesis, was delivered to suture-induced angiogenesis model. When compared with delivery by a 30 G needle tip dipped with sunitinib malate, only delivery by microneedle pens could effectively inhibit corneal neovascularization in vivo. Microneedle pens could effectively deliver drugs to thin tissues without impairing merits of using microneedles: localized and minimally invasive delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

[Surgical methods for delivery in modern obstetrics and their influence on maternal and infant health].

PubMed

Kokhanevych, Ie V; Mitsoda, R M; Konoplianko, T V; Konoplianko, V V

2000-03-01

The article addresses issues of comparative characterization of deliveries involving surgery and impact thereof on the health of the mother and her child. Risk factors are identified that the mother and her child run in sectio cesarea, in application of obstetrical forceps, and in vacuum-extraction of the fetus. Cesarean section was found out to be the most acceptable mode of delivery in origination of organic and functional nervous system involvement in children but the most ill-chosen and unpropitious one in the mother, especially so in those groups at risk for bleeding, septic complications, and genital endometriosis. Among those surgical methods of delivery being the least traumatic to the mother are obstetrical forceps and vacuum-extraction of the fetus.

Methods for engaging stakeholders in comparative effectiveness research: a patient-centered approach to improving diabetes care.

PubMed

Schmittdiel, Julie A; Desai, Jay; Schroeder, Emily B; Paolino, Andrea R; Nichols, Gregory A; Lawrence, Jean M; O'Connor, Patrick J; Ohnsorg, Kris A; Newton, Katherine M; Steiner, John F

2015-06-01

Engaging stakeholders in the research process has the potential to improve quality of care and the patient care experience. Online patient community surveys can elicit important topic areas for comparative effectiveness research. Stakeholder meetings with substantial patient representation, as well as representation from health care delivery systems and research funding agencies, are a valuable tool for selecting and refining pilot research and quality improvement projects. Giving patient stakeholders a deciding vote in selecting pilot research topics helps ensure their 'voice' is heard. Researchers and health care leaders should continue to develop best-practices and strategies for increasing patient involvement in comparative effectiveness and delivery science research.

Preliminary pharmacology of galactosylated chitosan/5-fluorouracil nanoparticles and its inhibition of hepatocellular carcinoma in mice

PubMed Central

Cheng, Mingrong; Liu, Zheng; Wan, Tao; He, Bing; Zha, Bingbing; Han, Jiang; Chen, Houxiang; Yang, Fengxiao; Li, Qing; Wang, Wei; Xu, Hongzhi; Ye, Tao

2012-01-01

Biodegradable polymer nanoparticle drug delivery systems are characterized by targeted drug delivery, improved pharmacokinetic and biodistribution, enhanced drug stability and lowered side effects; these drug delivery systems are widely used for delivery of cytotoxic agents. The galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticle is a nanomaterial made by coupling GC, a polymer known to have the advantages described above, and 5-FU. The GC/5-FU nanoparticle is a sustained release system, it was showed that the peak time, half-life time, mean residence time (MRT) and area of under curve (AUC) of GC/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. The distribution of GC/5-FU in vivo revealed the greatest accumulation in the hepatic cancer tissues, and the hepatic cell was the target of the nanoparticles. Toxicology research showed that the toxicity of GC-5-FU was lower than that of 5-FU in mice. In vivo experiments showed that GC/5-FU can significantly inhibit tumor growth in an orthotropic liver cancer mouse model. GC/5-FU treatment can significantly lower the tumor weight and increase the survival time of mice when compared with 5-FU treatment alone. Flow cytometry and the TUNEL assay revealed that compared with 5-FU, GC/5-FU caused higher rates of G0-G1 arrest and apoptosis in hepatic cancer cells. PMID:22954702

Reducible, Dibromomaleimide-linked Polymers for Gene Delivery

PubMed Central

Tan, James-Kevin Y.; Choi, Jennifer L.; Wei, Hua; Schellinger, Joan G.; Pun, Suzie H.

2014-01-01

Polycations have been successfully used as gene transfer vehicles both in vitro and in vivo; however, their cytotoxicity has been associated with increasing molecular weight. Polymers that can be rapidly degraded after internalization are typically better tolerated by mammalian cells compared to their non-degradable counterparts. Here, we report the use of a dibromomaleimide-alkyne (DBM-alkyne) linking agent to reversibly bridge cationic polymer segments for gene delivery and to provide site-specific functionalization by azidealkyne cycloaddition chemistry. A panel of reducible and non-reducible, statistical copolymers of (2-dimethylamino) ethyl methacrylate (DMAEMA) and oligo(ethylene glycol) methyl ether methacrylate (OEGMA) were synthesized and evaluated. When complexed with plasmid DNA, the reducible and non-reducible polymers had comparable DNA condensation properties, sizes, and transfection efficiencies. When comparing cytotoxicity, the DBM-linked, reducible polymers were significantly less toxic than the non-reducible polymers. To demonstrate polymer functionalization by click chemistry, the DBM-linked polymers were tagged with an azidefluorophore and were used to monitor cellular uptake. Overall, this polymer system introduces the use of a reversible linker, DBM-alkyne, to the area of gene delivery and allows for facile, orthogonal, and site-specific functionalization of gene delivery vehicles. PMID:26214195

Selective gene silencing by viral delivery of short hairpin RNA

PubMed Central

2010-01-01

RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells. PMID:20858246

Comparative permeability studies with radioactive and nonradioactive risedronate sodium from self-microemulsifying drug delivery system and solution.

PubMed

Ilem-Ozdemir, Derya; Gundogdu, Evren; Ekinci, Meliha; Ozgenc, Emre; Asikoglu, Makbule

2015-01-01

The purpose of this work is to prepare a self-microemulsifying drug delivery system (SMEDDS) for risedronate sodium (RSD) and to compare the permeability with RSD solution. The solubility of RSD was determined in different vehicles. Phase diagrams were constructed to determine the optimum concentration of oil, surfactant, and cosurfactant. RSD SMEDDS was prepared by using a mixture of soybean oil, cremophor EL, span 80, and transcutol (2.02:7.72:23.27:61.74, w/w, respectively). The prepared RSD SMEDDS was characterized by droplet size value. In vitro Caco-2 cell permeability studies were performed for SMEDDS and solution of radioactive ((99 m)Tc-labeled RSD) and nonradioactive RSD. The experimental results indicated that RSD SMEDDS has good stability and its droplet size is between 216.68 ± 3.79 and 225.26 ± 7.65 during stability time. In addition, RSD SMEDDS has higher permeability value than the RSD solution for both radioactive and nonradioactive experiments. The results illustrated the potential use of SMEDDS for delivery of poorly absorbed RSD.

Evaluation of pharmacokinetic and pharmacodynamic profiles of liposomes for the cell type-specific delivery of small molecule drugs.

PubMed

Dasa, Siva Sai Krishna; Suzuki, Ryo; Mugler, Emily; Chen, Lanlin; Jansson-Löfmark, Rasmus; Michaëlsson, Erik; Lindfors, Lennart; Klibanov, Alexander L; French, Brent A; Kelly, Kimberly A

2017-11-01

Liposome-based drug formulations represent an exciting avenue of research as they increase efficacy to toxicity ratios. Current formulations rely on passive accumulation to the disease site where drug is taken up by the cells. Ligand mediated targeting increases the net accumulation of liposomes, however, an unexplored benefit is to potentially refine pharmacodynamics (PD) of a drug specifically to different cell types within diseased tissue. As a model system, we engineered cardiomyocyte- (I-1) and endothelial-targeted (B-40) liposomes to carry a VEGFR2 inhibitor (PTK787), and examined the effect of cell type-specific delivery on both pharmacokinetics (PK) and PD. Neovascularization in post-myocardial infarction was significantly reduced by B-40 liposomes loaded with PTK787 as compared to animals injected with I-1 liposomes, and profoundly more as compared to free PTK787. This study thus shows that the intraorgan targeting of drugs through cell type-specific delivery holds substantial promise towards lowering the minimal efficacious dose administered systemically. Published by Elsevier Inc.

Recommendations for routine reporting on indications for cesarean delivery in developing countries.

PubMed

Stanton, Cynthia; Ronsmans, Carine

2008-09-01

Cesarean delivery rates are increasing rapidly in many developing countries, particularly among wealthy women. Poor women have lower rates, often so low that they do not reach the minimum rate of 1 percent. Little data are available on clinical indications for cesarean section, information that could assist in understanding why cesarean delivery rates have changed. This paper presents recommendations for routine reporting on indications for cesarean delivery in developing countries. These recommendations resulted from an international consultation of researchers held in February 2006 to promote the collection of comparable data to understand change in, or composition of, the cesarean delivery rate in developing countries. Data are presented from selected countries, categorizing cesareans by three classification systems. A single classification system was recommended for use in both high and low cesarean delivery rate settings, given that underuse and overuse of cesarean section are evident within many populations. The group recommended a hierarchical categorization, prioritizing cesareans performed for absolute maternal indications. Categorization among the remaining nonabsolute indications is based on the primary indication for the procedure and include maternal and fetal indications and psychosocial indications, required for high cesarean delivery rate settings. Data on indications for cesarean sections are available everywhere the procedure is performed. All that is required is compilation and review at facility and at higher levels. Advocacy within ministries of health and medical professional organizations is required to advance these recommendations since researchers have inadequately communicated the health effects of both underuse and overuse of cesarean delivery.

SU-E-T-453: A Novel Daily QA System for Robotic Image Guided Radiosurgery with Variable Aperture Collimator

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

Wang, L; Nelson, B

Purpose: A novel end-to-end system using a CCD camera and a scintillator based phantom that is capable of measuring the beam-by-beam delivery accuracy of Robotic Radiosurgery has been developed and reported in our previous work. This work investigates its application to end-to-end type daily QA for Robotic Radiosurgery (Cyberknife) with Variable Aperture Collimator (Iris). Methods: The phantom was first scanned with a CT scanner at 0.625 slice thickness and exported to the Cyberknife Muliplan (v4.6) treatment planning system. An isocentric treatment plan was created consisting of ten beams of 25 Monitor Units each using Iris apertures of 7.5, 10, 15,more » 20, and 25 mm. The plan was delivered six times in two days on the Cyberknife G4 system with fiducial tracking on the four metal fiducials embedded in phantom with re-positioning between the measurements. The beam vectors (X, Y, Z) are measured and compared with the plan from the machine delivery file (XML file). The Iris apertures (FWHM) were measured from the beam flux map and compared with the commissioning data. Results: The average beam positioning accuracies of the six deliveries are 0.71 ± 0.40 mm, 0.72 ± 0.44 mm, 0.74 ± 0.42 mm, 0.70 ± 0.40 mm, 0.79 ± 0.44 mm and 0.69 ± 0.41 mm respectively. Radiation beam width (FWHM) variations are within ±0.05 mm, and they agree with the commissioning data within 0.22 mm. The delivery time for the plan is about 7 minutes and the results are given instantly. Conclusion: The experimental results agree with stated sub-millimeter delivery accuracy of Cyberknife system. Beam FWHM variations comply with the 0.2 mm accuracy of the Iris collimator at SAD. The XRV-100 system has proven to be a powerful tool in performing end-to-end type tests for Robotic Image Guided Radiosurgery Daily QA.« less

NanoClusters Enhance Drug Delivery in Mechanical Ventilation

NASA Astrophysics Data System (ADS)

Pornputtapitak, Warangkana

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

Flying-qualities criteria for wings-level-turn maneuvering during an air-to-ground weapon delivery task

NASA Technical Reports Server (NTRS)

Sammonds, R. I.; Bunnell, J. W., Jr.

1980-01-01

A moving-base simulator experiment conducted at Ames Research Center demonstrated that a wings-level-turn control mode improved flying qualities for air-to-ground weapons delivery compared with those of a conventional aircraft. Evaluations of criteria for dynamic response for this system have shown that pilot ratings correlate well on the basis of equivalent time constant of the initial response. Ranges of this time constant, as well as digital-system transport delays and lateral-acceleration control authorities that encompassed Level I through Level III handling qualities, were determined.

The impact of health plan delivery system organization on clinical quality and patient satisfaction.

PubMed

Gillies, Robin R; Chenok, Kate Eresian; Shortell, Stephen M; Pawlson, Gregory; Wimbush, Julian J

2006-08-01

The purpose of this study was to examine the extent to which measures of health plan clinical performance and measures of patient perceptions of care are associated with health plan organizational characteristics, including the percentage of care provided based on a group or staff model delivery system, for-profit (tax) status, and affiliation with a national managed care firm. Data describing health plans on region, age of health plan, for-profit status, affiliation with a national managed care firm, percentage of Medicare business, total enrollment, ratio of primary care physicians to specialists, HMO penetration, and form of health care delivery system (e.g., IPA, network, mixed, staff, group) were obtained from InterStudy. Clinical performance measures for women's health screening rates, child and adolescent immunization rates, heart disease screening rates, diabetes screening rates, and smoking cessation were developed from HEDIS data. Measures of patient perceptions of care are obtained from CAHPS survey data submitted as Healthplan Employer Data and Information Set, Consumer Assessment of Health Plans 2.0 H. Multivariate regression cross-sectional analysis of 272 health plans was used to evaluate the relationship of health plan characteristics with measures of clinical performance and patient perceptions of care. The form of delivery system, measured by percent of care delivered by staff and group model systems, is significantly related (p < or = .05) with four of the five clinical performance indices but none of the three satisfaction performance indices. Other variables significantly associated with performance were being geographically located in the Northeast, having nonprofit status, and for patient satisfaction, not being part of a larger insurance company. These comparative results provide evidence suggesting that the type of delivery system used by health plans is related to many clinical performance measures but is not related to patient perceptions of care. These findings underscore the importance of the form of the delivery system and the need for further inquiry that examines the relationship between organizational form and performance.

Ligand-conjugated mesoporous silica nanorattles based on enzyme targeted prodrug delivery system for effective lung cancer therapy

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

Sundarraj, Shenbagamoorthy, E-mail: sundarrajbu09@gmail.com; Thangam, Ramar; Department of Virology, King Institute of Preventive Medicine and Research, Guindy, Chennai 600 032, TN

2014-03-15

Epidermal growth factor receptor antibody (EGFRAb) conjugated silica nanorattles (SNs) were synthesized and used to develop receptor mediated endocytosis for targeted drug delivery strategies for cancer therapy. The present study determined that the rate of internalization of silica nanorattles was found to be high in lung cancer cells when compared with the normal lung cells. EGFRAb can specifically bind to EGFR, a receptor that is highly expressed in lung cancer cells, but is expressed at low levels in other normal cells. Furthermore, in vitro studies clearly substantiated that the cPLA{sub 2}α activity, arachidonic acid release and cell proliferation were considerablymore » reduced by pyrrolidine-2 loaded EGFRAb-SN in H460 cells. The cytotoxicity, cell cycle arrest and apoptosis were significantly induced by the treatment of pyrrolidine-2 loaded EGFRAb-SN when compared with free pyrrolidine-2 and pyrrolidine-2 loaded SNs in human non-small cell lung cancer cells. An in vivo toxicity assessment showed that silica nanorattles and EGFRAb-SN-pyrrolidine-2 exhibited low systemic toxicity in healthy Balb/c mice. The EGFRAb-SN-pyrrolidine-2 showed a much better antitumor activity (38%) with enhanced tumor inhibition rate than the pyrrolidine-2 on the non-small cell lung carcinoma subcutaneous model. Thus, the present findings validated the low toxicity and high therapeutic potentials of EGFRAb-SN-pyrrolidine-2, which may provide a convincing evidence of the silica nanorattles as new potential carriers for targeted drug delivery systems. - Highlights: • EGFRAb-SN developed for receptor-mediated Drug delivery system (DDS). • EGFRAb-SN-pyrrolidine-2 targeted DDS for cPLA2α inhibition in NSLC. • Study indicates EGFRAb-SN-pyrrolidine-2 as an efficient in target dug delivery carrier. • Study explains entire efficiency of EGFRAb-SN-pyrrolidine-2 in vitro and in vivo models.« less

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

PubMed

Sharma, Anupriya; Ramesh, Amitha; Thomas, Biju

2009-09-01

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

78 FR 30319 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

... Committee: Bioengineering Sciences & Technologies Integrated Review Group; Gene and Drug Delivery Systems..., [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.306, Comparative Medicine...

High-precision piezo-ejection ocular microdosing: Phase II study on local and systemic effects of topical phenylephrine.

PubMed

Ianchulev, Tsontcho; Weinreb, Robert; Tsai, James C; Lin, Shan; Pasquale, Louis R

2018-01-01

Conventional eyedropper-delivered volumes (25-50 µl) exceed the eye's usual tear-film volume (7 µl) and precorneal reservoir capacity, risking overflow and ocular/systemic complications. Piezoelectric high-precision microdosing may circumvent these limitations. Results & methodology: In this masked, nonrandomized, cross-over study, subjects (n = 12) underwent pupil dilation with topical phenylephrine (PE) administered by 32-µl eyedropper (2.5% or 10% formulation) and 8-µl electronic microdosing (10% formulation). Microdosing with PE-10% achieved comparable peak dilation as 10% eyedropper-delivery and superior dilation to 2.5% eyedropper-delivery (p = 0.009) at 75 min. Microdosing significantly reduced 20-min plasma PE levels versus PE10% eyedropper; neither treatment altered heart rate/blood pressure. Eye irritation occurred significantly less frequently with microdosing than PE10% eyedrops. Piezo-ejection PE microdosing achieves comparable biological effect as eyedropper dosing; reduced systemic absorption may decrease risk of systemic side effects.

Comparison of standard (self-directed) versus intensive patient training for the human insulin inhalation powder (HIIP) delivery system in patients with type 2 diabetes: efficacy, safety, and training measures.

PubMed

Rosenstock, Julio; Nakano, Masako; Silverman, Bernard L; Sun, Bin; de la Peña, Amparo; Suri, Ajit; Muchmore, Douglas B

2007-02-01

The Lilly/Alkermes human insulin inhalation powder (HIIP) delivery system [AIR (a registered trademark of Alkermes, Inc., Cambridge, MA) Inhaled Insulin System] was designed to be easy to use. Training methods were compared in insulin-naive patients with type 2 diabetes. Patients (n = 102) were randomized to standard or intensive training. With standard training, patients learned how to use the HIIP delivery system by reading directions for use (DFU) and trying on their own. Intensive training included orientation to the HIIP delivery system with individual coaching and inspiratory flow rate training. Both groups received preprandial HIIP + metformin with or without a thiazolidinedione for 4 weeks. Overall 2-h postprandial blood glucose (PPBG) excursion was the primary measure. Noninferiority was defined as the upper limit of the two-sided 95% confidence interval of the mean difference between groups being 1.2 < or = mmol/L. Overall 2-h PPBG excursions (least squares mean +/- SE) at endpoint were -0.11 +/- 0.38 (standard training) and 0.23 +/- 0.36 (intensive training) mmol/L. The mean difference (standard minus intensive training) and two-sided 95% confidence interval were -0.35 (-1.02, 0.33) mmol/L. No statistically or clinically significant differences were observed between training methods in premeal, postmeal, or bedtime blood glucose values, HIIP doses at endpoint, or blood glucose values after a test meal. No discontinuations occurred because of difficulty of use or dislike of the HIIP system. DFU compliance was >90% in both training groups. There were no significant differences between training methods in safety measures. The HIIP delivery system is easy to use, and most patients can learn to use it by reading the DFU without assistance from health care professionals.

Preparation and evaluation of a phospholipid-based injectable gel for the long term delivery of leuprolide acetaterrh.

PubMed

Long, Danhong; Gong, Tao; Zhang, Zhirong; Ding, Rui; Fu, Yao

2016-07-01

A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-a-month injection of LA-loaded SPME (SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.

Changes in Quality of Health Care Delivery after Vertical Integration.

PubMed

Carlin, Caroline S; Dowd, Bryan; Feldman, Roger

2015-08-01

To fill an empirical gap in the literature by examining changes in quality of care measures occurring when multispecialty clinic systems were acquired by hospital-owned, vertically integrated health care delivery systems in the Twin Cities area. Administrative data for health plan enrollees attributed to treatment and control clinic systems, merged with U.S. Census data. We compared changes in quality measures for health plan enrollees in the acquired clinics to enrollees in nine control groups using a differences-in-differences model. Our dataset spans 2 years prior to and 4 years after the acquisitions. We estimated probit models with errors clustered within enrollees. Data were assembled by the health plan's informatics team. Vertical integration is associated with increased rates of colorectal and cervical cancer screening and more appropriate emergency department use. The probability of ambulatory care-sensitive admissions increased when the acquisition caused disruption in admitting patterns. Moving a clinic system into a vertically integrated delivery system resulted in limited increases in quality of care indicators. Caution is warranted when the acquisition causes disruption in referral patterns. © Health Research and Educational Trust.

Quantitative measurement of delivery and gene silencing activities of siRNA polyplexes containing pyridylthiourea-grafted polyethylenimines.

PubMed

Pinel, Sophie; Aman, Emmanuel; Erblang, Felix; Dietrich, Jonathan; Frisch, Benoit; Sirman, Julien; Kichler, Antoine; Sibler, Annie-Paule; Dontenwill, Monique; Schaffner, Florence; Zuber, Guy

2014-05-28

The activity of synthetic interfering nucleic acids (siRNAs) relies on the capacity of delivery systems to efficiently transport nucleic acids into the cytosol of target cells. The pyridylthiourea-grafted 25KDa polyethylenimine (πPEI) is an excellent carrier for siRNA delivery into cells and it was extensively investigated in this report. Quantification of the siRNA-mediated gene silencing efficiency indicated that the πPEI specific delivery activity at the cell level may be measured and appears relatively constant in various cell lines. Delivery experiments assaying inhibitors of various entry pathways or concanamycin A, an inhibitor of the H(+)/ATPase vacuolar pump showed that the πPEI/siRNA polyplexes did not require any specific entry mode but strongly relied on vacuolar acidification for functional siRNA delivery. Next, πPEI polyplexes containing a siRNA targeting the transcription factor HIF-1α, known to be involved in tumor progression, were locally injected into mice xenografted with a human glioblastoma. A 55% reduction of the level of the target mRNA was observed at doses comparable to those used in vitro when the πPEI delivery activity was calculated per cell. Altogether, our study underscores the usefulness of "simple"/rough cationic polymers for siRNA delivery despite their intrinsic limitations. The study underscores as well as that bottom-up strategies make sense. The in vitro experiments can precede in vivo administration and be of high value for selection of the carrier with enhanced specific delivery activity and parallel other research aiming at improving synthetic delivery systems for resilience in the blood and for enhanced tissue-targeting capacity. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Ellefson, S; Department of Human Oncology, University of Wisconsin, Madison, WI; Culberson, W

Purpose: Discrepancies in absolute dose values have been detected between the ViewRay treatment planning system and ArcCHECK readings when performing delivery quality assurance on the ViewRay system with the ArcCHECK-MR diode array (SunNuclear Corporation). In this work, we investigate whether these discrepancies are due to errors in the ViewRay planning and/or delivery system or due to errors in the ArcCHECK’s readings. Methods: Gamma analysis was performed on 19 ViewRay patient plans using the ArcCHECK. Frequency analysis on the dose differences was performed. To investigate whether discrepancies were due to measurement or delivery error, 10 diodes in low-gradient dose regions weremore » chosen to compare with ion chamber measurements in a PMMA phantom with the same size and shape as the ArcCHECK, provided by SunNuclear. The diodes chosen all had significant discrepancies in absolute dose values compared to the ViewRay TPS. Absolute doses to PMMA were compared between the ViewRay TPS calculations, ArcCHECK measurements, and measurements in the PMMA phantom. Results: Three of the 19 patient plans had 3%/3mm gamma passing rates less than 95%, and ten of the 19 plans had 2%/2mm passing rates less than 95%. Frequency analysis implied a non-random error process. Out of the 10 diode locations measured, ion chamber measurements were all within 2.2% error relative to the TPS and had a mean error of 1.2%. ArcCHECK measurements ranged from 4.5% to over 15% error relative to the TPS and had a mean error of 8.0%. Conclusion: The ArcCHECK performs well for quality assurance on the ViewRay under most circumstances. However, under certain conditions the absolute dose readings are significantly higher compared to the planned doses. As the ion chamber measurements consistently agree with the TPS, it can be concluded that the discrepancies are due to ArcCHECK measurement error and not TPS or delivery system error. This work was funded by the Bhudatt Paliwal Professorship and the University of Wisconsin Medical Radiation Research Center.« less

Drug delivery technologies for autoimmune disease.

PubMed

Phillips, Brett E; Giannoukakis, Nick

2010-11-01

Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome. Herein, the range of drug delivery methods available and under development and how they can be useful to treat autoimmune diseases are discussed. Polymer delivery methods, as well as biological methods that include fusion proteins, targeted antibodies, recombinant viruses and cell products are compared. Readers will gain insight into the progression of clinical trials for different technologies and drug delivery methods useful for targeting and modulating the function of autoreactive immune cells. Several tissue-specific polymer-based and biologic drug delivery systems are now in Phase II/III clinical trials. Although these trials are focused mainly on cancer treatment, lessons from these trials can guide the use of the same agents for autoimmunity therapeutics.

Cesarean Section Rate in Singleton Primiparae and Related Factors in Beijing, China

PubMed Central

Song, Geng; Wei, Yu-Mei; Zhu, Wei-Wei; Yang, Hui-Xia

2017-01-01

Background: The cesarean section rate (CSR) has been a main concern worldwide. The present study aimed to investigate the CSR in Beijing, China, and to analyze the related factors of CS delivery. Methods: An observational study was conducted in 15 medical centers in Beijing using a systemic cluster sampling method. In total, 15,194 pregnancies were enrolled in the study between June 20, 2013 and November 30, 2013. Independent t-tests and Pearson's Chi-square test were used to examine differences between two groups, and related factors of the CSR were examined by multivariable logistic regression. Results: The CSR was 41.9% (4471/10,671) in singleton primiparae. Women who were more than 35 years old had a 7.4-fold increased risk of CS delivery compared with women <25 years old (odd ratio [OR] = 7.388, 95% confidence interval [CI] = 5.561–9.816, P < 0.001). Prepregnancy obese women had a 2-fold increased risk of CS delivery compared with prepregnancy normal weight women (OR = 2.058, 95% CI = 1.640–2.584, P < 0.001). The excessive weight gain group had a 1.4-fold increased risk of CS delivery compared with the adequate weight gain group (OR = 1.422, 95% CI = 1.289–1.568, P < 0.001). Gestational diabetes mellitus (GDM) women and DM women had an increased risk of CS delivery (1.2- and 1.7-fold, respectively) compared with normal blood glucose women. Women who were born in rural areas had a lower risk of CS delivery than did those who were born in urban areas (OR = 0.696, 95% CI = 0.625–0.775, P < 0.001). The risk of CS delivery gradually increased with a decreasing education level. Neonates weighing 3000–3499 g had the lowest CSR (36.2%). Neonates weighing <2500 g had a 2-fold increased risk of CS delivery compared with neonates weighing 3000–3499 g (OR = 2.020, 95% CI = 1.537–2.656, P < 0.001). Neonates weighing ≥4500 g had an 8.3-fold increased risk of CS delivery compared with neonates weighing 3000–3499 g (OR = 8.313, 95% CI = 4.436–15.579, P < 0.001). Conclusions: Maternal age, prepregnancy body mass index, gestational weight gain, blood glucose levels, residence, education level, and singleton fetal birth weight are all factors that might significantly affect the CSR. PMID:29052558

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.

Diabetes care and outcomes for American Indians and Alaska natives in commercial integrated delivery systems: a SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) Study.

PubMed

Schmittdiel, Julie A; Steiner, John F; Adams, Alyce S; Dyer, Wendy; Beals, Janette; Henderson, William G; Desai, Jay; Morales, Leo S; Nichols, Gregory A; Lawrence, Jean M; Waitzfelder, Beth; Butler, Melissa G; Pathak, Ram D; Hamman, Richard F; Manson, Spero M

2014-01-01

To compare cardiovascular disease risk factor testing rates and intermediate outcomes of care between American Indian/Alaska Native (AI/AN) patients with diabetes and non-Hispanic Caucasians enrolled in nine commercial integrated delivery systems in the USA. We used modified Poisson regression models to compare the annual testing rates and risk factor control levels for glycated haemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP); number of unique diabetes drug classes; insulin use; and oral diabetes drug medication adherence between insured AI/AN and non-Hispanic white adults with diabetes aged ≥18 in 2011. 5831 AI/AN patients (1.8% of the cohort) met inclusion criteria. After adjusting for age, gender, comorbidities, insulin use, and geocoded socioeconomic status, AI/AN patients had similar rates of annual HbA1c, LDL-C, and SBP testing, and LDL-C and SBP control, compared with non-Hispanic Caucasians. However, AI/AN patients were significantly more likely to have HbA1c >9% (>74.9 mmol/mol; RR=1.47, 95% CI 1.38 to 1.58), and significantly less likely to adhere to their oral diabetes medications (RR=0.90, 95% CI 0.88 to 0.93) compared with non-Hispanic Caucasians. AI/AN patients in commercial integrated delivery systems have similar blood pressure and cholesterol testing and control, but significantly lower rates of HbA1c control and diabetes medication adherence, compared with non-Hispanic Caucasians. As more AI/ANs move to urban and suburban settings, clinicians and health plans should focus on addressing disparities in diabetes care and outcomes in this population.

Diabetes care and outcomes for American Indians and Alaska natives in commercial integrated delivery systems: a SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) Study

PubMed Central

Schmittdiel, Julie A; Steiner, John F; Adams, Alyce S; Dyer, Wendy; Beals, Janette; Henderson, William G; Desai, Jay; Morales, Leo S; Nichols, Gregory A; Lawrence, Jean M; Waitzfelder, Beth; Butler, Melissa G; Pathak, Ram D; Hamman, Richard F; Manson, Spero M

2014-01-01

Objective To compare cardiovascular disease risk factor testing rates and intermediate outcomes of care between American Indian/Alaska Native (AI/AN) patients with diabetes and non-Hispanic Caucasians enrolled in nine commercial integrated delivery systems in the USA. Research design and methods We used modified Poisson regression models to compare the annual testing rates and risk factor control levels for glycated haemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP); number of unique diabetes drug classes; insulin use; and oral diabetes drug medication adherence between insured AI/AN and non-Hispanic white adults with diabetes aged ≥18 in 2011. Results 5831 AI/AN patients (1.8% of the cohort) met inclusion criteria. After adjusting for age, gender, comorbidities, insulin use, and geocoded socioeconomic status, AI/AN patients had similar rates of annual HbA1c, LDL-C, and SBP testing, and LDL-C and SBP control, compared with non-Hispanic Caucasians. However, AI/AN patients were significantly more likely to have HbA1c >9% (>74.9 mmol/mol; RR=1.47, 95% CI 1.38 to 1.58), and significantly less likely to adhere to their oral diabetes medications (RR=0.90, 95% CI 0.88 to 0.93) compared with non-Hispanic Caucasians. Conclusions AI/AN patients in commercial integrated delivery systems have similar blood pressure and cholesterol testing and control, but significantly lower rates of HbA1c control and diabetes medication adherence, compared with non-Hispanic Caucasians. As more AI/ANs move to urban and suburban settings, clinicians and health plans should focus on addressing disparities in diabetes care and outcomes in this population. PMID:25452877

How to achieve optimal organization of primary care service delivery at system level: lessons from Europe.

PubMed

Pelone, Ferruccio; Kringos, Dionne S; Spreeuwenberg, Peter; De Belvis, Antonio G; Groenewegen, Peter P

2013-09-01

To measure the relative efficiency of primary care (PC) in turning their structures into services delivery and turning their services delivery into quality outcomes. Cross-sectional study based on the dataset of the Primary Healthcare Activity Monitor for Europe project. Two Data Envelopment models were run to compare the relative technical efficiency. A sensitivity analysis of the resulting efficiency scores was performed. PC systems in 22 European countries in 2009/2010. Model 1 included data on PC governance, workforce development and economic conditions as inputs and access, coordination, continuity and comprehensiveness of care as outputs. Model 2 included the previous process dimensions as inputs and quality indicators as outputs. There is relatively reasonable efficiency in all countries at delivering as many as possible PC processes at a given level of PC structure. It is particularly important to invest in economic conditions to achieve an efficient structure-process balance. Only five countries have fully efficient PC systems in turning their services delivery into high quality outcomes, using a similar combination of access, continuity and comprehensiveness, although they differ on the adoption of coordination of services. There is a large variation in efficiency levels obtained by countries with inefficient PC in turning their services delivery into quality outcomes. Maximizing the individual functions of PC without taking into account the coherence within the health-care system is not sufficient from a policymaker's point of view when aiming to achieve efficiency.

Clinical, biochemical, and hygiene assessment of stabled horses provided continuous or intermittent access to drinking water.

PubMed

Freeman, D A; Cymbaluk, N F; Schott, H C; Hinchcliff, K; McDonnell, S M; Kyle, B

1999-11-01

To compare health, hydration status, and management of stabled pregnant mares provided drinking water continuously or via 1 of 3 intermittent delivery systems. 22 Quarter Horse (QH) or QH-crossbred mares and 18 Belgian or Belgian-crossbred mares (study 1); 24 QH or QH-crossbred mares and 18 Belgian or Belgian-crossbred mares (study 2). Stabled horses were provided water continuously or via 1 of 3 intermittent water delivery systems in 2 study periods during a 2-year period. Body temperature, attitude, appetite, water intake, and urine output were recorded daily. Hygiene of each horse and the stable were assessed weekly. Clinical and biochemical measures of hydration were determined 3 times during each study. Clinical measures of hydration included skin turgor, gum moisture, capillary refill time, and fecal consistency. Biochemical measures of hydration included PCV, plasma total protein concentration, serum osmolality, plasma vasopressin concentration, urine specific gravity, and urine osmolality. All horses remained healthy. Stable hygiene was worse when horses had continuous access to water. Clinical and biochemical measures of hydration did not differ among water delivery systems. Various continuous and intermittent water delivery systems provided adequate amounts of water to stabled horses to maintain health and hydration status. Providing intermittent access to water may be preferable on the basis of stable hygiene.

Boosting facility deliveries with results-based financing: a mixed-methods evaluation of the government midwifery incentive scheme in Cambodia.

PubMed

Ir, Por; Korachais, Catherine; Chheng, Kannarath; Horemans, Dirk; Van Damme, Wim; Meessen, Bruno

2015-08-15

Increasing the coverage of skilled attendance at births in a health facility (facility delivery) is crucial for saving the lives of mothers and achieving Millennium Development Goal five. Cambodia has significantly increased the coverage of facility deliveries and reduced the maternal mortality ratio in the last decade. The introduction of a nationwide government implemented and funded results-based financing initiative, known as the Government Midwifery Incentive Scheme (GMIS), is considered one of the most important contributors to this. We evaluated GMIS to explore its effects on facility deliveries and the health system. We used a mixed-methods design. An interrupted time series model was applied, using routine longitudinal data on reported deliveries between 2006 and 2011 that were extracted from the health information system. In addition, we interviewed 56 key informants and performed 12 focus group discussions with 124 women who had given birth (once or more) since 2006. Findings from the quantitative data were carefully interpreted and triangulated with those from qualitative data. We found that facility deliveries have tripled from 19% of the estimated number of births in 2006 to 57% in 2011 and this increase was more substantial at health centres as compared to hospitals. Segmented linear regressions showed that the introduction of GMIS in October 2007 made the increase in facility deliveries and deliveries with skilled attendants significantly jump by 18 and 10% respectively. Results from qualitative data also suggest that the introduction of GMIS together with other interventions that aimed to improve access to essential maternal health services led to considerable improvements in public health facilities and a steep increase in facility deliveries. Home deliveries attended by traditional birth attendants decreased concomitantly. We also outline several operational issues and limitations of GMIS. The available evidence strongly suggests that GMIS is an effective mechanism to complement other interventions to improve health system performance and boost facility deliveries as well as skilled birth attendance; thereby contributing to the reduction of maternal mortality. Our findings provide useful lessons for Cambodia to further improve GMIS and for other low-income countries to implement similar results-based financing mechanisms.

Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake

PubMed Central

Cho, Hyun-Jong; Park, Jin Woo; Yoon, In-Soo; Kim, Dae-Duk

2014-01-01

Docetaxel is a potent anticancer drug, but development of an oral formulation has been hindered mainly due to its poor oral bioavailability. In this study, solid lipid nanoparticles (SLNs) surface-modified by Tween 80 or D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) were prepared and evaluated in terms of their feasibility as oral delivery systems for docetaxel. Tween 80-emulsified and TPGS 1000-emulsified tristearin-based lipidic nanoparticles were prepared by a solvent-diffusion method, and their particle size distribution, zeta potential, drug loading, and particle morphology were characterized. An in vitro release study showed a sustained-release profile of docetaxel from the SLNs compared with an intravenous docetaxel formulation (Taxotere®). Tween 80-emulsified SLNs showed enhanced intestinal absorption, lymphatic uptake, and relative oral bioavailability of docetaxel compared with Taxotere in rats. These results may be attributable to the absorption-enhancing effects of the tristearin nanoparticle. Moreover, compared with Tween 80-emulsified SLNs, the intestinal absorption and relative oral bioavailability of docetaxel in rats were further improved in TPGS 1000-emulsified SLNs, probably due to better inhibition of drug efflux by TPGS 1000, along with intestinal lymphatic uptake. Taken together, it is worth noting that these surface-modified SLNs may serve as efficient oral delivery systems for docetaxel. PMID:24531717

Microbubble-assisted p53, RB, and p130 gene transfer in combination with radiation therapy in prostate cancer.

PubMed

Nande, Rounak; Greco, Adelaide; Gossman, Michael S; Lopez, Jeffrey P; Claudio, Luigi; Salvatore, Marco; Brunetti, Arturo; Denvir, James; Howard, Candace M; Claudio, Pier Paolo

2013-06-01

Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes. Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.

Potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against tuberculosis: A systematic review.

PubMed

Khademi, Farzad; Derakhshan, Mohammad; Yousefi-Avarvand, Arshid; Tafaghodi, Mohsen

2018-02-01

Production of effective tuberculosis (TB) vaccine is necessity. However, the development of new subunit vaccines is faced with concerns about their weak immunogenicity. To overcome such problems, polymers-based vaccine delivery systems have been proposed to be used via various routes. The purpose of this study was to determine the potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against TB. PubMed, Scopus, Science-Direct, and the ISI web of knowledge databases were searched for related keywords. A total of 420 articles, written up to June 25, 2016, were collected on the potential of polymeric particles as TB vaccine delivery systems after parenteral and non-parenteral immunization. Thirty-one relevant articles were selected by applying inclusion and exclusion criteria. It was shown that the immunogenicity of TB vaccines had been improved by using biodegradable and non-biodegradable synthetic polymers as well as natural polymers and they are better able to enhance the humoral and cellular immune responses, compared to TB vaccines alone. The present study revealed that various polymeric particles, after M. tuberculosis challenge in animal models, provide long-lasting protection against TB. PLGA (poly (lactide-co-glycolide)) and chitosan polymers were widely used as TB vaccine delivery systems/adjuvants. It seems that PLGA and chitosan polymers are well-suited particles for the parenteral and non-parenteral administration of TB vaccines, respectively. Non-biodegradable synthetic polymers in comparison with biodegradable synthetic and natural polymers have been used less frequently. Therefore, further study on this category of polymers is required.

Latent cytokines for targeted therapy of inflammatory disorders.

PubMed

Mullen, Lisa; Adams, Gill; Layward, Lorna; Vessillier, Sandrine; Annenkov, Alex; Mittal, Gayatri; Rigby, Anne; Sclanders, Michelle; Baker, David; Gould, David; Chernajovsky, Yuti

2014-01-01

The use of cytokines as therapeutic agents is important, given their potent biological effects. However, this very potency, coupled with the pleiotropic nature and short half-life of these molecules, has limited their therapeutic use. Strategies to increase the half-life and to decrease toxicity are necessary to allow effective treatment with these molecules. A number of strategies are used to overcome the natural limitations of cytokines, including PEGylation, encapsulation in liposomes, fusion to targeting peptides or antibodies and latent cytokines. Latent cytokines are engineered using the latency-associated peptide of transforming growth factor-β to produce therapeutic cytokines/peptides that are released only at the site of disease by cleavage with disease-induced matrix metalloproteinases. The principles underlying the latent cytokine technology are described and are compared to other methods of cytokine delivery. The potential of this technology for developing novel therapeutic strategies for the treatment of diseases with an inflammatory-mediated component is discussed. Methods of therapeutic cytokine delivery are addressed. The latent cytokine technology holds significant advantages over other methods of drug delivery by providing simultaneously increased half-life and localised drug delivery without systemic effects. Cytokines that failed clinical trials should be reassessed using this delivery system.

The Preemptive Stocker Dispatching Rule of Automatic Material Handling System in 300 mm Semiconductor Manufacturing Factories

NASA Astrophysics Data System (ADS)

Wang, C. N.; Lin, H. S.; Hsu, H. P.; Wang, Yen-Hui; Chang, Y. P.

2016-04-01

The integrated circuit (IC) manufacturing industry is one of the biggest output industries in this century. The 300mm wafer fabs is the major fab size of this industry. The automatic material handling system (AMHS) has become one of the most concerned issues among semiconductor manufacturers. The major lot delivery of 300mm fabs is used overhead hoist transport (OHT). The traffic jams are happened frequently due to the wide variety of products and big amount of OHTs moving in the fabs. The purpose of this study is to enhance the delivery performance of automatic material handling and reduce the delay and waiting time of product transportation for both hot lots and normal lots. Therefore, this study proposes an effective OHT dispatching rule: preemptive stocker dispatching (PSD). Simulation experiments are conducted and one of the best differentiated preemptive rule, differentiated preemptive dispatching (DPD), is used for comparison. Compared with DPD, The results indicated that PSD rule can reduce average variable delivery time of normal lots by 13.15%, decreasing average variable delivery time of hot lots by 17.67%. Thus, the PSD rule can effectively reduce the delivery time and enhance productivity in 300 mm wafer fabs.

Oxygen delivery during cardiopulmonary bypass (and renal outcome) using two systems of extracorporeal circulation: a retrospective review.

PubMed

Bennett, Mark J; Rajakaruna, Cha; Bazerbashi, Samer; Webb, Gerry; Gomez-Cano, Mayam; Lloyd, Clinton

2013-06-01

To investigate the combined influence of blood flow and haemodilution with either a miniaturized (Mini-CPB) or a conventional cardiopulmonary bypass (C-CPB) circuit on average oxygen delivery during bypass. The influence of this on clinical outcome, particularly renal dysfunction after routine coronary artery bypass surgery (CABG), was measured. Retrospective analysis in two groups of 160 patients based on the surgeon's preference for bypass circuit. We compared consecutive patients undergoing isolated CABG surgery by two surgeons using Mini-CPB with a matched cohort of patients, from the same period, undergoing isolated CABG surgery by four other surgeons using a C-CPB. No trial-related intervention occurred. Data on bypass circuit parameters and clinical outcomes were acquired from routinely collected data sources. Average cardiopulmonary bypass pump flow was significantly lower with Mini-CPB compared with C-CPB. Mini-CPB resulted in significantly less haemodilution. The resultant calculated average oxygen delivery provided by the two systems was the same. Percentage change in plasma creatinine was significantly and inversely related to the oxygen delivery during CPB. There was no difference in percentage change in plasma creatinine between groups. The risk of having Acute Kidney Injury Network (AKIN) score ≥ 1 increased 1% for every 1 ml min(-1) m(-2) decrease in oxygen delivery (P = 0.0001, OR 0.990, 95% CI 0.984-0.995). Despite aiming for the same target pump flow, periodic limitations of venous return to the pump resulted in a significant reduction in average flow delivered to the patient by Mini-CPB. Less haemodilution compensated for this reduction, so that the average oxygen delivery was the same. The association between oxygen delivery and postoperative change in plasma creatinine was evident in both groups. Further work to understand whether there is a particular cohort of patients who benefit (or are put at risk) by one method of CPB vs the other is warranted.

Lapatinib nano-delivery systems: a promising future for breast cancer treatment.

PubMed

Bonde, Gunjan Vasant; Yadav, Sarita Kumari; Chauhan, Sheetal; Mittal, Pooja; Ajmal, Gufran; Thokala, Sathish; Mishra, Brahmeshwar

2018-05-01

Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation. Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose. Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.

Utilizing Health Information Technology to Support Universal Healthcare Delivery: Experience of a National Healthcare System.

PubMed

Syed-Abdul, Shabbir; Hsu, Min-Huei; Iqbal, Usman; Scholl, Jeremiah; Huang, Chih-Wei; Nguyen, Phung Anh; Lee, Peisan; García-Romero, Maria Teresa; Li, Yu-Chuan Jack; Jian, Wen-Shan

2015-09-01

Recent discussions have focused on using health information technology (HIT) to support goals related to universal healthcare delivery. These discussions have generally not reflected on the experience of countries with a large amount of experience using HIT to support universal healthcare on a national level. HIT was compared globally by using data from the Ministry of the Interior, Republic of China (Taiwan). Taiwan has been providing universal healthcare since 1995 and began to strategically implement HIT on a national level at that time. Today the national-level HIT system is more extensive in Taiwan than in many other countries and is used to aid administration, clinical care, and public health. The experience of Taiwan thus can provide an illustration of how HIT can be used to support universal healthcare delivery. In this article we present an overview of some key historical developments and successes in the adoption of HIT in Taiwan over a 17-year period, as well as some more recent developments. We use this experience to offer some strategic perspectives on how it can aid in the adoption of large-scale HIT systems and on how HIT can be used to support universal healthcare delivery.

Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery

PubMed Central

Mather, Laurence E; Woodhouse, Annie; Ward, M Elizabeth; Farr, Stephen J; Rubsamen, Reid A; Eltherington, Lorne G

1998-01-01

Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist™, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. Methods Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMist™ and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. Results Plasma concentrations from SmartMist™ were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. Conclusions Fentanyl delivery using SmartMist™ can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae. PMID:9690947

The role of complexity metrics in a multi-institutional dosimetry audit of VMAT

PubMed Central

Agnew, Christina E; Hussein, Mohammad; Tsang, Yatman; McWilliam, Alan; Hounsell, Alan R; Clark, Catharine H

2016-01-01

Objective: To demonstrate the benefit of complexity metrics such as the modulation complexity score (MCS) and monitor units (MUs) in multi-institutional audits of volumetric-modulated arc therapy (VMAT) delivery. Methods: 39 VMAT treatment plans were analysed using MCS and MU. A virtual phantom planning exercise was planned and independently measured using the PTW Octavius® phantom and seven29® 2D array (PTW-Freiburg GmbH, Freiburg, Germany). MCS and MU were compared with the median gamma index pass rates (2%/2 and 3%/3 mm) and plan quality. The treatment planning systems (TPS) were grouped by VMAT modelling being specifically designed for the linear accelerator manufacturer's own treatment delivery system (Type 1) or independent of vendor for VMAT delivery (Type 2). Differences in plan complexity (MCS and MU) between TPS types were compared. Results: For Varian® linear accelerators (Varian® Medical Systems, Inc., Palo Alto, CA), MCS and MU were significantly correlated with gamma pass rates. Type 2 TPS created poorer quality, more complex plans with significantly higher MUs and MCS than Type 1 TPS. Plan quality was significantly correlated with MU for Type 2 plans. A statistically significant correlation was observed between MU and MCS for all plans (R = −0.84, p < 0.01). Conclusion: MU and MCS have a role in assessing plan complexity in audits along with plan quality metrics. Plan complexity metrics give some indication of plan deliverability but should be analysed with plan quality. Advances in knowledge: Complexity metrics were investigated for a national rotational audit involving 34 institutions and they showed value. The metrics found that more complex plans were created for planning systems which were independent of vendor for VMAT delivery. PMID:26511276

The role of complexity metrics in a multi-institutional dosimetry audit of VMAT.

PubMed

McGarry, Conor K; Agnew, Christina E; Hussein, Mohammad; Tsang, Yatman; McWilliam, Alan; Hounsell, Alan R; Clark, Catharine H

2016-01-01

To demonstrate the benefit of complexity metrics such as the modulation complexity score (MCS) and monitor units (MUs) in multi-institutional audits of volumetric-modulated arc therapy (VMAT) delivery. 39 VMAT treatment plans were analysed using MCS and MU. A virtual phantom planning exercise was planned and independently measured using the PTW Octavius(®) phantom and seven29(®) 2D array (PTW-Freiburg GmbH, Freiburg, Germany). MCS and MU were compared with the median gamma index pass rates (2%/2 and 3%/3 mm) and plan quality. The treatment planning systems (TPS) were grouped by VMAT modelling being specifically designed for the linear accelerator manufacturer's own treatment delivery system (Type 1) or independent of vendor for VMAT delivery (Type 2). Differences in plan complexity (MCS and MU) between TPS types were compared. For Varian(®) linear accelerators (Varian(®) Medical Systems, Inc., Palo Alto, CA), MCS and MU were significantly correlated with gamma pass rates. Type 2 TPS created poorer quality, more complex plans with significantly higher MUs and MCS than Type 1 TPS. Plan quality was significantly correlated with MU for Type 2 plans. A statistically significant correlation was observed between MU and MCS for all plans (R = -0.84, p < 0.01). MU and MCS have a role in assessing plan complexity in audits along with plan quality metrics. Plan complexity metrics give some indication of plan deliverability but should be analysed with plan quality. Complexity metrics were investigated for a national rotational audit involving 34 institutions and they showed value. The metrics found that more complex plans were created for planning systems which were independent of vendor for VMAT delivery.

Microemulsion-loaded hydrogel formulation of butenafine hydrochloride for improved topical delivery.

PubMed

Pillai, Anilkumar B; Nair, Jyothilaksmi V; Gupta, Nishant Kumar; Gupta, Swati

2015-09-01

Topical microemulsion systems for the antifungal drug, butenafine hydrochloride (BTF) were designed and developed to overcome the problems associated with the cutaneous delivery due to poor water solubility. The solubility of BTF in oils, surfactants and co-surfactants was evaluated to screen the components of the microemulsion. Isopropyl palmitate was used as the oil phase, aerosol OT as the surfactant and sorbitan monooleate as co-surfactant. The pseudoternary diagrams were constructed to identify the area of microemulsion existence and optimum systems were designed. The systems were assessed for drug-loading efficiency and characterized for pH, robustness to dilution, globule size, drug content and stability. Viscosity analysis, spreadability, drug content assay, ex vivo skin permeation study and antifungal activity assay were performed for the optimized microemulsion-loaded hydrogel. The optimized BTF microemulsion had a small and uniform globule size. The incorporation of microemulsion system into Carbopol 940 gel was found to be better as compared to sodium alginate or hydroxyl propyl methyl cellulose (HPMC K4 M) gel. The developed gel has shown better ex vivo skin permeation and antifungal activity when compared to marketed BTF cream. Thus, the results provide a basis for the successful delivery of BTF from microemulsion-loaded hydrogel formulation, which resulted in improved penetration of drug and antifungal activity in comparison with commercial formulation of BTF.

Nasal delivery of chitosan-coated poly(lactide-co-glycolide)-encapsulated honeybee (Apis mellifera) venom promotes Th 1-specific systemic and local intestinal immune responses in weaned pigs.

PubMed

Lee, Jin-A; Kim, Yun-Mi; Kim, Tae-Hoon; Lee, Sang-Ho; Lee, Cho-A; Cho, Cheong-Weon; Jeon, Jong-Woon; Park, Jin-Kyu; Kim, Sang-Ki; Jung, Bock-Gie; Lee, Bong-Joo

2016-10-01

Nasal delivery is a convenient and acceptable route for drug administration, and has been shown to elicit a much more potent local and systemic response compared with other drug delivery routes. We previously demonstrated that rectal administration of poly(lactide-co-glycolide)-encapsulated honeybee venom (P-HBV) could enhance systemic Th 1-specific immune responses. We therefore synthesized chitosan-coated P-HBV (CP-HBV) and then evaluated the immune-boosting efficacy of nasally administered CP-HBV on systemic and local intestinal immunity compared with non-chitosan-coated P-HBV. The nasally delivered CP-HBV effectively enhanced Th 1-specific responses, eliciting a significant increase in the CD3(+)CD4(+)CD8(-) Th cell population, lymphocyte proliferation capacity, and expression of Th 1 cytokines (IFN-γ, IL-12, and IL-2) in peripheral blood mononuclear cells. Furthermore, these immune-boosting effects persisted up to 21days post CP-HBV administration. Nasal administration of CP-HBV also led to an increase of not only the CD4(+) Th 1 and IFN-γ secreting CD4(+) Th 1 cell population but also Th 1-specific cytokines and transcription factors, including IL-12, IFN-γ, STAT4, and T-bet, in isolated mononuclear cells from the spleen and ileum. Copyright © 2016 Elsevier B.V. All rights reserved.

Tips of the dual-lumen microcatheter-facilitated reverse wire technique in percutaneous coronary interventions for markedly angulated bifurcated lesions.

PubMed

Nomura, Tetsuya; Kikai, Masakazu; Hori, Yusuke; Yoshioka, Kenichi; Kubota, Hiroshi; Miyawaki, Daisuke; Urata, Ryota; Sugimoto, Takeshi; Keira, Natsuya; Tatsumi, Tetsuya

2018-04-01

In practical settings of percutaneous coronary intervention (PCI), we sometimes encounter difficulty in introducing a guidewire (GW) to the markedly angulated side branch (SB), and the reverse wire technique is considered as a last resort to overcome such a situation. We analyzed 12 cases that underwent PCI with dual-lumen microcatheter-facilitated reverse wire technique between January 2013 and July 2016. We retrospectively investigated the lesion's characteristics and the details of the PCI procedures, and discussed tips about the use of this technique. The SB that exhibits both a smaller take-off angle and a larger carina angle is considered to be the most suitable candidate for this technique. The first step of this technique involves the delivery of the reverse wire system to the target bifurcation. However, most cases exhibit significant stenosis proximal to the bifurcation, which often hampers the delivery of the reverse wire system. Because the sharply curved reverse wire system is easier to pass the stenosis as compared to the roundly curved system, we recommend a sharp curve should be adopted for this technique. On the other hand, it is sure that device delivery is much easier on the GW with a round curve as compared to that with a sharp curve. Therefore, it is important to modify the details of this procedure on a case-by-case basis according to the lesion's characteristics.

Comparing variation in hospital rates of cesarean delivery among low-risk women using 3 different measures.

PubMed

Armstrong, Joanne C; Kozhimannil, Katy B; McDermott, Patricia; Saade, George R; Srinivas, Sindhu K

2016-02-01

This report describes the development of a measure of low-risk cesarean delivery by the Society for Maternal-Fetal Medicine (SMFM). Safely lowering the cesarean delivery rate is a priority for maternity care clinicians and health care delivery systems. Therefore, hospital quality assurance programs are increasingly tracking cesarean delivery rates among low-risk pregnancies. Two commonly used definitions of "low risk" are available, the Joint Commission (JC) and the Agency for Healthcare Research and Quality (AHRQ) measures, but these measures are not clinically comprehensive. We sought to refine the definition of the low-risk cesarean delivery rate to enhance the validity of the metric for quality measurement. We created this refined definition-called the SMFM definition-and compared it to the JC and AHRQ measures using claims-based data from the 2011 Nationwide Inpatient Sample of >863,000 births in 612 hospitals. Using these definitions, we calculated means and interquartile ranges (25th-75th percentile range) for hospital low-risk cesarean delivery rates, stratified by hospital size, teaching status, urban/rural location, and payer mix. Across all hospitals, the mean low-risk cesarean delivery rate was lowest for the SMFM definition (12.65%), but not substantially different from the JC and AHRQ measures (13.12% and 13.29%, respectively). We empirically examined the SMFM definition to ensure its validity and utility. This refined definition performs similarly to existing measures and has the added advantage of clinical perspective, enhanced face validity, and ease of use. Copyright © 2016 Elsevier Inc. All rights reserved.

Patient injuries from anesthesia gas delivery equipment: a closed claims update.

PubMed

Mehta, Sonya P; Eisenkraft, James B; Posner, Karen L; Domino, Karen B

2013-10-01

Improvements in anesthesia gas delivery equipment and provider training may increase patient safety. The authors analyzed patient injuries related to gas delivery equipment claims from the American Society of Anesthesiologists Closed Claims Project database over the decades from 1970s to the 2000s. After the Institutional Review Board approval, the authors reviewed the Closed Claims Project database of 9,806 total claims. Inclusion criteria were general anesthesia for surgical or obstetric anesthesia care (n = 6,022). Anesthesia gas delivery equipment was defined as any device used to convey gas to or from (but not involving) the airway management device. Claims related to anesthesia gas delivery equipment were compared between time periods by chi-square test, Fisher exact test, and Mann-Whitney U test. Anesthesia gas delivery claims decreased over the decades (P < 0.001) to 1% of claims in the 2000s. Outcomes in claims from 1990 to 2011 (n = 40) were less severe, with a greater proportion of awareness (n = 9, 23%; P = 0.003) and pneumothorax (n = 7, 18%; P = 0.047). Severe injuries (death/permanent brain damage) occurred in supplemental oxygen supply events outside the operating room, breathing circuit events, or ventilator mishaps. The majority (85%) of claims involved provider error with (n = 7) or without (n = 27) equipment failure. Thirty-five percent of claims were judged as preventable by preanesthesia machine check. Gas delivery equipment claims in the Closed Claims Project database decreased in 1990-2011 compared with earlier decades. Provider error contributed to severe injury, especially with inadequate alarms, improvised oxygen delivery systems, and misdiagnosis or treatment of breathing circuit events.

Nanoparticles for cancer gene therapy: Recent advances, challenges, and strategies.

PubMed

Wang, Kui; Kievit, Forrest M; Zhang, Miqin

2016-12-01

Compared to conventional treatments, gene therapy offers a variety of advantages for cancer treatment including high potency and specificity, low off-target toxicity, and delivery of multiple genes that concurrently target cancer tumorigenesis, recurrence, and drug resistance. In the past decades, gene therapy has undergone remarkable progress, and is now poised to become a first line therapy for cancer. Among various gene delivery systems, nanoparticles have attracted much attention because of their desirable characteristics including low toxicity profiles, well-controlled and high gene delivery efficiency, and multi-functionalities. This review provides an overview on gene therapeutics and gene delivery technologies, and highlight recent advances, challenges and insights into the design and the utility of nanoparticles in gene therapy for cancer treatment. Copyright © 2016. Published by Elsevier Ltd.

Fast range measurement of spot scanning proton beams using a volumetric liquid scintillator detector.

PubMed

Hui, CheukKai; Robertson, Daniel; Alsanea, Fahed; Beddar, Sam

2015-08-01

Accurate confirmation and verification of the range of spot scanning proton beams is crucial for correct dose delivery. Current methods to measure proton beam range using ionization chambers are either time-consuming or result in measurements with poor spatial resolution. The large-volume liquid scintillator detector allows real-time measurements of the entire dose profile of a spot scanning proton beam. Thus, liquid scintillator detectors are an ideal tool for measuring the proton beam range for commissioning and quality assurance. However, optical artefacts may decrease the accuracy of measuring the proton beam range within the scintillator tank. The purpose of the current study was to 1) develop a geometric calibration system to accurately calculate physical distances within the liquid scintillator detector, taking into account optical artefacts; and 2) assess the accuracy, consistency, and robustness of proton beam range measurement using the liquid scintillator detector with our geometric calibration system. The range of the proton beam was measured with the calibrated liquid scintillator system and was compared to the nominal range. Measurements were made on three different days to evaluate the setup robustness from day to day, and three sets of measurements were made for each day to evaluate the consistency from delivery to delivery. All proton beam ranges measured using the liquid scintillator system were within half a millimeter of the nominal range. The delivery-to-delivery standard deviation of the range measurement was 0.04 mm, and the day-to-day standard deviation was 0.10 mm. In addition to the accuracy and robustness demonstrated by these results when our geometric calibration system was used, the liquid scintillator system allowed the range of all 94 proton beams to be measured in just two deliveries, making the liquid scintillator detector a perfect tool for range measurement of spot scanning proton beams.

Fast range measurement of spot scanning proton beams using a volumetric liquid scintillator detector

PubMed Central

Hui, CheukKai; Robertson, Daniel; Alsanea, Fahed; Beddar, Sam

2016-01-01

Accurate confirmation and verification of the range of spot scanning proton beams is crucial for correct dose delivery. Current methods to measure proton beam range using ionization chambers are either time-consuming or result in measurements with poor spatial resolution. The large-volume liquid scintillator detector allows real-time measurements of the entire dose profile of a spot scanning proton beam. Thus, liquid scintillator detectors are an ideal tool for measuring the proton beam range for commissioning and quality assurance. However, optical artefacts may decrease the accuracy of measuring the proton beam range within the scintillator tank. The purpose of the current study was to 1) develop a geometric calibration system to accurately calculate physical distances within the liquid scintillator detector, taking into account optical artefacts; and 2) assess the accuracy, consistency, and robustness of proton beam range measurement using the liquid scintillator detector with our geometric calibration system. The range of the proton beam was measured with the calibrated liquid scintillator system and was compared to the nominal range. Measurements were made on three different days to evaluate the setup robustness from day to day, and three sets of measurements were made for each day to evaluate the consistency from delivery to delivery. All proton beam ranges measured using the liquid scintillator system were within half a millimeter of the nominal range. The delivery-to-delivery standard deviation of the range measurement was 0.04 mm, and the day-to-day standard deviation was 0.10 mm. In addition to the accuracy and robustness demonstrated by these results when our geometric calibration system was used, the liquid scintillator system allowed the range of all 94 proton beams to be measured in just two deliveries, making the liquid scintillator detector a perfect tool for range measurement of spot scanning proton beams. PMID:27274863

Design of novel multifunctional targeting nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition.

PubMed

Chen, Daquan; Lian, Shengnan; Sun, Jingfang; Liu, Zongliang; Zhao, Feng; Jiang, Yongtao; Gao, Mingming; Sun, Kaoxiang; Liu, Wanhui; Fu, Fenghua

2016-01-01

In this study, to develop a multifunctional targeting nano-carrier drug delivery system for cancer therapy, the novel pH-sensitive ketal based oligosaccharides of hyaluronan (oHA) conjugates were synthesized by chemical conjugation of hydrophobic menthone 1,2-glycerol ketal (MGK) to the backbone of oHA with the histidine as the linker of proton sponge effect. The multifunctional oHA conjugates, oHA-histidine-MGK (oHM) carried the pH-sensitive MGK as hydrophobic moieties and oHA as the target of CD44 receptor. The oHM could self-assemble to nano-sized spherical shape with the average diameters of 128.6 nm at pH 7.4 PBS conditions. The oHM nanoparticles (oHMN) could release encapsulated curcumin (Cur) with 82.6% at pH 5.0 compared with 49.3% at pH 7.4. The results of cytotoxicity assay indicated that encapsulated Cur in oHMN (Cur-oHMN) were stable and have less toxicity compared to Cur suspension. The anti-tumor efficacy in vivo suggested that Cur-oHMN suppressed tumor growth most efficiently. These results present the promising potential of oHMN as a stable and effective nano-sized pH-sensitive drug delivery system for cancer treatment.

Studies on self-nanoemulsifying drug delivery system of flurbiprofen employing long, medium and short chain triglycerides.

PubMed

Daar, Junaid; Khan, Ahmad; Khan, Jallat; Khan, Amjad; Khan, Gul Majid

2017-03-01

The aim of the study was to successfully design, formulate and evaluate self-nanoemulsifying drug delivery system (SNEDDS) of poorly aqueous soluble drug viz. flurbiprofen using long (LCT), medium (MCT) and short chain triglycerides (SCT). The SNEDDS are thermodynamically stable lipid based drug delivery systems which consist of mixture of oil, surfactant and co-surfactant. Upon aqueous dilution, this mixture produces nano-emulsion spontaneously on slight agitation. The excipients intended to be used were screened for their potential to dissolve the drug and to form clear dispersion upon aqueous dilution. Labrafil M 1944 CS, capryol-90 and triacetin were selected as long, medium and short chain triglycerides, respectively, as lipids while tween-80 and polyethylene glycol-400 (PEG-400)/ethanol (3:1 ratio) were selected as surfactant and co-surfactant, respectively. The excipients were studied at every possible combination ratios using pseudo-ternary diagram. The LCT, MCT and SCT-SNEDDS were optimized using thermodynamic studies, percentage transmittance value, viscosity, refractive index (RI), electrical conductivity, globule size analysis and in-vitro drug release studies. The drug release profiles of optimized SNEDDS were then compared with market product at different pH mediums. The LCT-SNEDDS was considered to be superior for enhancement of the drug bioavailability when compared with other SNEDDS formulations and market product.

Combined effects of the drug distribution and mucus diffusion properties of self-microemulsifying drug delivery systems on the oral absorption of fenofibrate.

PubMed

Sunazuka, Yushi; Ueda, Keisuke; Higashi, Kenjirou; Tanaka, Yusuke; Moribe, Kunikazu

2018-05-24

We present the absorption improvement mechanism of fenofibrate (FFB), a Biopharmaceutics Classification System (BCS) class II drug, from self-microemulsifying drug delivery systems (SMEDDS), centered on improving the diffusion of FFB through the unstirred water layer (UWL). Four SMEDDS formulations containing Labrafac™ lipophile WL 1349 (WL1349) or Labrafil ® M 1944CS (M1944) oils and NIKKOL HCO-40 (HCO40) or NIKKOL HCO-60 (HCO60) surfactants were prepared. Every SMEDDS formulation formed microemulsion droplets of approximately 30 nm. In vitro tests showed that the microemulsion droplets containing M1944 had relatively small FFB solubilization capacities, causing larger amounts of FFB to be dissolved in the bulk water phase, compared to the droplets containing WL1349. The diffusivity of the microemulsion droplets through the mucin solution layer was enhanced when using HCO40 compared to HCO60. The oral absorption in rats was the highest when using the SMEDDS formulation containing M1944 and HCO40. High FFB distribution in the bulk water phase and fast diffusion of microemulsion droplets through the mucus layer contributed to the efficient delivery of FFB molecules through the UWL to the epithelial cells, leading to enhanced FFB absorption. Copyright © 2018 Elsevier B.V. All rights reserved.

Chitosan-based thermosensitive hydrogel as a promising ocular drug delivery system: preparation, characterization, and in vivo evaluation.

PubMed

Chen, Xingwei; Li, Xinru; Zhou, Yanxia; Wang, Xiaoning; Zhang, Yanhui; Fan, Yating; Huang, Yanqing; Liu, Yan

2012-11-01

The purpose of this study was to evaluate the feasibility of in situ thermosensitive hydrogel based on chitosan in combination with disodium α-d-Glucose 1-phosphate (DGP) for ocular drug delivery system. Aqueous solution of chitosan/DGP underwent sol-gel transition as temperature increased which was flowing sol at room temperature and then turned into non-flowing hydrogel at physiological temperature. The properties of gels were characterized regarding gelation time, gelation temperature, and morphology. The sol-to-gel phase transition behaviors were affected by the concentrations of chitosan, DGP and the model drug levocetirizine dihydrochloride (LD). The developed hydrogel presented a characteristic of a rapid release at the initial period followed by a sustained release and remarkably enhanced the cornea penetration of LD. The results of ocular irritation demonstrated the excellent ocular tolerance of the hydrogel. The ocular residence time for the hydrogel was significantly prolonged compared with eye drops. The drug-loaded hydrogel produced more effective anti-allergic conjunctivitis effects compared with LD aqueous solution. These results showed that the chitosan/DGP thermosensitive hydrogel could be used as an ideal ocular drug delivery system in terms of the suitable sol-gel transition temperature, mild pH environment in the hydrogel as well as the organic solvent free.

Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

PubMed Central

Zhang, Youwen; Tong, Deyin; Che, Daobiao; Pei, Bing; Xia, Xiaodong; Yuan, Gaofeng; Jin, Xin

2017-01-01

The roles of ginsenoside compound K (CK) in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP)/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS) mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 μg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects. PMID:28144142

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.

Preparation and evaluation of injectable Rasagiline mesylate dual-controlled drug delivery system for the treatment of Parkinson's disease.

PubMed

Jiang, Ying; Zhang, Xuemei; Mu, Hongjie; Hua, Hongchen; Duan, Dongyu; Yan, Xiuju; Wang, Yiyun; Meng, Qingqing; Lu, Xiaoyan; Wang, Aiping; Liu, Wanhui; Li, Youxin; Sun, Kaoxiang

2018-11-01

A microsphere-gel in situ forming implant (MS-Gel ISFI) dual-controlled drug delivery system was applied to a high water-soluble small-molecule compound Rasagiline mesylate (RM) for effective treatment of Parkinson's disease. This injectable complex depot system combined an in situ phase transition gel with high drug-loading and encapsulation efficiency RM-MS prepared by a modified emulsion-phase separation method and optimized by Box-Behnken design. It was evaluated for in vitro drug release, in vivo pharmacokinetics, and in vivo pharmacodynamics. We found that the RM-MS-Gel ISFI system showed no initial burst release and had a long period of in vitro drug release (60 days). An in vivo pharmacokinetic study indicated a significant reduction (p < .01) in the initial high plasma drug concentration of the RM-MS-Gel ISFI system compared to that of the single RM-MS and RM-in situ gel systems after intramuscular injection to rats. A pharmacodynamic study demonstrated a significant reduction (p < .05) in 6-hydroxydopamine-induced contralateral rotation behavior and an effective improvement (p < .05) in dopamine levels in the striatum of the lesioned side after 28 days in animals treated with the RM-MS-Gel ISFI compared with that of animals treated with saline. MS-embedded in situ phase transition gel is superior for use as a biodegradable and injectable sustained drug delivery system with a low initial burst and long period of drug release for highly hydrophilic small molecule drugs.

Developing Effective Linkages between Job Corps and One-Stop Systems: A Technical Assistance Guide.

ERIC Educational Resources Information Center

Dickinson, Katherine; Soukamneuth, Sengsouvanh

This document is intended to help Job Corps centers and Office of Acquisition Policy contractors establish linkages with one-stop systems. Chapter 1 summarizes the requirements for linkages between Job Corps and one-stop systems that are specified in the Workforce Investment Act (WIA) of 1998 and compares one-stop delivery systems before and under…

Novel nanocarriers for topical drug delivery: investigating delivery efficiency and distribution in skin using two-photon microscopy

NASA Astrophysics Data System (ADS)

Kirejev, Vladimir; Guldbrand, Stina; Bauer, Brigitte; Smedh, Maria; Ericson, Marica B.

2011-03-01

The complex structure of skin represents an effective barrier against external environmental factors, as for example, different chemical and biochemical compounds, yeast, bacterial and viral infections. However, this impermeability prevents efficient transdermal drug delivery which limits the number of drugs that are able to penetrate the skin efficiently. Current trends in drug application through skin focus on the design and use of nanocarriers for transport of active compounds. The transport systems applied so far have several drawbacks, as they often have low payload, high toxicity, a limited variability of inclusion molecules, or long degradation times. The aim of these current studies is to investigate novel topical drug delivery systems, e.g. nanocarriers based on cyclic oligosaccharides - cyclodextrins (CD) or iron (III)-based metal-organic frameworks (MOF). Earlier studies on cell cultures imply that these drug nanocarriers show promising characteristics compared to other drug delivery systems. In our studies, we use two-photon microscopy to investigate the ability of the nanocarriers to deliver compounds through ex-vivo skin samples. Using near infrared light for excitation in the so called optical window of skin allows deep-tissue visualization of drug distribution and localization. In addition, it is possible to employ two-photon based fluorescence correlation spectroscopy for quantitative analysis of drug distribution and concentrations in different cell layers.

In Vitro and In Vivo Evaluation of a Hydrogel Reservoir as a Continuous Drug Delivery System for Inner Ear Treatment

PubMed Central

Hessler, Roland; Stöver, Timo; Esser, Karl-Heinz; Möller, Martin; Lenarz, Thomas; Jolly, Claude; Groll, Jürgen; Scheper, Verena

2014-01-01

Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear. PMID:25105670

Methods for Engaging Stakeholders in Comparative Effectiveness Research: A Patient-Centered Approach to Improving Diabetes Care

PubMed Central

Schmittdiel, Julie A.; Desai, Jay; Schroeder, Emily B.; Paolino, Andrea R.; Nichols, Gregory A.; Lawrence, Jean M.; O’Connor, Patrick J.; Ohnsorg, Kris A.; Newton, Katherine M.; Steiner, John F.

2016-01-01

ABSTRACT/Implementation Lessons Engaging stakeholders in the research process has the potential to improve quality of care and the patient care experience.Online patient community surveys can elicit important topic areas for comparative effectiveness research.Stakeholder meetings with substantial patient representation, as well as representation from health care delivery systems and research funding agencies, are a valuable tool for selecting and refining pilot research and quality improvement projects.Giving patient stakeholders a deciding vote in selecting pilot research topics helps ensure their ‘voice’ is heard.Researchers and health care leaders should continue to develop best-practices and strategies for increasing patient involvement in comparative effectiveness and delivery science research. PMID:26179728

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

PubMed

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

2017-11-01

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

Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration.

PubMed

Wood, Matthew D; MacEwan, Matthew R; French, Alexander R; Moore, Amy M; Hunter, Daniel A; Mackinnon, Susan E; Moran, Daniel W; Borschel, Gregory H; Sakiyama-Elbert, Shelly E

2010-08-15

Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury.

A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media.

PubMed

Kotla, Niranjan G; Singh, Sima; Maddiboyina, Balaji; Sunnapu, Omprakash; Webster, Thomas J

2016-01-01

The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and 5% w/v grade "A" honey. Approximately 10(10)-10(11) colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials' community by elucidating an easier assay for colonic drug delivery.

Enhanced colonic delivery of ciclosporin A self-emulsifying drug delivery system encapsulated in coated minispheres.

PubMed

Keohane, Kieran; Rosa, Mónica; Coulter, Ivan S; Griffin, Brendan T

2016-01-01

Investigate the potential of coated minispheres (SmPill®) to enhance localized Ciclosporin A (CsA) delivery to the colon. CsA self-emulsifying drug delivery systems (SEDDS) were encapsulated into SmPill® minispheres. Varying degrees of coating thickness (low, medium and high) were applied using ethylcellulose and pectin (E:P) polymers. In vitro CsA release was evaluated in simulated gastric and intestinal media. Bioavailability of CsA in vivo following oral administration to pigs of SmPill® minispheres was compared to Neoral® po and Sandimmun® iv in a pig model. CsA concentrations in blood and intestinal tissue were determined by HPLC-UV. In vitro CsA release from coated minispheres decreased with increasing coating thickness. A linear relationship was observed between in vitro CsA release and in vivo bioavailability (r(2) = 0.98). CsA concentrations in the proximal, transverse and distal colon were significantly higher following administration of SmPill®, compared to Neoral® po and Sandimmun® iv (p < 0.05). Analysis of transverse colon tissue subsections also revealed significantly higher CsA concentrations in the mucosa and submucosa using SmPill® minispheres (p < 0.05). Modulating E:P coating thickness controls release of CsA from SmPill® minispheres. Coated minispheres limited CsA release in the small intestine and enhanced delivery and uptake in the colon. These findings demonstrate clinical advantages of an oral coated minisphere-enabled CsA formulation in the treatment of inflammatory conditions of the large intestine.

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

PubMed

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

2014-01-01

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

Gx1-conjugated endostar nanoparticle: a new drug delivery system for anti-colorectal cancer in vivo

NASA Astrophysics Data System (ADS)

Zhang, Qian; Du, Yang; Li, Yaqian; Liang, Xiaolong; Yang, Xin; Tian, Jie

2014-03-01

In this study we describe a new theranostic nanostytem to combine those functions together. GX1, the peptide identified by phage display technology, is a tumor vasculature endothelium specific ligand. Endostar, a novel recombinant human endostatin, has been proved to inhibit tumor angiogenesis. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and then GX1 was coupled to the surface of EPNPs for targeting therapy, last a near infrared (NIR) dye IRDye 800CW was conjugated to the surface of EPNPs for monitoring the biodistributon. This GX1-EPNPs-NIR dye IRDye 800CW (GEN) multifunction drug delivery system not only facilitates efficient delivery of chemotherapeutic agents to tumor site, while minimizing systemic toxicity and side effects, but also enables to real time monitor tumor targeting in vivo. Compare to the Endostar and EPNPs, the GEN inhibited the subcutaneous colon tumor more obviously both in tumor volume and bioluminescence imaging (BLI) light intensity during the 10 days drug treatment.

Novel vaginal drug delivery system: deformable propylene glycol liposomes-in-hydrogel.

PubMed

Vanić, Željka; Hurler, Julia; Ferderber, Kristina; Golja Gašparović, Petra; Škalko-Basnet, Nataša; Filipović-Grčić, Jelena

2014-03-01

Deformable propylene glycol-containing liposomes (DPGLs) incorporating metronidazole or clotrimazole were prepared and evaluated as an efficient drug delivery system to improve the treatment of vaginal microbial infections. The liposome formulations were optimized based on sufficient trapping efficiencies for both drugs and membrane elasticity as a prerequisite for successful permeability and therapy. An appropriate viscosity for vaginal administration was achieved by incorporating the liposomes into Carbopol hydrogel. DPGLs were able to penetrate through the hydrogel network more rapidly than conventional liposomes. In vitro studies of drug release from the liposomal hydrogel under conditions simulating human treatment confirmed sustained and diffusion-based drug release. Characterization of the rheological and textural properties of the DPGL-containing liposomal hydrogels demonstrated that the incorporation of DPGLs alone had no significant influence on mechanical properties of hydrogels compared to controls. These results support the great potential of DPGL-in-hydrogel as an efficient delivery system for the controlled and sustained release of antimicrobial drugs in the vagina.

Development of amino acid substituted gemini surfactant-based mucoadhesive gene delivery systems for potential use as noninvasive vaginal genetic vaccination.

PubMed

Singh, Jagbir; Michel, Deborah; Getson, Heather M; Chitanda, Jackson M; Verrall, Ronald E; Badea, Ildiko

2015-02-01

Recently, we synthesized amino acid- and peptide-substituted gemini surfactants, 'biolipids' that exhibited high transfection efficiency in vitro. In this study, we developed these plasmid DNA and gemini surfactant lipid particles for noninvasive administration in vaginal cavity. Novel formulations of these gene delivery systems were prepared with poloxamer 407 to induce in situ gelling of the formulation and diethylene glycol monoethyl ether to improve their penetration across mucosal tissue. Poloxamer at 16% w/v concentration in diethylene glycol monoethyl ether aqueous solution produced dispersions that gelled near body temperature and had a high yield value, preventing leakage of the formulation from the vaginal cavity. Intravaginal administration in rabbits showed that the glycyl-lysine-substituted gemini surfactant led to a higher gene expression compared with the parent unsubstituted gemini surfactant. This provides a proof-of-concept that amino acid substituted gemini surfactants can be used as noninvasive mucosal (vaginal) gene delivery systems to treat diseases associated with mucosal epithelia.

Combined effects of prenatal medication use and delivery type are associated with eczema at age 2 years.

PubMed

Wegienka, G; Havstad, S; Zoratti, E M; Kim, H; Ownby, D R; Johnson, C C

2015-03-01

Separately, prenatal antibiotics and Caesarian delivery have been found to be associated with increased risk of allergic diseases. It is not clear whether these factors may modify the effect of each other. To assess whether the associations between delivery types and eczema, sensitization and total IgE at age 2 years were modified by maternal use of prenatal medications. Prenatal charts of women enrolled in the WHEALS birth cohort were reviewed for delivery mode and medications prescribed and administered throughout their entire pregnancy, including systemic antibiotics and vaginally applied antifungal medications. The associations between the delivery mode and select medications and, eczema, sensitization (≥ 1 of 10 allergen-specific IgE ≥ 0.35 IU/mL) and total IgE at age 2 years were assessed. There was a lower risk of eczema among vaginally vs. c-section born children (relative risk adjusted for race = aRR = 0.77, 95% CI 0.56, 1.05). Although not statistically significantly different, this association was stronger among the subset of children born vaginally to a mother who did not use systemic antibiotics or vaginal antifungal medications (aRR = 0.69, 95% CI 0.44, 1.08) compared to those born vaginally to mothers who used systemic antibiotics or vaginal antifungals (aRR = 0.81, 95% CI 0.57, 1.14). A protective association between vaginal birth and sensitization (aRR = 0.86, 95% CI 0.72, 1.03) was similar for those children born vaginally to a mother who did not (aRR = 0.87, 95% CI 0.69, 1.10) and who did (RR = 0.85, 95% CI 0.70, 1.04) use systemic antibiotics or vaginal antifungal medications. There were no associations with total IgE. Children born vaginally had lower risk of eczema and sensitization compared with those born via c-section; however, the protective association with eczema may be slightly weakened when mothers took systemic antibiotics or vaginally applied medications during pregnancy. © 2014 John Wiley & Sons Ltd.

Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases

NASA Astrophysics Data System (ADS)

Fornaguera, C.; Feiner-Gracia, N.; Calderó, G.; García-Celma, M. J.; Solans, C.

2015-07-01

Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases.Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03474d

PDGF-B Gene Therapy Accelerates Bone Engineering and Oral Implant Osseointegration

PubMed Central

Chang, Po-Chun; Seol, Yang-Jo; Cirelli, Joni A; Pellegrini, Gaia R.; Jin, Qiming; Franco, Lea M.; Goldstein, Steven A.; Chandler, Lois A.; Sosnowski, Barbara; Giannobile, William V.

2009-01-01

Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due in part to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5×108 or 5.5×109 pfu/ml), Ad encoding luciferase (Ad-Luc; 5.5×109 pfu/ml; control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg/ml). Bone repair and osseointegration were measured via backscattered SEM, histomorphometry, microcomputed tomography, and biomechanical assessments. Further, a panel of local and systemic safety assessments was performed. Results demonstrated bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared to Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B demonstrates regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable to rhPDGF-BB protein delivery in vivo. PMID:19741730

Single-step assembly of polymer-lipid hybrid nanoparticles for mitomycin C delivery

PubMed Central

2014-01-01

Mitomycin C is one of the most effective chemotherapeutic agents for a wide spectrum of cancers, but its clinical use is still hindered by the mitomycin C (MMC) delivery systems. In this study, the MMC-loaded polymer-lipid hybrid nanoparticles (NPs) were prepared by a single-step assembly (ACS Nano 2012, 6:4955 to 4965) of MMC-soybean phosphatidyhlcholine (SPC) complex (Mol. Pharmaceutics 2013, 10:90 to 101) and biodegradable polylactic acid (PLA) polymers for intravenous MMC delivery. The advantage of the MMC-SPC complex on the polymer-lipid hybrid NPs was that MMC-SPC was used as a structural element to offer the integrity of the hybrid NPs, served as a drug preparation to increase the effectiveness and safety and control the release of MMC, and acted as an emulsifier to facilitate and stabilize the formation. Compared to the PLA NPs/MMC, the PLA NPs/MMC-SPC showed a significant accumulation of MMC in the nuclei as the action site of MMC. The PLA NPs/MMC-SPC also exhibited a significantly higher anticancer effect compared to the PLA NPs/MMC or free MMC injection in vitro and in vivo. These results suggested that the MMC-loaded polymer-lipid hybrid NPs might be useful and efficient drug delivery systems for widening the therapeutic window of MMC and bringing the clinical use of MMC one step closer to reality. PMID:25324707

Quadruplet pregnancy: contemporary management and outcome.

PubMed

Elliott, J P; Radin, T G

1992-09-01

Quadruplets are occurring more frequently as assisted-reproduction techniques improve fertility in couples previously unable to conceive. Ten quadruplet pregnancies cared for in one perinatal practice over 5 years had excellent outcome. The mean gestational age at delivery was 32.5 weeks, compared with approximately 30 weeks in the literature. There were no perinatal deaths and no long-term morbidity. Our patients were compared with a series of 57 consecutive patients with quadruplet pregnancies monitored by a home monitoring system. Parity of 1 or more appeared to improve outcome. Pregnancy-induced hypertension occurred in nine of our pregnancies and necessitated delivery in seven instances. Fetal distress was responsible for two deliveries and uncontrollable preterm labor for only one. Key points in our management protocol include prophylactic use of low-dose aspirin, home contraction monitoring, use of terbutaline pump tocolysis, and bed rest at home starting at 16 weeks.

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

PubMed Central

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

2012-01-01

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

Laser-induced changes in intraretinal oxygen distribution in pigmented rabbits.

PubMed

Yu, Dao-Yi; Cringle, Stephen J; Su, Erning; Yu, Paula K; Humayun, Mark S; Dorin, Giorgio

2005-03-01

To make the first measurements of intraretinal oxygen distribution and consumption after laser photocoagulation of the retina and to compare the efficiency of micropulsed (MP) and continuous wave (CW) laser delivery in achieving an oxygen benefit in the treated area. Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of retinal depth before and after laser treatment in anesthetized, mechanically ventilated, Dutch Belted rabbits (n = 11). Laser lesions were created by using a range of power levels from an 810-nm diode laser coupled with an operating microscope delivery system. MP duty cycles of 5%, 10%, and 15% were compared with CW delivery in each eye. Sufficient power levels of both the CW and MP laser reduced outer retinal oxygen consumption and increased oxygen level within the retina. At these power levels, which correlated with funduscopically visible lesions, there was histologically visible damage to the RPE and photoreceptors. Retinal damage was energy dependent but short-duty-cycle MP delivery was more selective in terms of retinal cell damage, with a wider safety range in comparison with CW delivery. The relationship between laser power level and mode of delivery and the resultant changes in oxygen metabolism and oxygen level in the retina was determined. Only partial destruction of RPE and photoreceptors is necessary, to produce a measurable oxygen benefit in the treated area of retina.

Endurance Exercise: Normal Physiology and Limitations Imposed by Pathological Processes (Part 1).

ERIC Educational Resources Information Center

Frontera, Walter R.; Adams, Richard P.

1986-01-01

The physiologic and metabolic adjustments of the body to a single endurance exercise session are analyzed in terms of the respiratory system, the cardiovascular system, and oxygen delivery to the muscles. Patients with cardiorespiratory and neuromuscular diseases are compared to normal individuals. (Author/MT)

Fleximode: Within Western Australia TAFE.

ERIC Educational Resources Information Center

Toussaint, Dorothy

After fleximode was introduced into the Western Australian TAFE system, its cost and effectiveness compared with traditional delivery systems were evaluated. Fleximode, as practiced in Australia, was adapted from a mode of study pioneered in England. It offered students the independence of off-campus study in combination with access to college…

Stop Contributing to Our People's Genocide. The Role of Community Prevention.

ERIC Educational Resources Information Center

New Breast, Theda

1990-01-01

Outlines a community action process that American Indian communities could use to develop their own drug and alcohol abuse prevention programs. Describes a community prevention system framework developed by the Office of Substance Abuse Prevention. Compares the community empowerment system with the agency-directed service delivery model. (SV)

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

Nguyen, Kham, E-mail: khamdiep@gmail.com; UT MD Anderson Cancer Center, School of Health Professions—Unit 2, Houston, TX; Cummings, David

The purpose of this study was to evaluate the differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in the treatment of nasal cavity carcinomas. The treatment of 10 patients, who had completed IMRT treatment for resected tumors of the nasal cavity, was replanned with the Philips Pinnacle{sup 3} Version 9 treatment-planning system. The IMRT plans used a 9-beam technique whereas the VMAT (known as SmartArc) plans used a 3-arc technique. Both types of plans were optimized using Philips Pinnacle{sup 3} Direct Machine Parameter Optimization algorithm. IMRT and VMAT plans' quality was compared by evaluating the maximum,more » minimum, and mean doses to the target volumes and organs at risk, monitor units (MUs), and the treatment delivery time. Our results indicate that VMAT is capable of greatly reducing treatment delivery time and MUs compared with IMRT. The reduction of treatment delivery time and MUs can decrease the effects of intrafractional uncertainties that can occur because of patient movement during treatment delivery. VMAT's plans further reduce doses to critical structures that are in close proximity to the target volume.« less

Nanoparticles Suitable for BCAA Isolation Can Serve for Use in Magnetic Lipoplex-Based Delivery System for L, I, V, or R-rich Antimicrobial Peptides.

PubMed

Vesely, Radek; Jelinkova, Pavlina; Hegerova, Dagmar; Cernei, Natalia; Kopel, Pavel; Moulick, Amitava; Richtera, Lukas; Heger, Zbynek; Adam, Vojtech; Zitka, Ondrej

2016-03-31

This paper investigates the synthesis of paramagnetic nanoparticles, which are able to bind branched chain amino acids (BCAAs)-leucine, valine, and isoleucine and, thus, serve as a tool for their isolation. Further, by this, we present an approach for encapsulation of nanoparticles into a liposome cavity resulting in a delivery system. Analyses of valine and leucine in entire complex show that 31.3% and 32.6% recoveries are reached for those amino acids. Evaluation of results shows that the success rate of delivery in Escherichia coli ( E. coli ) is higher in the case of BCAAs on nanoparticles entrapped in liposomes (28.7% and 34.7% for valine and leucine, respectively) when compared to nanoparticles with no liposomal envelope (18.3% and 13.7% for valine and leucine, respectively). The nanoparticles with no liposomal envelope exhibit the negative zeta potential (-9.1 ± 0.3 mV); however, their encapsulation results in a shift into positive values (range of 28.9 ± 0.4 to 33.1 ± 0.5 mV). Thus, electrostatic interactions with negatively-charged cell membranes (approx. -50 mV in the case of E. coli ) leads to a better uptake of cargo. Our delivery system was finally tested with the leucine-rich antimicrobial peptide (FALALKALKKALKKLKKALKKAL) and it is shown that hemocompatibility (7.5%) and antimicrobial activity of the entire complex against E. coli , Staphylococcus aureus ( S. aureus ), and methicilin-resistant S. aureus (MRSA) is comparable or better than conventional penicillin antibiotics.

Soil chemical sensor and precision agricultural chemical delivery system and method

DOEpatents

Colburn, Jr., John W.

1991-01-01

A real time soil chemical sensor and precision agricultural chemical delivery system includes a plurality of ground-engaging tools in association with individual soil sensors which measure soil chemical levels. The system includes the addition of a solvent which rapidly saturates the soil/tool interface to form a conductive solution of chemicals leached from the soil. A multivalent electrode, positioned within a multivalent frame of the ground-engaging tool, applies a voltage or impresses a current between the electrode and the tool frame. A real-time soil chemical sensor and controller senses the electrochemical reaction resulting from the application of the voltage or current to the leachate, measures it by resistivity methods, and compares it against pre-set resistivity levels for substances leached by the solvent. Still greater precision is obtained by calibrating for the secondary current impressed through solvent-less soil. The appropriate concentration is then found and the servo-controlled delivery system applies the appropriate amount of fertilizer or agricultural chemicals substantially in the location from which the soil measurement was taken.

Oncolytic Adenovirus Complexes Coated with Lipids and Calcium Phosphate for Cancer Gene Therapy.

PubMed

Chen, Jianhua; Gao, Pei; Yuan, Sujing; Li, Rongxin; Ni, Aimin; Chu, Liang; Ding, Li; Sun, Ying; Liu, Xin-Yuan; Duan, Yourong

2016-12-27

Oncolytic adenovirus (Onco Ad ) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of Onco Ad is hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-Onco Ad (PLC-Onco Ad ) delivery system for ZD55-IL-24, an oncolytic adenovirus that carries the IL-24 gene. The negatively charged PLC-ZD55-IL-24 were disperse and resisted serum-induced aggregation. Compared to naked ZD55-IL-24, the systemic administration of PLC-ZD55-IL-24 in BALB/c mice resulted in reduced liver sequestration and systemic toxicity and evaded the innate immune response. In addition, masking the surface of Onco Ad protected it from neutralization by pre-existing neutralizing antibody. PLC-Onco Ad achieved efficient targeted delivery in Huh-7-bearing nude mice, and intravenous administration of a high dose of PLC-ZD55-IL-24 increased therapeutic efficacy without inducing toxicity. The developed PLC-Onco Ad delivery system represents a promising improvement for oncolytic adenovirus-based cancer gene therapy in vivo.

Nutraceutical delivery systems: resveratrol encapsulation in grape seed oil nanoemulsions formed by spontaneous emulsification.

PubMed

Davidov-Pardo, Gabriel; McClements, David Julian

2015-01-15

The aim of this work was to fabricate nanoemulsions-based delivery systems to encapsulate resveratrol. Nanoemulsions were formed using spontaneous emulsification method: 10% oil phase (grape seed oil plus orange oil) and 10% surfactant (Tween 80) were titrated into 80% aqueous phase. An optimum orange oil-to-grape seed oil ratio of 1:1(w/w) formed small droplets (d ≈ 100 nm) with good stability to droplet growth. The maximum amount of resveratrol that could be dissolved in the oil phase was 120 ± 10 μg/ml. The effect of droplet size on the chemical stability of encapsulated resveratrol was examined by preparing systems with different mean droplet diameters of 220 ± 2; 99 ± 3; and 45 ± 0.4 nm. Encapsulation of resveratrol improved its chemical stability after exposure to UV-light: 88% retention in nanoemulsions compared to 50% in dimethylsulphoxide (DMSO). This study showed that resveratrol could be encapsulated within low-energy nanoemulsion-based delivery systems and protected against degradation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Soil chemical sensor and precision agricultural chemical delivery system and method

DOEpatents

Colburn, J.W. Jr.

1991-07-23

A real time soil chemical sensor and precision agricultural chemical delivery system includes a plurality of ground-engaging tools in association with individual soil sensors which measure soil chemical levels. The system includes the addition of a solvent which rapidly saturates the soil/tool interface to form a conductive solution of chemicals leached from the soil. A multivalent electrode, positioned within a multivalent frame of the ground-engaging tool, applies a voltage or impresses a current between the electrode and the tool frame. A real-time soil chemical sensor and controller senses the electrochemical reaction resulting from the application of the voltage or current to the leachate, measures it by resistivity methods, and compares it against pre-set resistivity levels for substances leached by the solvent. Still greater precision is obtained by calibrating for the secondary current impressed through solvent-less soil. The appropriate concentration is then found and the servo-controlled delivery system applies the appropriate amount of fertilizer or agricultural chemicals substantially in the location from which the soil measurement was taken. 5 figures.

Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers-in vitro and in vivo studies.

PubMed

Madhumathi, K; Rubaiya, Y; Doble, Mukesh; Venkateswari, R; Sampath Kumar, T S

2018-05-01

A dual local drug delivery system (DDS) composed of calcium phosphate bioceramic nanocarriers aimed at treating the antibacterial, anti-inflammatory, and bone-regenerative aspects of periodontitis has been developed. Calcium-deficient hydroxyapatite (CDHA, Ca/P = 1.61) and tricalcium phosphate (β-TCP) were prepared by microwave-accelerated wet chemical synthesis method. The phase purity of the nanocarriers was confirmed by x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), while the transmission electron microscopy (TEM) confirmed their nanosized morphology. CDHA was selected as carrier for the antibiotic (tetracycline) while TCP was chosen as the anti-inflammatory drug (ibuprofen) carrier. Combined drug release profile was studied in vitro from CDHA/TCP (CTP) system and compared with a HA/TCP (BCP) biphasic system. The tetracycline and ibuprofen release rate was 71 and 23% from CTP system as compared to 63 and 20% from BCP system. CTP system also showed a more controlled drug release profile compared to BCP system. Modeling of drug release kinetics from CTP system indicated that the release follows Higuchi model with a non-typical Fickian diffusion profile. In vitro biological studies showed the CTP system to be biocompatible with significant antibacterial and anti-inflammatory activity. In vivo implantation studies on rat cranial defects showed greater bone healing and new bone formation in the drug-loaded CTP system compared to control (no carrier) at the end of 12 weeks. The in vitro and in vivo results suggest that the combined drug delivery platform can provide a comprehensive management for all bone infections requiring multi-drug therapy.

Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

PubMed

Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

2013-12-28

Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

Commissioning and quality assurance for VMAT delivery systems: An efficient time-resolved system using real-time EPID imaging.

PubMed

Zwan, Benjamin J; Barnes, Michael P; Hindmarsh, Jonathan; Lim, Seng B; Lovelock, Dale M; Fuangrod, Todsaporn; O'Connor, Daryl J; Keall, Paul J; Greer, Peter B

2017-08-01

An ideal commissioning and quality assurance (QA) program for Volumetric Modulated Arc Therapy (VMAT) delivery systems should assess the performance of each individual dynamic component as a function of gantry angle. Procedures within such a program should also be time-efficient, independent of the delivery system and be sensitive to all types of errors. The purpose of this work is to develop a system for automated time-resolved commissioning and QA of VMAT control systems which meets these criteria. The procedures developed within this work rely solely on images obtained, using an electronic portal imaging device (EPID) without the presence of a phantom. During the delivery of specially designed VMAT test plans, EPID frames were acquired at 9.5 Hz, using a frame grabber. The set of test plans was developed to individually assess the performance of the dose delivery and multileaf collimator (MLC) control systems under varying levels of delivery complexities. An in-house software tool was developed to automatically extract features from the EPID images and evaluate the following characteristics as a function of gantry angle: dose delivery accuracy, dose rate constancy, beam profile constancy, gantry speed constancy, dynamic MLC positioning accuracy, MLC speed and acceleration constancy, and synchronization between gantry angle, MLC positioning and dose rate. Machine log files were also acquired during each delivery and subsequently compared to information extracted from EPID image frames. The largest difference between measured and planned dose at any gantry angle was 0.8% which correlated with rapid changes in dose rate and gantry speed. For all other test plans, the dose delivered was within 0.25% of the planned dose for all gantry angles. Profile constancy was not found to vary with gantry angle for tests where gantry speed and dose rate were constant, however, for tests with varying dose rate and gantry speed, segments with lower dose rate and higher gantry speed exhibited less profile stability. MLC positional accuracy was not observed to be dependent on the degree of interdigitation. MLC speed was measured for each individual leaf and slower leaf speeds were shown to be compensated for by lower dose rates. The test procedures were found to be sensitive to 1 mm systematic MLC errors, 1 mm random MLC errors, 0.4 mm MLC gap errors and synchronization errors between the MLC, dose rate and gantry angle controls systems of 1°. In general, parameters measured by both EPID and log files agreed with the plan, however, a greater average departure from the plan was evidenced by the EPID measurements. QA test plans and analysis methods have been developed to assess the performance of each dynamic component of VMAT deliveries individually and as a function of gantry angle. This methodology relies solely on time-resolved EPID imaging without the presence of a phantom and has been shown to be sensitive to a range of delivery errors. The procedures developed in this work are both comprehensive and time-efficient and can be used for streamlined commissioning and QA of VMAT delivery systems. © 2017 American Association of Physicists in Medicine.

Computerized Coordinated Service Center: A Comparison of Service Methodologies and Costs in the Urban and Rural Area.

ERIC Educational Resources Information Center

Waldman, Risa J.; And Others

Ten parallel human service agencies (five urban and five rural) were compared to identify variations in the service delivery system and to compare the costs of service provision. The agencies responded to approximately 36 questions covering eight major areas and were compared and contrasted, urban versus rural, according to the type of agency. All…

Stimuli-free programmable drug release for combination chemo-therapy

NASA Astrophysics Data System (ADS)

Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

2016-06-01

Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06305a

A Safe Bacterial Microsyringe for In Vivo Antigen Delivery and Immunotherapy

PubMed Central

Le Gouëllec, Audrey; Chauchet, Xavier; Laurin, David; Aspord, Caroline; Verove, Julien; Wang, Yan; Genestet, Charlotte; Trocme, Candice; Ahmadi, Mitra; Martin, Sandrine; Broisat, Alexis; Cretin, François; Ghezzi, Catherine; Polack, Benoit; Plumas, Joël; Toussaint, Bertrand

2013-01-01

The industrial development of active immunotherapy based on live-attenuated bacterial vectors has matured. We developed a microsyringe for antigen delivery based on the type III secretion system (T3SS) of P. aeruginosa. We applied the “killed but metabolically active” (KBMA) attenuation strategy to make this bacterial vector suitable for human use. We demonstrate that attenuated P. aeruginosa has the potential to deliver antigens to human antigen-presenting cells in vitro via T3SS with considerable attenuated cytotoxicity as compared with the wild-type vector. In a mouse model of cancer, we demonstrate that this KBMA strain, which cannot replicate in its host, efficiently disseminates into lymphoid organs and delivers its heterologous antigen. The attenuated strain effectively induces a cellular immune response to the cancerous cells while lowering the systemic inflammatory response. Hence, a KBMA P. aeruginosa microsyringe is an efficient and safe tool for in vivo antigen delivery. PMID:23531551

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.

Electronic Immunization Alerts and Spillover Effects on Other Preventive Care.

PubMed

Kim, Julia M; Rivera, Maria; Persing, Nichole; Bundy, David G; Psoter, Kevin J; Ghazarian, Sharon R; Miller, Marlene R; Solomon, Barry S

2017-08-01

The impact of electronic health record (EHR) immunization clinical alert systems on the delivery of other preventive services remains unknown. We assessed for spillover effects of an EHR immunization alert on delivery of 6 other preventive services, in children 18 to 30 months of age needing immunizations. We conducted a secondary data analysis, with additional primary data collection, of a randomized, historically controlled trial to improve immunization rates with EHR alerts, in an urban, primary care clinic. No significant differences were found in screening for anemia, lead, development, nutrition, and injury prevention counseling in children prompting EHR immunization alerts (n = 129), compared with controls (n = 135). Significant increases in oral health screening in patients prompting EHR alerts (odds ratio = 4.8, 95% CI = 1.8-13.0) were likely due to practice changes over time. An EHR clinical alert system targeting immunizations did not have a spillover effect on the delivery of other preventive services.

Hydroxyapatite-magnetite-MWCNT nanocomposite as a biocompatible multifunctional drug delivery system for bone tissue engineering.

PubMed

Pistone, Alessandro; Iannazzo, Daniela; Panseri, Silvia; Montesi, Monica; Tampieri, Anna; Galvagno, Signorino

2014-10-24

New magnetic hydroxyapatite-based nanomaterials as bone-specific systems for controlled drug delivery have been synthesized. The synthesized hydroxyapatite, HA, decorated with magnetite nanoparticles by a deposition method (HA/Fe3O4) and the nanocomposite system obtained using magnetic multi-walled carbon nanotubes (HA/MWCNT/Fe3O4) as a filler for HA have been characterized by chemical and morphological analyses, and their biological behavior was investigated. The systems have also been doped with clodronate in order to combine the effect of bone biomineralization induced by hydroxyapatite-based composites with the decrease of osteoclast formation induced by the drug. An analysis of the preosteoclastic RAW264.7 cell proliferation by MTT assay confirmed the high biocompatibility of the three systems. TRAP staining of RAW 264.7 conditioned with sRAKL to induce osteoclastogenesis, cultured in the presence of the systems doped and undoped with clodronate, showed the inhibitory effect of clodronate after we counted the MNC TRAP(+)cells but only in the osteoclast formation; in particular, the system HA/Fe3O4-Clo exerted a high inhibitory effect compared to the drug alone. These results demonstrate that the synthesized nanocomposites are a biocompatible magnetic drug delivery system and can represent a useful multimodal platform for applications in bone tissue engineering.

Norditropin NordiFlex® Device Compared to the Device Previously Used by Patients or Parents

ClinicalTrials.gov

2017-01-12

Growth Hormone Disorder; Growth Hormone Deficiency in Children; Foetal Growth Problem; Small for Gestational Age; Genetic Disorder; Turner Syndrome; Chronic Kidney Disease; Chronic Renal Insufficiency; Delivery Systems

Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

PubMed Central

Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A.; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E.

2014-01-01

This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables. PMID:24838219

Self-assembled mirror DNA nanostructures for tumor-specific delivery of anticancer drugs.

PubMed

Kim, Kyoung-Ran; Kim, Hyo Young; Lee, Yong-Deok; Ha, Jong Seong; Kang, Ji Hee; Jeong, Hansaem; Bang, Duhee; Ko, Young Tag; Kim, Sehoon; Lee, Hyukjin; Ahn, Dae-Ro

2016-12-10

Nanoparticle delivery systems have been extensively investigated for targeted delivery of anticancer drugs over the past decades. However, it is still a great challenge to overcome the drawbacks of conventional nanoparticle systems such as liposomes and micelles. Various novel nanomaterials consist of natural polymers are proposed to enhance the therapeutic efficacy of anticancer drugs. Among them, deoxyribonucleic acid (DNA) has received much attention as an emerging material for preparation of self-assembled nanostructures with precise control of size and shape for tailored uses. In this study, self-assembled mirror DNA tetrahedron nanostructures is developed for tumor-specific delivery of anticancer drugs. l-DNA, a mirror form of natural d-DNA, is utilized for resolving a poor serum stability of natural d-DNA. The mirror DNA nanostructures show identical thermodynamic properties to that of natural d-DNA, while possessing far enhanced serum stability. This unique characteristic results in a significant effect on the pharmacokinetics and biodistribution of DNA nanostructures. It is demonstrated that the mirror DNA nanostructures can deliver anticancer drugs selectively to tumors with enhanced cellular and tissue penetration. Furthermore, the mirror DNA nanostructures show greater anticancer effects as compared to that of conventional PEGylated liposomes. Our new approach provides an alternative strategy for tumor-specific delivery of anticancer drugs and highlights the promising potential of the mirror DNA nanostructures as a novel drug delivery platform. Copyright © 2016 Elsevier B.V. All rights reserved.

A palladium label to monitor nanoparticle-assisted drug delivery of a photosensitizer into tumor spheroids by elemental bioimaging.

PubMed

Niehoff, Ann-Christin; Moosmann, Aline; Söbbing, Judith; Wiehe, Arno; Mulac, Dennis; Wehe, Christoph A; Reifschneider, Olga; Blaske, Franziska; Wagner, Sylvia; Sperling, Michael; von Briesen, Hagen; Langer, Klaus; Karst, Uwe

2014-01-01

In this study, the cellular uptake of the second generation photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) was investigated using laser ablation coupled to inductively coupled plasma mass spectrometry (LA-ICP-MS) at a spatial resolution of 10 μm. To achieve high sensitivity, the photosensitizer was tagged with palladium. As a tumor model system, a 3D cell culture of the TKF-1 cell line was used. These tumor spheroids were incubated with the Pd-tagged photosensitizer embedded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles to investigate the efficiency of nanoparticle based drug delivery. An accumulation of the drug in the first cell layers of the tumor spheroid was observed. In the case of nanoparticle based drug delivery, a significantly more homogeneous distribution of the photosensitizer was achieved, compared to tumor spheroids incubated with the dissolved photosensitizer without the nanoparticular drug delivery system. The infiltration depth of the Pd-tagged photosensitizer could not be increased with rising incubation time, which can be attributed to the adsorption of the photosensitizer onto cellular components.

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

In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.

PubMed

Gourevich, Dana; Volovick, Alexander; Dogadkin, Osnat; Wang, Lijun; Mulvana, Helen; Medan, Yoav; Melzer, Andreas; Cochran, Sandy

2015-07-01

Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Multifunctional materials such as MCM-41÷Fe3O4÷folic acid as drug delivery system.

PubMed

Popescu, Simona; Ardelean, Ioana Lavinia; Gudovan, Dragoş; Rădulescu, Marius; Ficai, Denisa; Ficai, Anton; Vasile, Bogdan Ştefan; Andronescu, Ecaterina

2016-01-01

In this study, MCM-41 mesoporous silica nanoparticles (NPs) and MCM-41÷Fe3O4 mesoporous silica NPs were prepared by sol-gel method using CTAB (cetyltrimethylammonium bromide) as template and TEOS (tetraethyl orthosilicate) as silica precursor in order to use these materials as drug delivery system (DDS) for different biologically active agents. The MCM-41 and MCM-41÷Fe3O4 mesoporous silica NPs were characterized using specific physico-chemical methods [transmission electron microscopy (TEM), scanning electron microscopy (SEM), nitrogen adsorption and desorption studies - BET (Brunauer-Emmett-Teller) method, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy], while the release studies were done by a high-performance liquid chromatography (HPLC)-modified method. The pH dependence of the delivery of folic acid from the mesoporous structures was analyzed and found that the release is pH sensitive. The lower delivery at strongly acid pH comparing with neutral/slightly alkaline pH could be beneficial because in stomach the folic acid can be destroyed.

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…

Benchmarking as a Global Strategy for Improving Instruction in Higher Education.

ERIC Educational Resources Information Center

Clark, Karen L.

This paper explores the concept of benchmarking in institutional research, a comparative analysis methodology designed to help colleges and universities increase their educational quality and delivery systems. The primary purpose of benchmarking is to compare an institution to its competitors in order to improve the product (in this case…

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

PubMed

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

2014-01-01

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

Strength of primary care service delivery: a comparative study of European countries, Australia, New Zealand, and Canada.

PubMed

Pavlič, Danica R; Sever, Maja; Klemenc-Ketiš, Zalika; Švab, Igor; Vainieri, Milena; Seghieri, Chiara; Maksuti, Alem

2018-05-01

AimWe sought to examine strength of primary care service delivery as measured by selected process indicators by general practitioners from 31 European countries plus Australia, Canada, and New Zealand. We explored the relation between strength of service delivery and healthcare expenditures. The strength of a country's primary care is determined by the degree of development of a combination of core primary care dimensions in the context of its healthcare system. This study analyses the strength of service delivery in primary care as measured through process indicators in 31 European countries plus Australia, New Zealand, and Canada. A comparative cross-sectional study design was applied using the QUALICOPC GP database. Data on the strength of primary healthcare were collected using a standardized GP questionnaire, which included 60 questions divided into 10 dimensions related to process, structure, and outcomes. A total of 6734 general practitioners participated. Data on healthcare expenditure were obtained from World Bank statistics. We conducted a correlation analysis to analyse the relationship between strength and healthcare expenditures.FindingsOur findings show that the strength of service delivery parameters is less than optimal in some countries, and there are substantial variations among countries. Continuity and comprehensiveness of care are significantly positively related to national healthcare expenditures; however, coordination of care is not.

Amplitude gating for a coached breathing approach in respiratory gated 10 MV flattening filter‐free VMAT delivery

PubMed Central

Lee, Richard; Gete, Ermias; Duzenli, Cheryl

2015-01-01

The purpose of this study was to investigate amplitude gating combined with a coached breathing strategy for 10 MV flattening filter‐free (FFF) volumetric‐modulated arc therapy (VMAT) on the Varian TrueBeam linac. Ten patient plans for VMAT SABR liver were created using the Eclipse treatment planning system (TPS). The verification plans were then transferred to a CT‐scanned Quasar phantom and delivered on a TrueBeam linac using a 10 MV FFF beam and Varian's real‐time position management (RPM) system for respiratory gating based on breathing amplitude. Breathing traces were acquired from ten patients using two kinds of breathing patterns: free breathing and an interrupted (~5 s pause) end of exhale coached breathing pattern. Ion chamber and Gafchromic film measurements were acquired for a gated delivery while the phantom moved under the described breathing patterns, as well as for a nongated stationary phantom delivery. The gate window was set to obtain a range of residual target motion from 2–5 mm. All gated deliveries on a moving phantom have been shown to be dosimetrically equivalent to the nongated deliveries on a static phantom, with differences in point dose measurements under 1% and average gamma 2%/2 mm agreement above 98.7%. Comparison with the treatment planning system also resulted in good agreement, with differences in point‐dose measurements under 2.5% and average gamma 3%/3 mm agreement of 97%. The use of a coached breathing pattern significantly increases the duty cycle, compared with free breathing, and allows for shorter treatment times. Patients' free‐breathing patterns contain considerable variability and, although dosimetric results for gated delivery may be acceptable, it is difficult to achieve efficient treatment delivery. A coached breathing pattern combined with a 5 mm amplitude gate, resulted in both high‐quality dose distributions and overall shortest gated beam delivery times. PACS number: 87.55.Qr PMID:26219000

Polymersome-based drug-delivery strategies for cancer therapeutics

PubMed Central

Anajafi, Tayebeh; Mallik, Sanku

2015-01-01

Polymersomes are stable vesicles prepared from amphiphilic polymers and are more stable compared with liposomes. Although these nanovesicles have many attractive properties for in vitro/in vivo applications, liposome-based drug delivery systems are still prevalent in the market. In order to expedite the translational potential and to provide medically valuable formulations, the polymersomes need to be biocompatible and biodegradable. In this review, recent developments for biocompatible and biodegradable polymersomes, including the design of intelligent, targeted, and stimuli-responsive vesicles are summarized. PMID:25996048

Polymersome-based drug-delivery strategies for cancer therapeutics.

PubMed

Anajafi, Tayebeh; Mallik, Sanku

2015-01-01

Polymersomes are stable vesicles prepared from amphiphilic polymers and are more stable compared with liposomes. Although these nanovesicles have many attractive properties for in vitro/in vivo applications, liposome-based drug delivery systems are still prevalent in the market. In order to expedite the translational potential and to provide medically valuable formulations, the polymersomes need to be biocompatible and biodegradable. In this review, recent developments for biocompatible and biodegradable polymersomes, including the design of intelligent, targeted, and stimuli-responsive vesicles are summarized.

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...

A coordinated control strategy for insulin and glucagon delivery in type 1 diabetes.

PubMed

Herrero, Pau; Bondia, Jorge; Oliver, Nick; Georgiou, Pantelis

2017-10-01

Type 1 diabetes is an autoimmune condition characterised by a pancreatic insulin secretion deficit, resulting in high blood glucose concentrations, which can lead to micro- and macrovascular complications. Type 1 diabetes also leads to impaired glucagon production by the pancreatic α-cells, which acts as a counter-regulatory hormone to insulin. A closed-loop system for automatic insulin and glucagon delivery, also referred to as an artificial pancreas, has the potential to reduce the self-management burden of type 1 diabetes and reduce the risk of hypo- and hyperglycemia. To date, bihormonal closed-loop systems for glucagon and insulin delivery have been based on two independent controllers. However, in physiology, the secretion of insulin and glucagon in the body is closely interconnected by paracrine and endocrine associations. In this work, we present a novel biologically-inspired glucose control strategy that accounts for such coordination. An in silico study using an FDA-accepted type 1 simulator was performed to evaluate the proposed coordinated control strategy compared to its non-coordinated counterpart, as well as an insulin-only version of the controller. The proposed coordinated strategy achieves a reduction of hyperglycemia without increasing hypoglycemia, when compared to its non-coordinated counterpart.

Comparison of low-shear and high-shear granulation processes: effect on implantable calcium phosphate granule properties.

PubMed

Chevalier, E; Viana, M; Cazalbou, S; Chulia, D

2009-10-01

Calcium phosphate porous ceramics present a great interest not only as complex bone defect fillers but also as drug delivery systems. Most of the methods described in the literature to fabricate pellets are based on compaction, casting into spherical molds, or on processes such as liquid immiscibility or foaming. Despite wet granulation is used in a wide range of applications in pharmaceuticals, food, detergents, fertilizers, and minerals, it is not applied in the biomaterial field to produce granules. In this study physicochemical and in vitro drug delivery properties of implantable calcium phosphate granules, produced by two wet agglomeration processes, were compared. Pellets obtained by high shear granulation (granulation in a Mi-Pro apparatus) were shown to be more spherical and less friable than granules elaborated by low shear process (granulation in a Kenwood apparatus). Although Mi-Pro pellets had a slightly lower porosity compared to Kenwood granules, ibuprofen loading efficiency and dissolution profiles were not statistically different and the release mechanism was mainly controlled by diffusion, in both cases. Mi-Pro pellets appeared to be better candidates as bone defect fillers and local drug delivery systems as far as they were more spherical and less friable than Kenwood agglomerates.

Development of a sustained fluoride delivery system.

PubMed

Baturina, Olga; Tufekci, Eser; Guney-Altay, Ozge; Khan, Shadeed M; Wnek, Gary E; Lindauer, Steven J

2010-11-01

To develop a novel delivery system by which fluoride incorporated into elastomeric rings, such as those used to ligate orthodontic wires, will be released in a controlled and constant manner. Polyethylene co-vinyl acetate (PEVA) was used as the model elastomer. Samples (N = 3) were prepared by incorporating 0.02 to 0.4 g of sodium fluoride (NaF) into previously prepared PEVA solution. Another group of samples prepared in the same manner were additionally dip-coated in PEVA to create an overcoat. Fluoride release studies were conducted in vitro using an ion selective electrode over a period of 45 days. The amount of fluoride released was compared to the optimal therapeutic dose of 0.7 microg F(-)/ring/d. Only coated samples with the highest fluoride content (group D, 0.4 g of NaF) were able to release fluoride at therapeutic levels. When fluoride release from coated and uncoated samples with the same amount of NaF were compared, it was shown that the dip-coating technique resulted in a fluoride release in a controlled manner while eliminating the initial burst effect. This novel fluoride delivery matrix provided fluoride release at a therapeutically effective rate and profile.

Comparison of exosomes and ferritin protein nanocages for the delivery of membrane protein therapeutics.

PubMed

Cho, Eunji; Nam, Gi-Hoon; Hong, Yeonsun; Kim, Yoon Kyoung; Kim, Dong-Hwee; Yang, Yoosoo; Kim, In-San

2018-06-10

Exosomes are small membrane vesicles secreted by most cell types that play an important role in intercellular communication. Due to the characteristic of transferring their biomacromolecules, exosomes have potential as a new alternative for delivering protein therapeutics. Here, we investigate whether exosomes provide crucial advantages over other nanoparticles, in particular protein nanocage formulations, as a delivery system for membrane protein therapeutics. We characterized membrane-scaffold-based exosomes and protein-scaffold-based ferritin nanocages, both harboring SIRPα (signal regulatory protein α), an antagonist of CD47 on tumor cells. The efficacy of these two systems in delivering protein therapeutics was compared by testing their ability to enhance phagocytosis of tumor cells by bone-marrow-derived macrophages and subsequent inhibition of in vivo tumor growth. These analyses allowed us to comprehensively conclude that the therapeutic index of exosome-mediated CD47 blockade against tumor growth inhibition was higher than that of the same dose of ferritin-SIRPα. The results of this analysis reveal the importance of the unique characteristics of exosomes, in particular their membrane scaffold, in improving therapeutic protein delivery compared with protein-scaffold-based nanocages. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed Central

Sharma, Anupriya; Ramesh, Amitha; Thomas, Biju

2009-01-01

Background and Objectives: Circulating C-reactive protein (CRP) levels are a marker of systemic inflammation and are associated with periodontal disease, a chronic bacterial infection associated with elevation of proinflammatory cytokines and prostaglandins. CRP has been associated with adverse pregnancy outcomes, including preterm delivery, preeclampsia, and intrauterine growth restriction. Furthermore, periodontal disease has been associated with increased risk of preterm low birth weight, low birth weight, and preterm birth. The present study was conducted to assess plasma CRP levels in pregnant women with and without periodontal disease; to evaluate the effect of periodontal therapy on the incidence of preterm delivery; and to compare the incidence of preterm delivery in pregnant women with and without periodontal disease. Materials and Methods: A total of 90 pregnant women aged between 18-35 years with gestational age between 12-28 weeks were recruited and divided into three equal groups (control group, study group, treatment group) of 30 each. Blood samples were taken for estimation of C-reactive protein levels from all groups at 12-20 weeks of gestation, determined using ultrasensitive turbidimetric immunoassay (QUANTIA-CRP US). The treatment group comprised plaque control, scaling, and root planning and daily rinsing with 0.2% chlorhexidine mouth before 28 weeks of gestation. Results: The mean value of C-reactive protein levels in subjects with periodontal disease was higher compared to control group i.e., 1.20 ± 0.247 mg/dl and 1.22 ± 0.250 mg/dl, respectively, compared to 0.713 ± 0.139 mg/ dl (P = 0.001). The mean value of CRP levels before treatment was greater than the mean value after treatment i.e., 1.22 ± 0.25 compared to 0.84 ± 0.189 (P < 0.001). The incidence of preterm delivery (< 37 weeks) was 31.7% in the periodontal disease group (study group) compared to 8.3% in the control group (P = 0.001). The incidence of preterm delivery in the treatment group was 15.0% compared to 31.7% in the nontreatment group (study group). Conclusion: The findings from the study suggest that periodontal disease in pregnant women is associated with increased C- reactive protein levels in early pregnancy, incidence of preterm delivery is higher in pregnant women with periodontal disease compared to healthy controls, periodontal therapy during pregnancy reduces plasma CRP levels and there is decrease in incidence of preterm delivery after periodontal therapy. PMID:20379412

Cell-based delivery of oncolytic viruses: a new strategic alliance for a biological strike against cancer.

PubMed

Power, Anthony T; Bell, John C

2007-04-01

Recent years have seen tremendous advances in the development of exquisitely targeted replicating virotherapeutics that can safely destroy malignant cells. Despite this promise, clinical advancement of this powerful and unique approach has been hindered by vulnerability to host defenses and inefficient systemic delivery. However, it now appears that delivery of oncolytic viruses within carrier cells may offer one solution to this critical problem. In this review, we compare the advantages and limitations of the numerous cell lineages that have been investigated as delivery platforms for viral therapeutics, and discuss examples showing how combined cell-virus biotherapeutics can be used to achieve synergistic gains in antitumor activity. Finally, we highlight avenues for future preclinical research that might be taken in order to refine cell-virus biotherapeutics in preparation for human trials.

Fluoride concentrations in urine of delivery ward personnel following exposure to low concentrations of methoxyflurane.

PubMed

Dahlgren, B E

1979-09-01

Midwives and other delivery ward personnel exposed to methoxyflurane do not have measurable traces of the agent in expired air when examined soon after exposure. This may imply a rapid uptake of the anesthetic. If this is the case, then the products of the metabolism of methoxyflurane, such as fluoride, may appear in the urine of such personnel. The present study investigated urinary fluoride levels in 24 delivery ward personnel and compared the values found after methoxyflurane/nitrous oxide analgesia with those measured in the same individuals after exposure to nitrous oxide alone. A highly significant difference was observed. Thus it would appear that, in spite of an apparently adequate system of environmental ventilation, there is a significant uptake of methoxyflurane by delivery ward personnel when this agent is employed for obstetrical analgesia.

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.

Comparison of Free-Beam- and Fiber-Type CO2 Laser Delivery Systems in Stapes Surgery.

PubMed

Chang, Mun Young; Choi, Hyun Seok; Lee, Sang-Youp; Koo, Ja-Won

2017-07-01

A free-beam-type CO 2 laser, which use a micromanipulator mounted on a microscope as the delivery system, has the merit of not being affected by hand tremor at the time of shooting. However, this delivery system has several disadvantages, including a restricted operation range and a risk of incorrect focusing. A fiber-type CO 2 laser uses a hand-held delivery system and has the opposite merits and demerits. We compared the results of stapes surgery with free-beam and fiber type delivery systems. The study enrolled 36 patients who underwent stapedotomy with free-beam- (n=26) or fiber- (n=10) type CO 2 lasers. The air-bone (AB) gap closure, bone conduction (BC) change, and operating time were evaluated. The AB gap closure was calculated by subtracting the preoperative BC thresholds from the postoperative air conduction thresholds. The BC change was calculated by subtracting the postoperative BC thresholds from the preoperative BC thresholds. The mean operating time was significantly ( p =0.035) shorter in the fiber-type group (72.5±8.2 min) than in the free-beam-type group (80.5±11.4 min). The mean AB gap closure did not differ significantly ( p =0.297) between the free-beamand fiber-type groups (5.8±10.1 and 1.4±6.8 dB, respectively). The mean BC change did not differ significantly ( p =0.873) between the free-beam- and fiber-type groups (2.4±6.9 and 2.8±5.3 dB, respectively). The hearing outcomes did not differ significantly between the two groups. Operating times were significantly shorter using the fiber-type CO 2 laser, while hearing outcomes did not differ significantly between the two groups.

Camptothecin-loaded fusogenic nanodroplets as ultrasound theranostic agent in stem cell-mediated drug-delivery system.

PubMed

Ho, Yi-Ju; Chiang, Yu-Jung; Kang, Shih-Tsung; Fan, Ching-Hsiang; Yeh, Chih-Kuang

2018-05-28

Adipose-derived stem cells (ADSCs) have been utilized in cellular delivery systems to carry therapeutic agents into tumors by migration. Drug-loaded nanodroplets release drugs and form bubbles after acoustic droplet vaporization (ADV) triggered by ultrasound stimulation, providing a system for ultrasound-induced cellular delivery of theranostic agents. In order to improve the efficiency of drug release, fusogenic nanodroplets were designed to go from nano to micron size upon uptake by ADSCs for reducing ADV threshold. The purpose of our study was to demonstrate the utility of camptothecin-loaded fusogenic nanodroplets (CPT-FNDs) as ultrasound theranostic agents in an ADSCs delivery system. CPT-FNDs showed an increase in size from 81.6 ± 3.5 to 1043.5 ± 28.3 nm and improved CPT release from 22.0 ± 1.8% to 37.6 ± 2.1%, demonstrating the fusion ability of CPT-FNDs. CPT-FNDs-loaded ADSCs demonstrated a cell viability of 77 ± 4%, and the in vitro migration ability was 3.2 ± 1.2-fold for the tumor condition compared to the cell growth condition. Ultrasound enhancement imaging showed intratumoral ADV-generated bubble formation (increasing 3.24 ± 0.47 dB) triggered by ultrasound after CPT-FNDs-loaded ADSCs migration into B16F0 tumors. Histological images revealed intratumoral distribution of CPT-FNDs-loaded ADSCs and tissue damage due to the ADV. The CPT-FNDs can be used as theranostic agents in an ADSCs delivery system to provide the ultrasound contrast imaging and deliver combination therapy of drug release and physical damage after ADV. Copyright © 2018 Elsevier B.V. All rights reserved.

Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment.

PubMed

Zhang, Wen; Li, Changzheng; Shen, Chengwu; Liu, Yuguo; Zhao, Xiaoting; Liu, Ying; Zou, Dongna; Gao, Zhenfa; Yue, Chunwen

2016-09-01

Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers. This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues. In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. The in vitro and in vivo anti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line. PTX/CBP NPs achieved the highest cytotoxic effect among all formulations in vitro, as compared with single drug delivery NPs. In vivo investigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity. The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy.

[Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum].

PubMed

Sun, Yi-Yi; Ll, Tong-Hui; Tang, Chen-Kang; Zhu, Zi-Ping; Chi, Qun; Hou, Shi-Xiang

2005-06-01

To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity. BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection. The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

Changes in Quality of Health Care Delivery after Vertical Integration

PubMed Central

Carlin, Caroline S; Dowd, Bryan; Feldman, Roger

2015-01-01

Objectives To fill an empirical gap in the literature by examining changes in quality of care measures occurring when multispecialty clinic systems were acquired by hospital-owned, vertically integrated health care delivery systems in the Twin Cities area. Data Sources/Study Setting Administrative data for health plan enrollees attributed to treatment and control clinic systems, merged with U.S. Census data. Study Design We compared changes in quality measures for health plan enrollees in the acquired clinics to enrollees in nine control groups using a differences-in-differences model. Our dataset spans 2 years prior to and 4 years after the acquisitions. We estimated probit models with errors clustered within enrollees. Data Collection/Extraction Methods Data were assembled by the health plan’s informatics team. Principal Findings Vertical integration is associated with increased rates of colorectal and cervical cancer screening and more appropriate emergency department use. The probability of ambulatory care–sensitive admissions increased when the acquisition caused disruption in admitting patterns. Conclusions Moving a clinic system into a vertically integrated delivery system resulted in limited increases in quality of care indicators. Caution is warranted when the acquisition causes disruption in referral patterns. PMID:25529312

Biomimetic design in microparticulate vaccines.

PubMed

Keegan, Mark E; Whittum-Hudson, Judith A; Mark Saltzman, W

2003-11-01

Current efforts to improve the effectiveness of microparticle vaccines include incorporating biomimetic features into the particles. Many pathogens use surface molecules to target specific cell types in the gut for host invasion. This observation has inspired efforts to chemically conjugate cell-type targeting ligands to the surfaces of microparticles in order to increase the efficiency of uptake, and therefore the effectiveness, of orally administered microparticles. Bio-mimicry is not limited to the exterior surface of the microparticles. Anti-idiotypic antibodies, cytokines or other biological modifiers can be encapsulated for delivery to sites of interest as vaccines or other therapeutics. Direct mucosal delivery of microparticle vaccines or immunomodulatory agents may profoundly enhance mucosal and systemic immune responses compared to other delivery routes.

Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

PubMed Central

Kalomiraki, Marina; Thermos, Kyriaki; Chaniotakis, Nikos A

2016-01-01

Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. PMID:26730187

Analysing Costs/Benefits for Distance Education Programmes. Knowledge Series: A Topical, Start-Up Guide to Distance Education Practice and Delivery.

ERIC Educational Resources Information Center

Rumble, Greville

Cost analysis makes it possible to establish how much things costs, set budgets, determine prices, and compare the costs of different options. In distance education (DE), the main areas of cost analysis are as follows: print-based correspondence systems; educational/institutional television and radio systems; multimedia systems, and e-education…

A novel application of maleimide for advanced drug delivery: in vitro and in vivo evaluation of maleimide-modified pH-sensitive liposomes.

PubMed

Li, Tianshu; Takeoka, Shinji

2013-01-01

Maleimide is a stable and easy-to-handle moiety that rapidly and covalently conjugates thiol groups of cysteine residues in proteins or peptides. Herein, we use maleimide to modify the surface of liposomes in order to obtain an advanced drug delivery system. Employing a small amount (0.3 mol%) of maleimide-polyethylene glycol (PEG) to modify the surface of the liposomes M-GGLG-liposomes, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG)/cholesterol/poly(ethylene glycol) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG5000-DSPE)/maleimide-PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03, drug delivery efficiency was remarkably improved both in vitro and in vivo compared to unmodified liposomes (GGLG-liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03). Moreover, this modification did not elicit any detectable increase in cytotoxicity. The maleimide-modification did not alter the physical characteristics of the liposomes such as size, zeta potential, pH sensitivity, dispersibility and drug encapsulation efficiency. However, M-GGLG-liposomes were more rapidly (≥2-fold) internalized into HeLa, HCC1954, and MDA-MB-468 cells compared to GGLG-liposomes. In vivo, M-GGLG-liposomes encapsulating doxorubicin (M-GGLG-DOX-liposomes) also showed a more potent antitumor effect than GGLG-DOX-liposomes and the widely used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-DOX-liposomes after two subcutaneous injections around breast cancer tissue in mice. The biodistribution of liposomes in this model was observed using an in vivo imaging system, which showed that M-GGLG-liposomes were present for significantly longer at the injection site compared to GGLG-liposomes. The outstanding biological functions of the maleimide-modified liposomes as a novel drug delivery system make them ideally suited to a wide range of applications.

A novel application of maleimide for advanced drug delivery: in vitro and in vivo evaluation of maleimide-modified pH-sensitive liposomes

PubMed Central

Li, Tianshu; Takeoka, Shinji

2013-01-01

Maleimide is a stable and easy-to-handle moiety that rapidly and covalently conjugates thiol groups of cysteine residues in proteins or peptides. Herein, we use maleimide to modify the surface of liposomes in order to obtain an advanced drug delivery system. Employing a small amount (0.3 mol%) of maleimide-polyethylene glycol (PEG) to modify the surface of the liposomes M-GGLG-liposomes, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG)/cholesterol/poly(ethylene glycol) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG5000-DSPE)/maleimide-PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03, drug delivery efficiency was remarkably improved both in vitro and in vivo compared to unmodified liposomes (GGLG-liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03). Moreover, this modification did not elicit any detectable increase in cytotoxicity. The maleimide-modification did not alter the physical characteristics of the liposomes such as size, zeta potential, pH sensitivity, dispersibility and drug encapsulation efficiency. However, M-GGLG-liposomes were more rapidly (≥2-fold) internalized into HeLa, HCC1954, and MDA-MB-468 cells compared to GGLG-liposomes. In vivo, M-GGLG-liposomes encapsulating doxorubicin (M-GGLG-DOX-liposomes) also showed a more potent antitumor effect than GGLG-DOX-liposomes and the widely used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-DOX-liposomes after two subcutaneous injections around breast cancer tissue in mice. The biodistribution of liposomes in this model was observed using an in vivo imaging system, which showed that M-GGLG-liposomes were present for significantly longer at the injection site compared to GGLG-liposomes. The outstanding biological functions of the maleimide-modified liposomes as a novel drug delivery system make them ideally suited to a wide range of applications. PMID:24143089

Investigation of Fragment Antibody Stability and Its Release Mechanism from Poly(Lactide-co-Glycolide)-Triacetin Depots for Sustained-Release Applications.

PubMed

Chang, Debby P; Garripelli, Vivek Kumar; Rea, Jennifer; Kelley, Robert; Rajagopal, Karthikan

2015-10-01

Achieving long-term drug release from polymer-based delivery systems continues to be a challenge particularly for the delivery of large hydrophilic molecules such as therapeutic antibodies and proteins. Here, we report on the utility of an in situ-forming and injectable polymer-solvent system for the long-term release of a model antibody fragment (Fab1). The delivery system was prepared by dispersing a spray-dried powder of Fab1 within poly(lactide-co-glycolide) (PLGA)-triacetin solution. The formulation viscosity was within the range 1.0 ± 0.3 Pa s but it was injectable through a 27G needle. The release profile of Fab1, measured in phosphate-buffered saline (PBS), showed a lag phase followed by sustained-release phase for close to 80 days. Antibody degradation during its residence within the depot was comparable to its degradation upon long-term incubation in PBS. On the basis of temporal changes in surface morphology, stiffness, and depot mass, a mechanism to account for the drug release profile has been proposed. The unprecedented release profile and retention of greater than 80% of antigen-binding capacity even after several weeks demonstrates that PLGA-triacetin solution could be a promising system for the long-term delivery of biologics. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Numerical modelling of transdermal delivery from matrix systems: parametric study and experimental validation with silicone matrices.

PubMed

Snorradóttir, Bergthóra S; Jónsdóttir, Fjóla; Sigurdsson, Sven Th; Másson, Már

2014-08-01

A model is presented for transdermal drug delivery from single-layered silicone matrix systems. The work is based on our previous results that, in particular, extend the well-known Higuchi model. Recently, we have introduced a numerical transient model describing matrix systems where the drug dissolution can be non-instantaneous. Furthermore, our model can describe complex interactions within a multi-layered matrix and the matrix to skin boundary. The power of the modelling approach presented here is further illustrated by allowing the possibility of a donor solution. The model is validated by a comparison with experimental data, as well as validating the parameter values against each other, using various configurations with donor solution, silicone matrix and skin. Our results show that the model is a good approximation to real multi-layered delivery systems. The model offers the ability of comparing drug release for ibuprofen and diclofenac, which cannot be analysed by the Higuchi model because the dissolution in the latter case turns out to be limited. The experiments and numerical model outlined in this study could also be adjusted to more general formulations, which enhances the utility of the numerical model as a design tool for the development of drug-loaded matrices for trans-membrane and transdermal delivery. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

PubMed Central

Ko, Young Tag; Choi, Dong-Kug

2018-01-01

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

Rural and urban transit district benchmarking : effectiveness and efficiency guidance document.

DOT National Transportation Integrated Search

2011-05-01

Rural and urban transit systems have sought ways to compare performance across agencies, : identifying successful service delivery strategies and applying these concepts to achieve : successful results within their agency. Benchmarking is a method us...

Comparative evaluation of surface and downhole steam-generation techniques

NASA Astrophysics Data System (ADS)

Hart, C.

The application of heat to reservoirs containing high API gravity oils can substantially improve recovery. Although steam injection is currently the principal thermal recovery method, heat transmission losses associated with delivery of the steam from the surface generators to the oil bearing formation has limited conventional steam injection to shallow reservoirs. The objective of the Department of Energy's Project DEEP STEAM is to develop the technology required to economically produce heavy oil from deep reservoirs. The tasks included in this effort are the development and evaluation of thermally efficient delivery systems and downhole steam generation systems. The technical and economic performance of conventional surface steam drives, which are strongly influenced by heat losses are compared. The selection of a preferred technology based upon either total efficiency or cost is found to be strongly influenced by reservoir depth, steam mass flow rate, and sandface steam quality.

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

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.

Myocardial gene delivery using molecular cardiac surgery with recombinant adeno-associated virus vectors in vivo

PubMed Central

White, JD; Thesier, DM; Swain, JBD; Katz, MG; Tomasulo, C; Henderson, A; Wang, L; Yarnall, C; Fargnoli, A; Sumaroka, M; Isidro, A; Petrov, M; Holt, D; Nolen-Walston, R; Koch, WJ; Stedman, HH; Rabinowitz, J; Bridges, CR

2013-01-01

We use a novel technique that allows for closed recirculation of vector genomes in the cardiac circulation using cardiopulmonary bypass, referred to here as molecular cardiac surgery with recirculating delivery (MCARD). We demonstrate that this platform technology is highly efficient in isolating the heart from the systemic circulation in vivo. Using MCARD, we compare the relative efficacy of single-stranded (ss) adeno-associated virus (AAV)6, ssAAV9 and self-complimentary (sc)AAV6-encoding enhanced green fluorescent protein, driven by the constitutive cytomegalovirus promoter to transduce the ovine myocardium in situ. MCARD allows for the unprecedented delivery of up to 48 green fluorescent protein genome copies per cell globally in the sheep left ventricular (LV) myocardium. We demonstrate that scAAV6-mediated MCARD delivery results in global, cardiac-specific LV gene expression in the ovine heart and provides for considerably more robust and cardiac-specific gene delivery than other available delivery techniques such as intramuscular injection or intracoronary injection; thus, representing a potential, clinically translatable platform for heart failure gene therapy. PMID:21228882

Enhanced thermogenic program by non-viral delivery of combinatory browning genes to treat diet-induced obesity in mice.

PubMed

Park, Hongsuk; Cho, Sungpil; Janat-Amsbury, Margit M; Bae, You Han

2015-12-01

Thermogenic program (also known as browning) is a promising and attractive anti-obesity approach. Islet amyloid polypeptide (IAPP) and irisin have emerged as potential browning hormones that hold high potential to treat obesity. Here, we have constructed a dual browning gene system containing both IAPP and irisin (derived from fibronectin type III domain containing 5; FNDC5) combined with 2A and furin self-cleavage sites. Intraperitoneal administration of the construct complexed with a linear polyethylenimine into diet-induced obese mice demonstrated the elevation of anti-obesogenic effects characterized as the decreased body weight, adiposity, and levels of glucose and insulin. In addition, the construct delivery increased energy expenditure and the expression of core molecular determinants associated with browning. The additional advantages of the dual browning gene construct delivery compared to both single gene construct delivery and dual peptide delivery can be emphasized on efficacy and practicability. Hence, we have concluded that dual browning gene delivery makes it therapeutically attractive for diet-induced obesity treatment. Copyright © 2015 Elsevier Ltd. 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.

Targeted killing of cancer cells in vivo and in vitro with IGF-IR antibody-directed carbon nanohorns based drug delivery.

PubMed

Li, Nannan; Zhao, Qian; Shu, Chang; Ma, Xiaona; Li, Ruixin; Shen, Hongjun; Zhong, Wenying

2015-01-30

Oxidized single-wall carbon nanohorns (oxSWNHs) have shown great potential in drug delivery. The purpose of this study was to design an effective targeted drug delivery system (DDS) based on oxSWNHs, which could carry high dose of drug to tumor sites and improve the therapeutic efficacy with less adverse effects. OxSWNHs incorporated the anticancer drug vincristine (VCR) via physical adsorption, then wrapped DSPE-PEG-IGF-IR monoclonal antibody (mAb) through an amide liker to obtain the drug delivery system, VCR@oxSWNHs-PEG-mAb. The in vitro release behavior study indicated that the DDS had good sustained release and the cumulative release of VCR was 80% at 144h. Compared with free VCR, the tumor targeting drug delivery efficiently enhanced the cytotoxicity in cultured MCF-7 cells in vitro, and afforded higher antitumor efficacy without obvious toxic effects to normal organs in tumor mice in vivo. In addition, the targeted DDS could reduce the toxicity of VCR to the living mice. This study demonstrated that VCR@oxSWNHs-PEG-mAb might be promising for high treatment efficacy with minimal side effects in future cancer therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Local application of an ibandronate/collagen sponge improves femoral fracture healing in ovariectomized rats

PubMed Central

Liu, Yansong; Hou, Zhiyong; Chen, Wei; Jin, Lin; Tian, Ye; Ju, Linlin; Liu, Bo; Dong, Tianhua; Zhang, Fei

2017-01-01

Non-union is a major clinical problem in the healing of fractures, especially in patients with osteoporosis. The systemic administration of drugs is time consuming and large doses are demanding and act slowly, whereas local release acts rapidly, increases the quality and quantity of the bone tissue. We hypothesize that local delivery demonstrates better therapeutic effects on an osteoporotic fracture. The aim of this paper is to investigate the effect of the local application of ibandronate loaded with a collagen sponge on regulating bone formation and remodeling in an osteoporotic rat model of fracture healing. We found that the local delivery of ibandronate exhibited excellent effects on improving the bone microarchitecture and suppressed effects on bone remodeling. At 4 weeks, more callus formation and improvement of mechanical character and microstructure were observed in a local delivery via μCT, mechanical test, histological research and serum analysis. The suppression of bone remodeling was compared with a systemic treatment at 12 weeks, and the structural mechanical properties and microarchitecture were also improved with local delivery. This research identifies an earlier, safer and integrated approach for local delivery of ibandronate with collagen and provides a better strategy for the treatment of osteoporotic fracture in rats. PMID:29108027

Pharmacokinetics and anti-hypertensive effect of metoprolol tartrate rectal delivery system.

PubMed

Abou el Ela, Amal El Sayeh F; Allam, Ayat A; Ibrahim, Ehsan H

2016-01-01

The main aim of this work was to develop rectal suppositories for better delivery of metoprolol tartrate (MT). The various bases used were fatty, water soluble and emulsion bases. The physical properties of the prepared suppositories were characterized such as weight variation, hardness, disintegration time, melting range and the drug content uniformity. The in vitro release of MT from the prepared suppositories was carried out. The evaluation of the pharmacological effects of MT on the blood pressure and heart rate of the healthy rabbits after the rectal administration compared to the oral tablets was studied. Moreover, the formulation with the highest in vitro release and the highest pharmacological effects would be selected for a further pharmacokinetics study compared to the oral tablets. The results revealed that the emulsion bases gave the highest rate of the drug release than the other bases used. The reduction effect of the emulsion MT suppository base on the blood pressure and heart rate was found to be faster and greater than that administered orally. The selected emulsion suppository base (F11) showed a significant increase in the AUC (1.88-fold) in rabbits as compared to the oral tablets. From the above results we can conclude that rectal route can serve as an efficient alternative route to the oral one for systemic delivery of MT which may be due to the avoidance of first-pass effect in the liver.

Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

PubMed

Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

2017-05-01

In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

A preliminary assessment of two hospital food service systems using parameters of food safety and consumer opinion.

PubMed

Hartwell, H; Edwards, J S

2001-12-01

The goal of any hospital caterer should be to provide food that meets nutritional requirements, satisfies the patient, improves morale and is microbiologically safe. Food distribution to hospital wards plays a critical role. The aim of this study was to compare two hospital food service systems using parameters of food safety and consumer opinion. An NHS hospital was selected where food delivery was due to change from a plated system to a cafeteria trolley system. Samples (50 g) of dishes (n = 27) considered to be high-risk were collected for three consecutive days from breakfast, lunch and supper meals. The samples were taken from a pre-ordered tray (similar to that of a patient) in the plated system and from the trolley on the ward in the cafeteria system of meal delivery (approximately six months after its introduction). Consumer opinions cards (n = 180) were distributed and interviews also conducted. Microbiologically, the quality of food items delivered by both systems was satisfactory. However, concern was raised with the plated system, not for hot foods cooling down but for chilled foods warming up and being sustained in ambient conditions. Overall consumer satisfaction and experience was enhanced with the trolley system. Food was hotter and generally perceived to be of a better quality. Satisfaction with cold desserts was not dependent on the delivery system.

Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

PubMed

Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

2017-05-19

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

[Polyelectrolyte microcapsules as systems for delivery of biologically active substances].

PubMed

Borodina, T N; Rumsh, L D; Kunizhev, S M; Sukhorukov, G B; Vorozhtsov, G N; Fel'dman, B M; Markvicheva, E A

2007-01-01

Novel biodegradable microcapsules for delivery of biologically active substances (BAS) were prepared by layer-by-layer (LbL) adsorption of oppositely charged polyelectrolytes, namely sodium alginate (Alg) and poly-L-lysine (PLL). To immobilize these BAS, porous spherical CaCO3 microparticles were used as templates. The templates (cores) were coated with several layers of oppositely charged polyelectrolytes forming shell on a core surface. The core-shell microparticles were converted into hollow microcapsules by a core dissolution after an EDTA treatment. Mild conditions for microcapsule fabrication allow to perform an entrapment of various biomolecules while keeping their bioactivity. Biocompatibility and biodegradable capability of the polyelectrolytes give a possibility to use the microcapsules as the target delivery systems. Chymotrypsin (Chym) entrapped into the microcapsules was used as a model enzyme. The immobilized enzyme was found to keep about 86% of the activity compared to a native Chym. The obtained microcapsules were stable at an acidic medium while they could be easily decomposed by trypsin treatment at an slightly alkaline medium. Chym was shown to be active after being released from the microcapsules decomposed by trypsin treatment. Thus, the microcapsules prepared by the LbL - technique can be used for the development of new type of BAS delivery systems in humans and animals.

Controlled-release systemic delivery - a new concept in cancer chemoprevention

PubMed Central

2012-01-01

Many chemopreventive agents have encountered bioavailability issues in pre-clinical/clinical studies despite high oral doses. We report here a new concept utilizing polycaprolactone implants embedded with test compounds to obtain controlled systemic delivery, circumventing oral bioavailability issues and reducing the total administered dose. Compounds were released from the implants in vitro dose dependently and for long durations (months), which correlated with in vivo release. Polymeric implants of curcumin significantly inhibited tissue DNA adducts following the treatment of rats with benzo[a]pyrene, with the total administered dose being substantially lower than typical oral doses. A comparison of bioavailability of curcumin given by implants showed significantly higher levels of curcumin in the plasma, liver and brain 30 days after treatment compared with the dietary route. Withaferin A implants resulted in a nearly 60% inhibition of lung cancer A549 cell xenografts, but no inhibition occurred when the same total dose was administered intraperitoneally. More than 15 phytochemicals have been tested successfully by this formulation. Together, our data indicate that this novel implant-delivery system circumvents oral bioavailability issues, provides continuous delivery for long durations and lowers the total administered dose, eliciting both chemopreventive/chemotherapeutic activities. This would also allow the assessment of activity of minor constituents and synthetic metabolites, which otherwise remain uninvestigated in vivo. PMID:22696595

A Review of Intra- and Extracellular Antigen Delivery Systems for Virus Vaccines of Finfish

PubMed Central

Munang'andu, Hetron Mweemba; Evensen, Øystein

2015-01-01

Vaccine efficacy in aquaculture has for a long time depended on evaluating relative percent survival and antibody responses after vaccination. However, current advances in vaccine immunology show that the route in which antigens are delivered into cells is deterministic of the type of adaptive immune response evoked by vaccination. Antigens delivered by the intracellular route induce MHC-I restricted CD8+ responses while antigens presented through the extracellular route activate MHC-II restricted CD4+ responses implying that the route of antigen delivery is a conduit to induction of B- or T-cell immune responses. In finfish, different antigen delivery systems have been explored that include live, DNA, inactivated whole virus, fusion protein, virus-like particles, and subunit vaccines although mechanisms linking these delivery systems to protective immunity have not been studied in detail. Hence, in this review we provide a synopsis of different strategies used to administer viral antigens via the intra- or extracellular compartments. Further, we highlight the differences in immune responses induced by antigens processed by the endogenous route compared to exogenously processed antigens. Overall, we anticipate that the synopsis put together in this review will shed insights into limitations and successes of the current vaccination strategies used in finfish vaccinology. PMID:26065009

Non-traditional vs. Traditional Academic Delivery Systems: Comparing ETS Scores for Undergraduate Students in Business Programs, 1996-1999. AIR 1999 Annual Forum Paper.

ERIC Educational Resources Information Center

Jonas, Peter M.; Weimer, Don

This two-year study involving five colleges and universities compared the academic achievement, as measured by the Educational Testing Service (ETS) Major Field Achievement Test (MFAT) in Business of students in traditional undergraduate programs and those in non-traditional accelerated adult degree programs. The study also compared the subjects'…

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

On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl.

PubMed

Shin, Soo Hyeon; Ghosh, Priyanka; Newman, Bryan; Hammell, Dana C; Raney, Sam G; Hassan, Hazem E; Stinchcomb, Audra L

2017-09-01

At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The J max enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p < 0.05) among the three fentanyl TDSs. The J max enhancement ratios due to transient heat exposure were significantly different for the two nicotine TDSs, but not for the three fentanyl TDSs. Furthermore, the transient heat exposure affected the clearance of drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.

Comparison across Three Hybrid Lipid-Based Drug Delivery Systems for Improving the Oral Absorption of the Poorly Water-Soluble Weak Base Cinnarizine.

PubMed

Joyce, Paul; Yasmin, Rokhsana; Bhatt, Achal; Boyd, Ben J; Pham, Anna; Prestidge, Clive A

2017-11-06

Three state-of-the-art drug delivery vehicles engineered by nanostructuring lipid colloids within solid particle matrices were fabricated for the oral delivery of the poorly water-soluble, weak base, cinnarizine (CIN). The lipid and solid phase of each formulation was varied to systematically analyze the impact of key material characteristics, such as nanostructure and surface chemistry, on the in vitro and in vivo fate of CIN. The three systems formulated were: silica-stabilized lipid cubosomes (SSLC), silica-solid lipid hybrid (SSLH), and polymer-lipid hybrid (PLH) particles. Significant biopharmaceutical advantages were presented for CIN when solubilized in the polymer (poly(lactic-co-glycolic) acid; PLGA) and lipid phase of PLH particles compared to the lipid phases of SSLC and SSLH particles. In vitro dissolution in simulated intestinal conditions highlighted reduced precipitation of CIN when administered within PLH particles, given by a 4-5-fold improvement in the extent of CIN dissolution compared to the other delivery vehicles. Furthermore, CIN solubilization was enhanced 1.5-fold and 6-fold under simulated fasted state lipid digestion conditions when formulated with PLH particles compared to SSLH and SSLC particles, respectively. In vivo pharmacokinetics correlated well with in vitro solubilization data, whereby oral CIN bioavailability in rats, when encapsulated in the corresponding formulations, increased from SSLC < SSLH < PLH. The pharmacokinetic data obtained throughout this study indicated a synergistic effect between PLGA nanoparticles and lipid droplets in preventing CIN precipitation and thus, enhancing oral absorption. This synergy can be harnessed to efficiently deliver challenging poorly water-soluble, weak bases through oral administration.

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

In vitro and in vivo evaluation of a water-in-oil microemulsion system for enhanced peptide intestinal delivery.

PubMed

Liu, Dongyun; Kobayashi, Taku; Russo, Steven; Li, Fengling; Plevy, Scott E; Gambling, Todd M; Carson, Johnny L; Mumper, Russell J

2013-01-01

Peptide and protein drugs have become the new generation of therapeutics, yet most of them are only available as injections, and reports on oral local intestinal delivery of peptides and proteins are quite limited. The aim of this work was to develop and evaluate a water-in-oil (w/o) microemulsion system in vitro and in vivo for local intestinal delivery of water-soluble peptides after oral administration. A fluorescent labeled peptide, 5-(and-6)-carboxytetramethylrhodamine labeled HIV transactivator protein TAT (TAMRA-TAT), was used as a model peptide. Water-in-oil microemulsions consisting of Miglyol 812, Capmul MCM, Tween 80, and water were developed and characterized in terms of appearance, viscosity, conductivity, morphology, and particle size analysis. TAMRA-TAT was loaded and its enzymatic stability was assessed in modified simulated intestinal fluid (MSIF) in vitro. In in vivo studies, TAMRA-TAT intestinal distribution was evaluated using fluorescence microscopy after TAMRA-TAT microemulsion, TAMRA-TAT solution, and placebo microemulsion were orally gavaged to mice. The half-life of TAMRA-TAT in microemulsion was enhanced nearly three-fold compared to that in the water solution when challenged by MSIF. The treatment with TAMRA-TAT microemulsion after oral administration resulted in greater fluorescence intensity in all intestine sections (duodenum, jejunum, ileum, and colon) compared to TAMRA-TAT solution or placebo microemulsion. The in vitro and in vivo studies together suggested TAMRA-TAT was better protected in the w/o microemulsion in an enzyme-containing environment, suggesting that the w/o microemulsions developed in this study may serve as a potential delivery vehicle for local intestinal delivery of peptides or proteins after oral administration.

Nanoparticle-releasing nanofiber composites for enhanced in vivo vaginal retention.

PubMed

Krogstad, Emily A; Ramanathan, Renuka; Nhan, Christina; Kraft, John C; Blakney, Anna K; Cao, Shijie; Ho, Rodney J Y; Woodrow, Kim A

2017-11-01

Current approaches for topical vaginal administration of nanoparticles result in poor retention and extensive leakage. To overcome these challenges, we developed a nanoparticle-releasing nanofiber delivery platform and evaluated its ability to improve nanoparticle retention in a murine model. We individually tailored two components of this drug delivery system for optimal interaction with mucus, designing (1) mucoadhesive fibers for better retention in the vaginal tract, and (2) PEGylated nanoparticles that diffuse quickly through mucus. We hypothesized that this novel dual-functioning (mucoadhesive/mucus-penetrating) composite material would provide enhanced retention of nanoparticles in the vaginal mucosa. Equivalent doses of fluorescent nanoparticles were vaginally administered to mice in either water (aqueous suspension) or fiber composites, and fluorescent content was quantified in cervicovaginal mucus and vaginal tissue at time points from 24 h to 7d. We also fabricated composite fibers containing etravirine-loaded nanoparticles and evaluated the pharmacokinetics over 7d. We found that our composite materials provided approximately 30-fold greater retention of nanoparticles in the reproductive tract at 24 h compared to aqueous suspensions. Compared to nanoparticles in aqueous suspension, the nanoparticles in fiber composites exhibited sustained and higher etravirine concentrations after 24 h and up to 7d, demonstrating the capabilities of this new delivery platform to sustain nanoparticle release out to 3d and drug retention out to one week after a single administration. This is the first report of nanoparticle-releasing fibers for vaginal drug delivery, as well as the first study of a single delivery system that combines two components uniquely engineered for complementary interactions with mucus. Copyright © 2017 Elsevier Ltd. All rights reserved.

p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

NASA Astrophysics Data System (ADS)

Swami, Rajan; Singh, Indu; Kulhari, Hitesh; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

2015-06-01

Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere®). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

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

Stewart, J; Lindsay, P; University of Toronto, Toronto

Purpose: Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x-ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x-ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions. Methods: Two-dimensional dose kernels were measured for a 1 mmmore » circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x-ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low- and high-spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam-on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy. Results: Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery. Conclusion: The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations. Funding Support: this work is supported by funding the National Sciences and Engineering Research Council of Canada, and a Mitacs-accelerate fellowship. Conflict of Interest: Dr. Lindsay and Dr. Jaffray are listed as inventors of the small animal microirradiator described herein. This system has been licensed for commercial development.« less

SU-G-BRB-11: On the Sensitivity of An EPID-Based 3D Dose Verification System to Detect Delivery Errors in VMAT Treatments

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

Gonzalez, P; Olaciregui-Ruiz, I; Mijnheer, B

2016-06-15

Purpose: To investigate the sensitivity of an EPID-based 3D dose verification system to detect delivery errors in VMAT treatments. Methods: For this study 41 EPID-reconstructed 3D in vivo dose distributions of 15 different VMAT plans (H&N, lung, prostate and rectum) were selected. To simulate the effect of delivery errors, their TPS plans were modified by: 1) scaling of the monitor units by ±3% and ±6% and 2) systematic shifting of leaf bank positions by ±1mm, ±2mm and ±5mm. The 3D in vivo dose distributions where then compared to the unmodified and modified treatment plans. To determine the detectability of themore » various delivery errors, we made use of a receiver operator characteristic (ROC) methodology. True positive and false positive rates were calculated as a function of the γ-parameters γmean, γ1% (near-maximum γ) and the PTV dose parameter ΔD{sub 50} (i.e. D{sub 50}(EPID)-D{sub 50}(TPS)). The ROC curve is constructed by plotting the true positive rate vs. the false positive rate. The area under the ROC curve (AUC) then serves as a measure of the performance of the EPID dosimetry system in detecting a particular error; an ideal system has AUC=1. Results: The AUC ranges for the machine output errors and systematic leaf position errors were [0.64 – 0.93] and [0.48 – 0.92] respectively using γmean, [0.57 – 0.79] and [0.46 – 0.85] using γ1% and [0.61 – 0.77] and [ 0.48 – 0.62] using ΔD{sub 50}. Conclusion: For the verification of VMAT deliveries, the parameter γmean is the best discriminator for the detection of systematic leaf position errors and monitor unit scaling errors. Compared to γmean and γ1%, the parameter ΔD{sub 50} performs worse as a discriminator in all cases.« less

Nanocrystal for ocular drug delivery: hope or hype.

PubMed

Sharma, Om Prakash; Patel, Viral; Mehta, Tejal

2016-08-01

The complexity of the structure and nature of the eye emanates a challenge for drug delivery to formulation scientists. Lower bioavailability concern of conventional ocular formulation provokes the interest of researchers in the development of novel drug delivery system. Nanotechnology-based formulations have been extensively investigated and found propitious in improving bioavailability of drugs by overcoming ocular barriers prevailing in the eye. The advent of nanocrystals helped in combating the problem of poorly soluble drugs specifically for oral and parenteral drug delivery and led to development of various marketed products. Nanocrystal-based formulations explored for ocular drug delivery have been found successful in achieving increase in retention time, bioavailability, and permeability of drugs across the corneal and conjunctival epithelium. In this review, we have highlighted the ocular physiology and barriers in drug delivery. A comparative analysis of various nanotechnology-based ocular formulations is done with their pros and cons. Consideration is also given to various methods of preparation of nanocrystals with their patented technology. This article highlights the success achieved in conquering various challenges of ocular delivery by the use of nanocrystals while emphasizing on its advantages and application for ocular formulation. The perspectives of nanocrystals as an emerging flipside to explore the frontiers of ocular drug delivery are discussed.

Rumen-stable delivery systems.

PubMed

Papas; Wu

1997-12-08

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

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

PubMed Central

Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

2014-01-01

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

PubMed

Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

2014-01-01

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.

Brief report: successful pregnancies but a higher risk of preterm births in patients with systemic sclerosis: an Italian multicenter study.

PubMed

Taraborelli, Mara; Ramoni, Véronique; Brucato, Antonio; Airò, Paolo; Bajocchi, Gianluigi; Bellisai, Francesca; Biasi, Domenico; Blagojevic, Jelena; Canti, Valentina; Caporali, Roberto; Caramaschi, Paola; Chiarolanza, Ilaria; Codullo, Veronica; Cozzi, Franco; Cuomo, Giovanna; Cutolo, Maurizio; De Santis, Maria; De Vita, Salvatore; Di Poi, Emma; Doria, Andrea; Faggioli, Paola; Favaro, Maria; Ferraccioli, Gianfranco; Ferri, Clodoveo; Foti, Rosario; Gerosa, Alessandro; Gerosa, Maria; Giacuzzo, Sarah; Giani, Leopoldo; Giuggioli, Dilia; Imazio, Massimo; Iudici, Michele; Iuliano, Annamaria; Leonardi, Roberto; Limonta, Massimiliano; Lojacono, Andrea; Lubatti, Chiara; Matucci-Cerinic, Marco; Mazzone, Antonino; Meroni, Marianna; Meroni, Pier Luigi; Mosca, Marta; Motta, Mario; Muscarà, Marina; Nava, Simona; Padovan, Melissa; Pagani, Giorgio; Paolazzi, Giuseppe; Peccatori, Susanna; Ravagnani, Viviana; Riccieri, Valeria; Rosato, Edoardo; Rovere-Querini, Patrizia; Salsano, Felice; Santaniello, Alessandro; Scorza, Raffaella; Tani, Chiara; Valentini, Gabriele; Valesini, Guido; Vanoli, Massimo; Vigone, Barbara; Zeni, Silvana; Tincani, Angela

2012-06-01

To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2-193 months). SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (<34 weeks of gestation) (10% versus 5%), intrauterine growth restriction (6% versus 1%), and babies with very-low birth weight (5% versus 1%). Results of multivariable analysis showed that corticosteroid use was associated with preterm deliveries (odds ratio [OR] 3.63, 95% confidence interval [95% CI] 1.12-11.78), whereas the use of folic acid (OR 0.30, 95% CI 0.10-0.91) and presence of anti-Scl-70 antibodies (OR 0.26, 95% CI 0.08-0.85) were protective. The disease remained stable in most SSc patients, but there were 4 cases of progression of disease within 1 year from delivery, all in anti-Scl-70 antibody-positive women, 3 of whom had a disease duration of <3 years. Women with SSc can have successful pregnancies, but they have a higher-than-normal risk of preterm delivery, intrauterine growth restriction, and babies with very-low birth weight. Progression of the disease during or after pregnancy is rare, but possible. High-risk multidisciplinary management should be standard for these patients, and pregnancy should be avoided in women with severe organ damage and postponed in women with SSc of recent onset, particularly if the patient is positive for anti-Scl-70 antibodies. Copyright © 2012 by the American College of Rheumatology.

Multifunctional (3-in-1) cancer theranostics applications of hydroxyquinoline-appended polyfluorene nanoparticles† †Electronic supplementary information (ESI) available: Synthesis, characterization, stability, optical properties, imaging, drug delivery, etc. See DOI: 10.1039/c7sc03321d

PubMed Central

Chowdhury, Sayan Roy; Mukherjee, Sudip; Das, Sourav

2017-01-01

The accumulation of fluorescent hydroxyquinoline-affixed polyfluorene (PF-HQ) nanoparticles and their utility for multi-color bio-imaging and drug delivery for cancer treatment are reported. The formation of nanoparticles (PF-HQ) containing hydrophobic pockets via three-dimensional growth of a polymeric backbone in a higher water fraction (THF : H2O = 1 : 9) was observed. The nanoparticles showed incredible dual-state optical and fluorescence properties, which were further explored in multi-color cell imaging in both cancer and normal cells. The cell viability assay in various normal cells confirmed the biocompatible nature of PF-HQ, which was further supported by an ex vivo (chick chorioallantoic membrane assay) model. This encouraged us to fabricate PF-HQ-based new drug delivery systems (DDS: PF-HQ–DOX) upon conjugation with the FDA-approved anti-cancer drug doxorubicin (DOX) by filling the hydrophobic pockets of the polymer nanoparticles. The enhanced anti-cancer activity of the DDS (PF-HQ–DOX) compared with that of free DOX was observed in mouse melanoma cancer cells (B16F10) and a subcutaneous mouse (C57BL6/J) melanoma tumor model upon administration of PF-HQ–DOX. Ex vivo biodistribution studies using a fluorescence quantification method demonstrated the enhanced accumulation of DOX in tumor tissues in the PF-HQ–DOX-treated group compared to that of the free drug, signifying the drug delivery efficacy of the delivery system by a passive targeting manner. Based on the above biological data (in vitro and in the pre-clinical model), these robust and versatile fluorescent hydroxyquinoline-affixed polyfluorene (PF-HQ) nanoparticles could be effectively utilized for multifunctional biomedical applications (as they are biocompatible and can be used for bio-imaging and as a drug delivery vehicle). PMID:29568419

Comparison of double intravenous vasopressor automated system using nexfin versus manual vasopressor bolus administration for maintenance of haemodynamic stability during spinal anaesthesia for caesarean delivery: A randomised double-blind controlled trial.

PubMed

Sng, Ban Leong; Du, Wei; Lee, Man Xin; Ithnin, Farida; Mathur, Deepak; Leong, Wan Ling; Sultana, Rehena; Han, Nian-Lin R; Sia, Alex Tiong Heng

2018-05-01

Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. A randomised, double-blind controlled trial. Single-centre, KK Women's and Children's Hospital, Singapore. Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; P < 0.0001). There was no difference in the incidence of reactive hypertension or the total vasopressor requirement. The DIVA group had less wobble in system performance. Maternal and neonatal outcomes were similar. The DIVA system achieved better control of maternal blood pressure after spinal anaesthesia than manual vasopressor bolus administration. Clinicaltrials.gov identifier: NCT02277730.

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

PubMed

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

2015-01-01

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

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

NASA Astrophysics Data System (ADS)

Kaishan, Liu; Huimin, Li

2017-12-01

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

Enhanced Analgesic Responses After Preferential Delivery of Morphine and Fentanyl to the Olfactory Epithelium in Rats

PubMed Central

Hoekman, John D.; Ho, Rodney J.Y.

2011-01-01

Background Centrally acting opioid analgesics such as morphine and fentanyl are effective, but their efficacy is often limited by a delayed response or side effects resulting from systemic first-pass before reaching the brain and the central nervous system (CNS). It is generally accepted that drugs applied to the nasal cavity can directly access the brain and the CNS, which could provide therapeutic advantages such as rapid onset and lower systemic exposure. The olfactory region of the nasal cavity has been implicated in facilitating this direct nose-to-CNS transfer. If the fraction of opioid administered to the olfactory region could be improved, there could be a larger fraction of drug directly delivered to the CNS, mediating greater therapeutic benefit. Methods We have developed a pressurized olfactory delivery (POD) device to consistently and non-invasively deposit a majority of drug on the olfactory region of the nasal cavity in Sprague-Dawley rats. Using the tail-flick latency test and analysis of plasma and CNS tissue drug exposure, we compared distribution and efficacy of the opioids morphine and fentanyl administered to the nasal olfactory region with the POD device or the nasal respiratory region with nose drops or systemically via intraperitoneal (IP) injection. Results Compared to nose drop, POD administration of morphine resulted in significantly higher overall therapeutic effect (AUCeffect) without a significant increase in plasma drug exposure (AUCplasma). POD delivery of morphine resulted in a nose-to-CNS direct transport percentage of 38–55%. POD delivery of fentanyl led to a faster (5 min vs. 10 min) and more intense analgesic effect compared to nasal respiratory administration. Unlike IP injection or nose drop administration, both morphine and fentanyl given by the POD device to olfactory nasal epithelium exhibited clockwise [plasma] versus effect hysteresis after nasal POD administration, consistent with direct nose-to-CNS drug transport mechanism. Conclusions Deposition of opioids to the olfactory region within the nasal cavity could have a significant impact on drug distribution and pharmacodynamic effect, and thus should be considered into account in future nasally administered opioid studies. PMID:21709146

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

Wu, J; Hill, G; Spiegel, J

Purpose: To investigate the clinical and dosimetric benefits of automatic gating of left breast mixed with breath-hold technique. Methods: Two Active Breathing Control systems, ABC2.0 and ABC3.0, were used during simulation and treatment delivery. The two systems are different such that ABC2.0 is a breath-hold system without beam control capability, while ABC3.0 has capability in both breath-hold and beam gating. At simulation, each patient was scanned twice: one with free breathing (FB) and one with breath hold through ABC. Treatment plan was generated on the CT with ABC. The same plan was also recalculated on the CT with FB. Thesemore » two plans were compared to assess plan quality. For treatments with ABC2.0, beams with MU > 55 were manually split into multiple subfields. All subfields were identical and shared the total MU. For treatment with ABC3.0, beam splitting was unnecessary. Instead, treatment was delivered in gating mode mixed with breath-hold technique. Treatment delivery efficiency using the two systems was compared. Results: The prescribed dose was 50.4Gy at 1.8Gy/fraction. The maximum heart dose averaged over 10 patients was 46.0±2.5Gy and 24.5±12.2Gy for treatments with FB and with ABC respectively. The corresponding heart V10 was 13.2±3.6% and 1.0±1.6% respectively. The averaged MUs were 99.8±7.5 for LMT, 99.2±9.4 for LLT. For treatment with ABC2.0, normally the original beam was split into 2 subfields. The averaged total time to delivery all beams was 4.3±0.4min for treatments with ABC2.0 and 3.3±0.6min for treatments with ABC3.0 in gating mode. Conclusion: Treatment with ABC tremendously reduced heart dose. Compared to treatments with ABC2.0, gating with ABC3.0 reduced the total treatment time by 23%. Use of ABC3.0 improved the delivery efficiency, and eliminated the possibility of mistreatments. The latter may happen with ABC2.0 where beam is not terminated when breath signal falls outside of the treatment window.« less

Leveraging the trusted clinician: increasing retention in disease management through integrated program delivery.

PubMed

Frazee, Sharon Glave; Sherman, Bruce; Fabius, Raymond; Ryan, Pamela; Kirkpatrick, Patricia; Davis, Jeffery

2008-10-01

Disease management's (DM's) value largely depends on achieving and maintaining participation. Simply being enrolled in a program does not guarantee engaged participation by enrollees, a necessary factor to achieve the improved health outcomes and subsequent reduced health care costs that are the ultimate objective of DM. The objective of this study is to test the hypothesis that an integrated disease management (IDM) protocol (patent-pending), which combines telephonic-delivered disease management (TDM) with a worksite-based primary care center and pharmacy delivery, yields higher patient retention rates than traditional remote DM alone. An earlier study of the IDM protocol found that integrating a worksite-based primary care and pharmacy delivery system with traditional telephonic-based DM substantially increased contact, enrollment, and engagement rates compared to traditional stand-alone telephonic DM. This prospective cohort study tracks contact and enrollment rates for persons assigned to either IDM or traditional TDM protocols and compares participation rates at 6- and 12-month intervals as well as measures of continued retention in the DM program. The IDM protocol showed a significant improvement in participation persistence over traditional TDM. Integrating a worksite-based primary care and pharmacy delivery system led by "trusted clinicians at the workplace"trade mark with traditional telephonic-based DM not only increases contact and enrollment rates, but also results in higher patient engagement and retention. These improvements in participation are expected to result in improved outcomes for a larger proportion of the target population than traditional telephonic DM.

Comparing mandated health care reforms: the Affordable Care Act, accountable care organizations, and the Medicare ESRD program.

PubMed

Watnick, Suzanne; Weiner, Daniel E; Shaffer, Rachel; Inrig, Jula; Moe, Sharon; Mehrotra, Rajnish

2012-09-01

In addition to extending health insurance coverage, the Affordable Care Act of 2010 aims to improve quality of care and contain costs. To this end, the act allowed introduction of bundled payments for a range of services, proposed the creation of accountable care organizations (ACOs), and established the Centers for Medicare and Medicaid Innovation to test new care delivery and payment models. The ACO program began April 1, 2012, along with demonstration projects for bundled payments for episodes of care in Medicaid. Yet even before many components of the Affordable Care Act are fully in place, the Medicare ESRD Program has instituted legislatively mandated changes for dialysis services that resemble many of these care delivery reform proposals. The ESRD program now operates under a fully bundled, case-mix adjusted prospective payment system and has implemented Medicare's first-ever mandatory pay-for-performance program: the ESRD Quality Incentive Program. As ACOs are developed, they may benefit from the nephrology community's experience with these relatively novel models of health care payment and delivery reform. Nephrologists are in a position to assure that the ACO development will benefit from the ESRD experience. This article reviews the new ESRD payment system and the Quality Incentive Program, comparing and contrasting them with ACOs. Better understanding of similarities and differences between the ESRD program and the ACO program will allow the nephrology community to have a more influential voice in shaping the future of health care delivery in the United States.

Topical Non-Iontophoretic Application of Acetylcholine and Nitroglycerin via a Translucent Patch: A New Means for Assessing Microvascular Reactivity

PubMed Central

Schonberger, Robert B.; Worden, William S.; Shahmohammadi, Kaveh; Menn, Kirsten; Silverman, Tyler J.; Stout, Robert G.; Shelley, Kirk H.; Silverman, David G.

2007-01-01

Objective: Assessments of endothelial cell function with acetylcholine have typically used systemic, regional intra-arterial, or iontophoretic delivery of drug. Each of these techniques induces systemic and/or local changes that compromise their safety or effectiveness. Using translucent drug preparations applied under laser Doppler flowmetry (LDF) probes, we tested whether local vasodilation can be induced with non-iontophoretic transdermal delivery of acetylcholine and how such dilation would compare to the dilation achieved with topical nitroglycerin in healthy volunteers. Methods: Ten subjects without known vascular disease were recruited for LDF monitoring at sites of drug application for this preliminary investigation. Topical acetylcholine chloride, nitroglycerin, and placebo were applied via translucent patches to the forehead directly below LDF probes. Results: LDF readings increased by 406 percent (245 percent to 566 percent) and 36 percent (26 percent to 46 percent), respectively, at the acetylcholine and placebo sites (p = .005 by Wilcoxon Signed Rank Test (WSRT) for acetylcholine vs. placebo); and they increased by 365 percent (179 percent to 550 percent) at the nitroglycerin site (p = .005 by WSRT for nitroglycerin vs. placebo; p = .6 vs. acetylcholine). Conclusion: Transdermal delivery of acetylcholine can induce significant local vasodilatory responses comparable to those achieved with nitroglycerin without requiring iontophoresis. The means of transdermal delivery and monitoring described herein may constitute a new minimally invasive way to interrogate the microvasculature and thereby assess the microcirculatory changes induced by various disorders and therapeutic interventions. PMID:17876370

Quantifying Northern Goshawk diets using remote cameras and observations from blinds

USGS Publications Warehouse

Rogers, A.S.; DeStefano, S.; Ingraldi, M.F.

2005-01-01

Raptor diet is most commonly measured indirectly, by analyzing castings and prey remains, or directly, by observing prey deliveries from blinds. Indirect methods are not only time consuming, but there is evidence to suggest these methods may overestimate certain prey taxa within raptor diet. Remote video surveillance systems have been developed to aid in monitoring and data collection, but their use in field situations can be challenging and is often untested. To investigate diet and prey delivery rates of Northern Goshawks (Accipiter gentilis), we operated 10 remote camera systems at occupied nests during the breeding seasons of 1999 and 2000 in east-central Arizona. We collected 2458 hr of useable video and successfully identified 627 (93%) prey items at least to Class (Aves, Mammalia, or Reptilia). Of prey items identified to genus, we identified 344 (81%) mammals, 62 (15%) birds, and 16 (4%) reptiles. During camera operation, we also conducted observations from blinds at a subset of five nests to compare the relative efficiency and precision of both methods. Limited observations from blinds yielded fewer prey deliveries, and therefore, lower delivery rates (0.16 items/hr) than simultaneous video footage (0.28 items/hr). Observations from blinds resulted in fewer prey identified to the genus and species levels, when compared to data collected by remote cameras. Cameras provided a detailed and close view of nests, allowed for simultaneous recording at multiple nests, decreased observer bias and fatigue, and provided a permanent archive of data. ?? 2005 The Raptor Research Foundation, Inc.

Nanoparticle bioconjugate for controlled cellular delivery of doxorubicin

NASA Astrophysics Data System (ADS)

Sangtani, Ajmeeta; Petryayeva, Eleonora; Wu, Miao; Susumu, Kimihiro; Oh, Eunkeu; Huston, Alan L.; Lasarte-Aragones, Guillermo; Medintz, Igor L.; Algar, W. Russ; Delehanty, James B.

2018-02-01

Nanoparticle (NP)-mediated drug delivery offers the potential to overcome limitations of systemic delivery, including the ability to specifically target cargo and control release of NP-associated drug cargo. Doxorubicin (DOX) is a widely used FDA-approved cancer therapeutic; however, multiple side effects limit its utility. Thus, there is wide interest in modulating toxicity after cell delivery. Our goal here was to realize a NP-based DOX-delivery system that can modulate drug toxicity by controlling the release kinetics of DOX from the surface of a hard NP carrier. To achieve this, we employed a quantum dot (QD) as a central scaffold which DOX was appended via three different peptidyl linkages (ester, disulfide, hydrazone) that are cleavable in response to various intracellular conditions. Attachment of a cell penetrating peptide (CPP) containing a positively charged polyarginine sequence facilitates endocytosis of the ensemble. Polyhistidine-driven metal affinity coordination was used to self-assemble both peptides to the QD surface, allowing for fine control over both the ratio of peptides attached to the QD as well as DOX dose delivered to cells. Microplate-based Förster resonance energy transfer assays confirmed the successful ratiometric assembly of the conjugates and functionality of the linkages. Cell delivery experiments and cytotoxicity assays were performed to compare the various cleavable linkages to a control peptide where DOX is attached through an amide bond. The role played by various attachment chemistries used in QD-peptide-drug assemblies and their implications for the rationale in design of NPbased constructs for drug delivery is described here.

Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo.

PubMed

Obata, Yosuke; Tajima, Shoji; Takeoka, Shinji

2010-03-03

We developed pH-responsive liposomes containing synthetic glutamic acid-based zwitterionic lipids and evaluated their properties both in vitro and in vivo with the aim of constructing an efficient liposome-based systemic drug delivery system. The glutamic acid-based lipids; 1,5-dihexadecyl N-glutamyl-L-glutamate (L1) and 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (L2) were synthesized as a pH-responsive component of liposomes that respond to endosomal pH. The zeta potential of liposomes containing L1 or L2 was positive when the solution pH was below 4.6 or 5.6, respectively, but negative at higher pH values. The pH-responsive liposomes showed improved fusogenic potential to an endosome-mimicking anionic membrane at acidic pH, where the zeta potential of the liposomes was positive. We then prepared doxorubicin (DOX)-encapsulating liposomes containing L1 or L2, and clarified by confocal microscopic studies that the contents were rapidly transferred into both the cytoplasm and nucleus. Release of DOX from the endosomes mediated by the pH-responsive liposomes dramatically inhibited cancer cell growth. The L2-liposomes were slightly more effective than L1-liposomes as a drug delivery system. Intravenously injected L2-liposomes displayed blood persistence comparable to that of conventional phospholipid (PC)-based liposomes. Indeed, the antitumor efficacy of L2-liposomes was higher than that of PC-based liposomes against a xenograft breast cancer tumor in vivo. Thus, the high performance of L2-liposomes results from both efficient intracellular drug delivery and comparable blood persistence in comparison with the conventional PC-based liposomes in vitro and in vivo. Copyright 2009 Elsevier B.V. All rights reserved.

Approaches to Neural Tissue Engineering Using Scaffolds for Drug Delivery

PubMed Central

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

2007-01-01

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

Modeling the Delivery Physiology of Distributed Learning Systems.

ERIC Educational Resources Information Center

Paquette, Gilbert; Rosca, Ioan

2003-01-01

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

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

Liu, R; Liu, T; Qi, S

Purposes: There has been growing interest in treating breast cancer using VMAT technique. Our goal is to compare the dosimetry and treatment delivery parameters for the left-sided breast cancer treatment using various VMAT platforms from commercially available planning systems. Methods: Five consecutive left-sided breast cancer patients initially treated with conventional 3D-conformal radiotherapy (3DCRT) were selected. Four VMAT plans using most popular treatment planning systems, including Eclipse (Version 11, Varian), Pinnacle (Version 9.8, Philips), Monaco (Version 2.03, Elekta) and helical Tomotherapy (V4.0, Accuray). The same structure set and same planning goals were used for all VMAT plans. The dosimetric parameters includingmore » target coverage and minimum/maximum/mean, dose-volume endpoints for the selected normal structures: the heart, ipsilateral-/contralateral lung and breast, were evaluated. Other dosimetric indices including heterogeneity index (HI) were evaluated. The treatment delivery parameters, such as monitor unit (MUs) and delivery time were also compared. Results: VMAT increases dose homogeneity to the treated volume and reduces the irradiated heart and left-lung volumes. Compared to the 3DCRT technique, all VMAT plans offer better heart and left-lung dose sparing; the mean heart doses were 4.5±1.6(Monaco), 1.2±0.4(Pinnacle), 1.3± (Eclipse) and 5.6±4.4(Tomo), the mean left-lung doses were 5.9±1.5(Monaco), 3.7±0.7(Pinnacle), 1.4± (Eclipse) and 5.2±1.6 (Tomo), while for the 3DCRT plan, the mean heart and left-Lung doses were 2.9±2.0, and 6.8±4.4 (Gy) respectively. The averaged contralateral-breast and lung mean doses were higher in VMAT plans than the 3DCRT plans but were not statistically significant. Among all the VMAT plans, the Pinnacle plans often yield the lowest right-lung/breast mean doses, and slightly better heterogeneity indices that are similar to Tomotherapy plans. Treatment delivery time of the VMAT plans (except helical Tomotherapy IMRT) is estimated to be comparable with the conventional 3DCRT. Conclusion: VMAT achieves equal or better PTV coverage and comparable OARs sparing compared to the conventional 3DCRT techniques.« less

Comparative analysis of the vapor headspace of military-grade TNT versus NESTT TNT under dynamic and static conditions

NASA Astrophysics Data System (ADS)

Edge, Cindy C.; Gibb, Julie; Wasserzug, Louis S.

1998-09-01

The Institute for Biological Detection Systems (IBDS) has developed a quantitative vapor delivery system that can aid in characterizing dog's sensitivity and ability to recognize odor signatures for explosives and contraband substances. Determining of the dog's odor signature for detection of explosives is important because it may aid in eliminating the risk of handling explosives and reducing cross-contamination. Progress is being made in the development of training aids that represent the headspace of the explosives. NESTTTM TNT materials have been proposed as an approach to developing training aid simulates. In order for such aids to be effective they must mimic the headspace of the target material. This study evaluates the NESTTTM TNT product with regard to this criterion. NESTTTM TNT vapor was generated by the IBDS vapor delivery system, which incorporates a vapor generation cell that enables the user to control the conditions under which a substance is tested. The NESTTTM TNT vapor was compared to the headspace of military-grade TNT. The findings identify and quantify major vapor constituents of military-grade TNT and NESTTTM TNT. A comparative analysis evaluated the degree to which the NESTTTM TNT mimics the headspace of an actual TNT sample.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

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

2012-01-01

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

Micro injector sample delivery system for charged molecules

DOEpatents

Davidson, James C.; Balch, Joseph W.

1999-11-09

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

Prototype system of secure VOD

NASA Astrophysics Data System (ADS)

Minemura, Harumi; Yamaguchi, Tomohisa

1997-12-01

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

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

PubMed

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

2011-05-01

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

Secondary nuclear targeting of mesoporous silica nano-particles for cancer-specific drug delivery based on charge inversion

PubMed Central

Wang, Xiyong; Fan, Xiaobo; Wu, Guoqiu

2016-01-01

A novel multifunctional nano-drug delivery system based on reversal of peptide charge was successfully developed for anticancer drug delivery and imaging. Mesoporous silica nano-particles (MSN) ~50 nm in diameter were chosen as the drug reservoirs, and their surfaces were modified with HIV-1 transactivator peptide-fluorescein isothiocyanate (TAT-FITC) and YSA-BHQ1. The short TAT peptide labeled with FITC was used to facilitate intranuclear delivery, while the YSA peptide tagged with the BHQ1 quencher group was used to specifically bind to the tumor EphA2 membrane receptor. Citraconic anhydride (Cit) was used to invert the charge of the TAT peptide in neutral or weak alkaline conditions so that the positively charged YSA peptide could combine with the TAT peptide through electrostatic attraction. The FITC fluorescence was quenched by the spatial approach of BHQ1 after the two peptides bound to each other. However, the Cit-amino bond was unstable in the acidic atmosphere, so the positive charge of the TAT peptide was restored and the positively charged YSA moiety was repelled. The FITC fluorescence was recovered after the YSA-BHQ1 moiety was removed, and the TAT peptide led the nano-particles into the nucleolus. This nano-drug delivery system was stable at physiological pH, rapidly released the drug in acidic buffer, and was easily taken up by MCF-7 cells. Compared with free doxorubicin hydrochloride at an equal concentration, this modified MSN loaded with doxorubicin molecules had an equivalent inhibitory effect on MCF-7 cells. This nano-drug delivery system is thus a promising method for simultaneous cancer diagnosis and therapy. PMID:27661121

Secondary nuclear targeting of mesoporous silica nano-particles for cancer-specific drug delivery based on charge inversion.

PubMed

Zhao, Jianwen; Zhao, Fengfeng; Wang, Xiyong; Fan, Xiaobo; Wu, Guoqiu

2016-10-25

A novel multifunctional nano-drug delivery system based on reversal of peptide charge was successfully developed for anticancer drug delivery and imaging. Mesoporous silica nano-particles (MSN) ~50 nm in diameter were chosen as the drug reservoirs, and their surfaces were modified with HIV-1 transactivator peptide-fluorescein isothiocyanate (TAT-FITC) and YSA-BHQ1. The short TAT peptide labeled with FITC was used to facilitate intranuclear delivery, while the YSA peptide tagged with the BHQ1 quencher group was used to specifically bind to the tumor EphA2 membrane receptor. Citraconic anhydride (Cit) was used to invert the charge of the TAT peptide in neutral or weak alkaline conditions so that the positively charged YSA peptide could combine with the TAT peptide through electrostatic attraction. The FITC fluorescence was quenched by the spatial approach of BHQ1 after the two peptides bound to each other. However, the Cit-amino bond was unstable in the acidic atmosphere, so the positive charge of the TAT peptide was restored and the positively charged YSA moiety was repelled. The FITC fluorescence was recovered after the YSA-BHQ1 moiety was removed, and the TAT peptide led the nano-particles into the nucleolus. This nano-drug delivery system was stable at physiological pH, rapidly released the drug in acidic buffer, and was easily taken up by MCF-7 cells. Compared with free doxorubicin hydrochloride at an equal concentration, this modified MSN loaded with doxorubicin molecules had an equivalent inhibitory effect on MCF-7 cells. This nano-drug delivery system is thus a promising method for simultaneous cancer diagnosis and therapy.

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

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

Chang, X; Yang, D

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

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

Code of Federal Regulations, 2011 CFR

2011-10-01

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

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2013 CFR

2013-10-01

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

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

Code of Federal Regulations, 2014 CFR

2014-10-01

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

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

Code of Federal Regulations, 2012 CFR

2012-10-01

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

Effect of severity of illness on cesarean delivery rates in Washington State.

PubMed

Hitti, Jane; Walker, Suzan; Benedetti, Thomas J

2017-10-01

Hospitals and providers are increasingly held accountable for their cesarean delivery rates. In the perinatal quality improvement arena, there is vigorous debate about whether all hospitals can be held to the same benchmark for an acceptable cesarean rate regardless of patient acuity. However, the causes of variation in hospital cesarean delivery rates are not well understood. We sought to evaluate the association and temporal trends between severity of illness at admission and the primary term singleton vertex cesarean delivery rate among hospitals in Washington State. We hypothesized that hospitals with higher patient acuity would have higher cesarean delivery rates and that this pattern would persist over time. In this cross-sectional analysis, we analyzed aggregate hospital-level data for all nonmilitary hospitals in Washington State with ≥100 deliveries/y during federal fiscal years 2010 through 2014 (287,031 deliveries). Data were obtained from the Washington State Comprehensive Hospital Abstract Reporting System, which includes inpatient demographic, diagnosis, procedure, and discharge information derived from hospital billing systems. Age, admission diagnoses and procedure codes were converted to patient-level admission severity-of-illness scores using the All Patient Refined Diagnosis Related Groups classification system. This system is widely used throughout the United States to adjust hospital data for severity of illness. Mean admission hospital-level severity-of-illness scores were calculated for each fiscal year among the term singleton vertex population with no history of cesarean delivery. We used linear regression to evaluate the association between hospital admission severity of illness and the primary term singleton vertex cesarean delivery rate, calculated Pearson correlation coefficients, and compared regression line slopes and 95% confidence intervals for each fiscal year. Hospitals were diverse with respect to delivery volume, level of care, and geographic location within Washington. Hospital aggregate admission severity-of-illness score correlated with primary term singleton vertex cesarean delivery rate in all fiscal years (R 2 0.38-0.58, P < .001). For every year in the study interval, as admission severity of illness increased so did the primary term singleton vertex cesarean rate. The slope of the regression line decreased during the study interval, suggesting that statewide decrease in primary term singleton vertex cesarean rate occurred across the range of severity of illness. Admission severity-of-illness score is strongly associated with the primary term singleton vertex cesarean delivery rate among hospitals in Washington State. Approximately 50% of variation in hospital primary term singleton vertex cesarean delivery rates appeared to be related to admission severity of illness. This relationship persisted over time despite a statewide decrease in cesarean delivery, suggesting that patient acuity will likely continue to contribute to hospital variation in cesarean delivery rates despite perinatal quality improvement efforts. The major implication of this study is that patient acuity should be considered when determining optimal cesarean delivery rates. High-acuity hospitals are likely to have high cesarean rates because they provide a specific role in serving regional needs. To hold these centers to an arbitrary benchmark may jeopardize the funding necessary to support regional safety net institutions. Copyright © 2017. Published by Elsevier Inc.

Estimating the Hospital Delivery Costs Associated With Severe Maternal Morbidity in New York City, 2008-2012.

PubMed

Howland, Renata E; Angley, Meghan; Won, Sang Hee; Wilcox, Wendy; Searing, Hannah; Tsao, Tsu-Yu

2018-02-01

To quantify the average and total hospital delivery costs associated with severe maternal morbidity in excess of nonsevere maternal morbidity deliveries over a 5-year period in New York City adjusting for other sociodemographic and clinical factors. We conducted a population-based cross-sectional study using linked birth certificates and hospital discharge data for New York City deliveries from 2008 to 2012. Severe maternal morbidity was defined using a published algorithm of International Classification of Diseases, 9 Revision, Clinical Modification disease and procedure codes. Hospital costs were estimated by converting hospital charges using factors specific to each year and hospital and to each diagnosis. These estimates approximate what it costs the hospital to provide services (excluding professional fees) and were used in all subsequent analyses. To estimate adjusted mean costs associated with severe maternal morbidity, we used multivariable regression models with a log link, gamma distribution, robust standard errors, and hospital fixed effects, controlling for age, race and ethnicity, neighborhood poverty, primary payer, number of deliveries, method of delivery, comorbidities, and year. We used the adjusted mean cost to determine the average and total hospital delivery costs associated with severe maternal morbidity in excess of nonsevere maternal morbidity deliveries from 2008 to 2012. Approximately 2.3% (n=13,502) of all New York City delivery hospitalizations were complicated by severe maternal morbidity. Compared with nonsevere maternal morbidity deliveries, these hospitalizations were clinically complicated, required more and intensive clinical services, and had a longer stay in the hospital. The average cost of delivery with severe maternal morbidity was $14,442 (95% CI $14,128-14,756), compared with $7,289 (95% CI $7,276-7,302) among deliveries without severe maternal morbidity. After adjusting for other factors, the difference between deliveries with and without severe maternal morbidity remained high ($6,126). Over 5 years, this difference resulted in approximately $83 million in total excess costs (13,502×$6,126). Severe maternal morbidity nearly doubled the cost of delivery above and beyond other drivers of cost, resulting in tens of millions of excess dollars spent in the health care system in New York City. These findings can be used to demonstrate the burden of severe maternal morbidity and evaluate the cost-effectiveness of interventions to improve maternal health.

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

PubMed

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

2018-02-01

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

A Native American Community with a 7% Cesarean Delivery Rate: Does Case Mix, Ethnicity, or Labor Management Explain the Low Rate?

PubMed Central

Leeman, Lawrence; Leeman, Rebecca

2003-01-01

PURPOSE Cesarean delivery rates vary widely across populations. Studying communities with low rates of cesarean delivery may identify practices that can lower the cesarean rate. METHODS A population-based historical cohort study included all pregnant women (N = 1132) from 1992 through 1996 in a predominantly Native American region of northwestern New Mexico known to have a high prevalence of gestational diabetes and preeclampsia. The outcomes studied included delivery type (eg, cesarean, operative vaginal, spontaneous vaginal), indication for cesarean delivery, presence of obstetrical risk factors, and use of labor induction or augmentation. RESULTS The cesarean delivery rate of the study group (7.3%) was only 35% of the 1996 US rate of 20.7%. Among study participants, the relative risk of a primary cesarean delivery for dystocia was 0.22 (95% CI, 0.14, 0.35). Trial of labor after cesarean delivery was attempted by 93% of study participants compared with 42% of women nationwide in 1994. The cesarean delivery rates for women with diabetes in pregnancy (11.5% versus 35.4%) and preeclampsia (14.8% versus 37.4%) were significantly lower than nationwide rates. Case-mix analysis comparison with a standardized population and comparison of standard (ie, term, singleton, vertex) primiparous women demonstrate that the low rate of cesarean delivery was not because of a lower prevalence of risk factors. CONCLUSIONS The community’s low rate of cesarean delivery is primarily the result of a decreased use of cesarean delivery for labor dystocia and an almost universal acceptance of trial of labor after cesarean delivery. Cultural attitudes toward childbirth, design of the perinatal system, and genetic factors also may explain the low rate of cesarean delivery. PMID:15043178

A Native American community with a 7% cesarean delivery rate: does case mix, ethnicity, or labor management explain the low rate?

PubMed

Leeman, Lawrence; Leeman, Rebecca

2003-01-01

Cesarean delivery rates vary widely across populations. Studying communities with low rates of cesarean delivery may identify practices that can lower the cesarean rate. A population-based historical cohort study included all pregnant women (N = 1132) from 1992 through 1996 in a predominantly Native American region of northwestern New Mexico known to have a high prevalence of gestational diabetes and preeclampsia. The outcomes studied included delivery type (eg, cesarean, operative vaginal, spontaneous vaginal), indication for cesarean delivery, presence of obstetrical risk factors, and use of labor induction or augmentation. The cesarean delivery rate of the study group (7.3%) was only 35% of the 1996 US rate of 20.7%. Among study participants, the relative risk of a primary cesarean delivery for dystocia was 0.22 (95% CI, 0.14, 0.35). Trial of labor after cesarean delivery was attempted by 93% of study participants compared with 42% of women nationwide in 1994. The cesarean delivery rates for women with diabetes in pregnancy (11.5% versus 35.4%) and preeclampsia (14.8% versus 37.4%) were significantly lower than nationwide rates. Case-mix analysis comparison with a standardized population and comparison of standard (ie, term, singleton, vertex) primiparous women demonstrate that the low rate of cesarean delivery was not because of a lower prevalence of risk factors. The community's low rate of cesarean delivery is primarily the result of a decreased use of cesarean delivery for labor dystocia and an almost universal acceptance of trial of labor after cesarean delivery. Cultural attitudes toward childbirth, design of the perinatal system, and genetic factors also may explain the low rate of cesarean delivery.

Integrated model for pricing, delivery time setting, and scheduling in make-to-order environments

NASA Astrophysics Data System (ADS)

Garmdare, Hamid Sattari; Lotfi, M. M.; Honarvar, Mahboobeh

2018-03-01

Usually, in make-to-order environments which work only in response to the customer's orders, manufacturers for maximizing the profits should offer the best price and delivery time for an order considering the existing capacity and the customer's sensitivity to both the factors. In this paper, an integrated approach for pricing, delivery time setting and scheduling of new arrival orders are proposed based on the existing capacity and accepted orders in system. In the problem, the acquired market demands dependent on the price and delivery time of both the manufacturer and its competitors. A mixed-integer non-linear programming model is presented for the problem. After converting to a pure non-linear model, it is validated through a case study. The efficiency of proposed model is confirmed by comparing it to both the literature and the current practice. Finally, sensitivity analysis for the key parameters is carried out.

Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle

NASA Astrophysics Data System (ADS)

Chen, Yao; Xu, Mengjiao; Guo, Yi; Tu, Keyao; Wu, Weimin; Wang, Jianjun; Tong, Xiaowen; Wu, Wenjuan; Qi, Lifeng; Shi, Donglu

2017-01-01

Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe3O4 NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.

Nanoparticles Engineered from Lecithin-in-Water Emulsions As A Potential Delivery System for Docetaxel

PubMed Central

Yanasarn, Nijaporn; Sloat, Brian R.; Cui, Zhengrong

2009-01-01

Docetaxel is a potent anti-cancer drug. However, there continues to be a need for alternative docetaxel delivery systems to improve its efficacy. We reported the engineering of a novel spherical nanoparticle formulation (~270 nm) from lecithin-in-water emulsions. Docetaxel can be incorporated into the nanoparticles, and the resultant docetaxel-nanoparticles were stable when stored as an aqueous suspension. The release of the docetaxel from the nanoparticles was likely caused by a combination of diffusion and Case II transport. The docetaxel-in-nanoparticles were more effective in killing tumor cells in culture than free docetaxel. Moreover, the docetaxel-nanoparticles did not cause any significant red blood cell lysis or platelet aggregation in vitro, nor did they induce detectable acute liver damage when injected intravenously into mice. Finally, compared to free docetaxel, the intravenously injected docetaxel-nanoparticles increased the accumulation of the docetaxel in a model tumor in mice by 4.5-fold. These lecithin-based nanoparticles have the potential to be a novel biocompatible and efficacious delivery system for docetaxel. PMID:19524029

Doxorubicin-loaded platelets conjugated with anti-CD22 mAbs: a novel targeted delivery system for lymphoma treatment with cardiopulmonary avoidance

PubMed Central

Zhou, Rongfu; Wang, Fan; Liu, Xu; Ouyang, Jian; Chen, Bing

2017-01-01

B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX–platelet–CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs. Anti-CD22 mAb-labeled platelets can precisely deliver DOX to tumor cells. Our in vitro and in vivo experiments showed the enhanced antitumor activity and attenuated cardiotoxicity of DOX when delivered as DOX–platelet–CD22. Compared with other delivery systems, the uptake of DOX–platelet–CD22 by macrophage-like cells decreased. Moreover, DOX–platelet–CD22 showed platelet properties, such as tumor cell-induced platelet aggregation. Therefore, targeted chemotherapy that is mediated by DOX–platelet–CD22 is a promising option for lymphoma treatment. PMID:28938559

Doxorubicin-loaded platelets conjugated with anti-CD22 mAbs: a novel targeted delivery system for lymphoma treatment with cardiopulmonary avoidance.

PubMed

Xu, Peipei; Zuo, Huaqin; Zhou, Rongfu; Wang, Fan; Liu, Xu; Ouyang, Jian; Chen, Bing

2017-08-29

B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs. Anti-CD22 mAb-labeled platelets can precisely deliver DOX to tumor cells. Our in vitro and in vivo experiments showed the enhanced antitumor activity and attenuated cardiotoxicity of DOX when delivered as DOX-platelet-CD22. Compared with other delivery systems, the uptake of DOX-platelet-CD22 by macrophage-like cells decreased. Moreover, DOX-platelet-CD22 showed platelet properties, such as tumor cell-induced platelet aggregation. Therefore, targeted chemotherapy that is mediated by DOX-platelet-CD22 is a promising option for lymphoma treatment.

A nano-delivery system for bioactive ingredients using supercritical carbon dioxide and its release behaviors.

PubMed

Situ, Wenbei; Song, Xianliang; Luo, Shucan; Liang, Yan

2017-08-01

For the purpose of ensuring the bioavailability of bioactive ingredients, a nano-delivery system with low toxicity was developed using supercritical carbon dioxide (SC-CO 2 ). Compared to thin-film hydration (TFH), obtaining nano-scale liposomes is easier using SC-CO 2 . The characteristic of these liposomes was also demonstrated by the analysis of particle size and morphology. An in vitro release study showed that liposomes produced using SC-CO 2 were resistant to low pH in simulated gastric conditions. In a simulated intestinal environment, enteric solubility of these liposomes was enhanced, which are important properties for controlled releasing bioactive ingredient. Furthermore, SC-CO 2 -produced liposomes had a higher storage stability than those produced using TFH. Analysis of the organic solvent residue in the liposomes by gas chromatography-mass spectrometry (GC-MS) indicated that SC-CO 2 -produced liposomes had lower toxicity than those produced by TFH. A chemical free nano-delivery system using SC-CO 2 has been revealed for storage and controlled release of bioactive ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Caesarean section rate and cost control effectiveness of case payment reform in the new cooperative medical scheme for delivery: evidence from Xi County, China.

PubMed

Liu, Shuang; Wang, Jing; Zhang, Liang; Zhang, Xiang

2018-03-09

In China, increases in both the caesarean section (CS) rates and delivery costs have raised questions regarding the reform of the medical insurance payment system. Case payment is useful for regulating the behaviour of health providers and for controlling the CS rates and excessive increases in medical expenses. New Cooperative Medical Scheme (NCMS) agencies in Xi County in Henan Province piloted a case payment reform (CPR) in delivery for inpatients. We aimed to observe the changes in the CS rates, compare the changes in delivery-related variables, and identify variables related to delivery costs before and after the CPR in Xi County. Overall, 28,314 cases were selected from the Xi County NCMS agency from 2009 to 2010 and from 2014 to 2015. One-way ANOVA and chi-square tests were used to compare the distributions of CS and vaginal delivery (VD) before and after the CPR under different indicators. We applied multivariate linear regressions for the total medical cost of the VD and CS groups and total samples to identify the relationships between medical expenses and variables. The CS rates in Xi County increased from 26.1% to 32.5% after the CPR. The length of stay (LOS), total medical cost, and proportion of county hospitals increased in the CS and VD groups after the CPR, which had significant differences. The total medical cost in the CS and VD groups as well as the total samples was significantly influenced by inpatient age, LOS, and hospital type, and had a significant correlation with the CPR in the VD group and the total samples. The CPR might fail to control the growth of unreasonable medical expenses and regulate the behaviour of providers, which possibly resulted from the unreasonable compensation standard of case payments, prolonged LOS, and the increasing proportion of county hospitals. The NCMS should modify the case payment standard of delivery to inhibit providers' motivation to render CS services. The LOS should be controlled by implementing clinical guidelines, and a reference system should be established to guide patients in choosing reasonable hospitals.

Role of Tranexamic Acid in Reducing Blood Loss in Vaginal Delivery.

PubMed

Roy, Priyankur; Sujatha, M S; Bhandiwad, Ambarisha; Biswas, Bivas

2016-10-01

Anti-fibrinolytic agents are used to reduce obstetric blood loss as the fibrinolytic system is known to get activated after placental delivery. To evaluate the efficacy of parenteral tranexamic acid in reducing blood loss during normal labour and to compare it with the amount of blood loss in patients who received placebo in the third stage of labour. Patients with spontaneous labour or planned for induction of labour and fulfilling the inclusion criteria were recruited for the study. In each patient, the pre-delivery pulse rate, blood pressure, Hb gm% and PCV% were noted. Labour was monitored carefully using a partogram. The study group received Inj. Oxytocin and Inj. Tranexamic acid. The control group received Inj. Oxytocin and Placebo injection. Immediately after delivery of the baby, when all the liquor was drained, the patient was placed over a blood drape-a disposable conical, graduated plastic collection bag. The amount of blood collected in the blood drape was measured. Then the patient was given pre-weighed pads, which were weighed 2 h post-partum. The blood loss was measured by measuring the blood collected in the drape and by weighing the swabs before and after delivery. The total number of patients studied was 100-equally distributed in both the groups. The age group of the patients and BMI were comparable. There was a significant increase in the pulse rate and decrease in blood pressure in the control group as compared with the study group. The post-delivery haemoglobin and haematocrit were significantly reduced in the control group as compared to the study group. The mean blood loss at the end of 2 h was 105 ml in the study group and 252 ml in the control group. There was a significant increase in the usage of uterotonics and also in the need for blood transfusion in the control group; 12 % of the patients in the control group had to stay for more than 3 days compared to 2 % in the study group. Tranexamic acid injection, an antifibrinolytic agent when given prophylactically after the delivery of the baby, by intravenous route appears to reduce the blood loss and maternal morbidity during normal labour effectively.

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.

A comparative analysis of traditional and online lab science transfer courses in the rural community college

NASA Astrophysics Data System (ADS)

Scott, Andrea

Through distance learning, the community college system has moved beyond geographical boundaries to serve all students and provide educational opportunities at a distance to individuals previously out of reach of the college community. With the inception of the Mississippi Virtual Community College (MSVCC) in January 2000, Mississippi's public community colleges have experienced unprecedented growth in online enrollments and online course offerings to include the laboratory sciences; however, transfer of online lab science courses are problematic for individuals who wish to gain admittance to Medical, Dental, and Pharmacy schools in Mississippi. Currently online lab science courses are not accepted for transfer for students seeking admission to Mississippi Medical, Dental, or Pharmacy schools. The need for this study, the statement of the problem, and the purpose of the study address transfer issues related to the transfer of online lab science courses in Mississippi and the impact of such on the student and community college. The study also addresses existing doubts regarding online course delivery as a viable method of lab science delivery. The purpose of the study was to investigate differences between online instructional delivery as compared to traditional face-to-face delivery with the following research questions to: (1) Investigate the perception of quality of online courses as compared to traditional face-to-face courses. (2) Investigate the difference in student performance in online transfer lab science courses as compared to student performance in traditional face-to-face lab science courses. The results of this 13 semester study show significant differences in both perception of quality and student performance between online instructional delivery as compared to traditional face-to-face delivery. The findings demonstrate a need for Mississippi Dental, Medical, and Pharmacy schools to reexamine the articulation agreement between IHL and Community and Junior Colleges and consider accepting online lab sciences courses taken at the community college as transfer for admission to Medical, Dental, and Pharmacy schools. Conclusions are included in the study; however, additional studies are needed to address the issue of student performance in the online lab science classroom.

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.

Advancement in carbon nanotubes: basics, biomedical applications and toxicity.

PubMed

Beg, Sarwar; Rizwan, Mohammad; Sheikh, Asif M; Hasnain, M Saquib; Anwer, Khalid; Kohli, Kanchan

2011-02-01

Carbon nanotubes (CNTs) have attracted much attention by researchers worldwide in recent years for their small dimensions and unique architecture, and for having immense potential in nanomedicine as biocompatible and supportive substrates, as a novel tool for the delivery of therapeutic molecules including peptides, RNA and DNA, and also as sensors, actuators and composites. CNTs have been employed in the development of molecular electronic, composite materials and others due to their unique atomic structure, high surface area-to-volume ratio and excellent electronic, mechanical and thermal properties. Recently they have been exploited as novel nanocarriers in drug delivery systems and biomedical applications. Their larger inner volume as compared with the dimensions of the tube and easy immobilization of their outer surface with biocompatible materials make CNTs a superior nanomaterial for drug delivery. Literature reveals that CNTs are versatile carriers for controlled and targeted drug delivery, especially for cancer cells, because of their cell membrane penetrability. This review enlightens the biomedical application of CNTs with special emphasis on utilization in controlled and targeted drug delivery, as a diagnostics tool and other possible uses in therapeutic systems. The review also focuses on the toxicity aspects of CNTs, and revealed that genotoxic potential, mutagenic and carcinogenic effects of different types of CNTs must be explored and overcome by formulating safe biomaterial for drug delivery. The review also describes the regulatory aspects and clinical and market status of CNTs. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society.

Poster — Thur Eve — 19: Performance assessment of a 160-leaf beam collimation system

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

Ali, E. S. M.; La Russa, D. J.; Vandervoort, E.

2014-08-15

In this study, the performance of the new beam collimation system with 160 leaves, each with a 5 mm leaf width projected at isocenter, is evaluated in terms of positional accuracy and plan/delivery quality. Positional accuracy was evaluated using a set of static and dynamic MLC/jaw delivery patterns at different gantry angles, dose rates, and MLC/jaw speeds. The impact on IMRT plan quality was assessed by comparing against a previous generation collimation system using the same optimization parameters, while delivery quality was quantified using a combination of patient-specific QA measurements with ion chambers, film, and a bi-planar diode array. Positionalmore » accuracy for four separate units was comparable. The field size accuracy, junction width, and total displacement over 16 cm leaf travel are 0.3 ± 0.2 mm, 0.4 ± 0.3 mm, and 0.5 ± 0.2 mm, respectively. The typical leaf minor offset is 0.05 ± 0.04 mm, and MLC hysteresis effects are 0.2 ± 0.1 mm over 16 cm travel. The dynamic output is linear with MU and MLC/jaw speed, and is within 0.7 ± 0.3 % of the planning system value. Plan quality is significantly improved both in terms of target coverage and OAR sparing due, in part, to the larger allowable MLC and jaw speeds. γ-index pass rates for the patient-specific QA measurements exceeded 97% using criteria of 2%/2 mm. In conclusion, the performance of the Agility system is consistent among four separate installations, and is superior to its previous generations of collimation systems.« less

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection.

PubMed

Inzana, J A; Trombetta, R P; Schwarz, E M; Kates, S L; Awad, H A

2015-11-04

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

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

PubMed

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

2017-05-01

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

In-vitro and in-vivo characterization of a buprenorphine delivery system.

PubMed

Kleppner, Sofie R; Patel, Raj; McDonough, Joseph; Costantini, Lauren C

2006-03-01

Buprenorphine is a mu-opioid receptor partial agonist with enhanced safety and comparable efficacy to methadone for treatment of opioid dependence. The sublingual formulation of buprenorphine, approved for treatment of opioid dependence, produces variable buprenorphine blood levels and requires frequent dosing that limits patient compliance. To achieve stable buprenorphine levels that may improve patient outcome, an implantable sustained buprenorphine delivery system was developed. Each implant consists of ethylene vinyl acetate copolymer and 90 mg buprenorphine HCl, and measures 26 mm in length and 2.4 mm in diameter. Steady-state release in-vitro was 0.5 mg/implant/day. In-vivo pharmacokinetics and safety were examined for up to 52 weeks in beagle dogs receiving 8, 16 or 24 subcutaneous implants. Plasma buprenorphine concentrations correlated with the number of implants administered. Peak buprenorphine concentrations were generally reached within 24 h after implantation. Steady-state plasma levels were attained between 3 and 8 weeks, and were maintained for study duration, with a calculated mean release rate of 0.14+/-0.04 mg/implant/day. There were no test-article-related adverse effects. This delivery system can provide long-term stable systemic buprenorphine levels, and may increase patient compliance, thereby improving outcome for opioid-dependent patients.

Intranuclear DNA release is a determinant of transfection activity for a non-viral vector: biocleavable polyrotaxane as a supramolecularly dissociative condenser for efficient intranuclear DNA release.

PubMed

Yamada, Yuma; Nomura, Taku; Harashima, Hideyoshi; Yamashita, Atsushi; Katoono, Ryo; Yui, Nobuhiko

2010-01-01

It has been believed that nuclear gene delivery is the most important process for gene expression, and various non-viral vectors are currently being developed with this assumption. However, some of our earlier studies revealed a surprising difference in transfection activity between viral and non-viral vectors: this difference is largely due to the result of the intranuclear disposition of DNA rather than its delivery to the nucleus (Hama S. et al. (2006), Quantitative comparison of intracellular trafficking and nuclear transcription between adenoviral and lipoplex systems. Mol. Ther., 13, 786-794). Here, we report on some direct evidence that demonstrates the importance of the release of intranuclear DNA on transfection activity. The data show that transfection activity can be substantially enhanced by integrating a multifunctional envelope-type nano device (MEND) and a biocleavable polyrotaxane (DMAE-SS-PRX) as an artificial condenser. Our integration system showed significantly higher transfection activity compared to conventional gene delivery system. Moreover, this system provides a strong support for our hypothesis that intranuclear DNA disposition plays a critical role in gene expression for non-viral vectors.

Assembled modules technology for site-specific prolonged delivery of norfloxacin.

PubMed

Oliveira, Paulo Renato; Bernardi, Larissa Sakis; Strusi, Orazio Luca; Mercuri, Salvatore; Segatto Silva, Marcos A; Colombo, Paolo; Sonvico, Fabio

2011-02-28

The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for individual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability. Copyright © 2010. Published by Elsevier B.V.

Laser beam alignment and profilometry using diagnostic fluorescent safety mirrors

NASA Astrophysics Data System (ADS)

Lizotte, Todd E.

2011-03-01

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

Using a MOOC Format for a Precalculus Course

ERIC Educational Resources Information Center

Townsley, Lisa

2016-01-01

We describe recent attempts by the University System of Georgia to develop and pilot a system-wide online Precalculus course for credit. The course was based on full online delivery, using an emporium model for learning. We experienced moderate success with the course, with a completion rate of 61-76% compared with the 4-7% for Massive Open Online…

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.

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

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

A Comparative Evaluation of Hydroxycamptothecin Drug Nanorods With and Without Methotrexate Prodrug Functionalization for Drug Delivery

NASA Astrophysics Data System (ADS)

Guo, Fuqiang; Fan, Zhongxiong; Yang, Jinbin; Li, Yang; Wang, Yange; Zhao, Hai; Xie, Liya; Hou, Zhenqing

2016-08-01

We developed a novel self-targeted multi-drug co-delivery system based on rod-shaped 10-hydroxycamptothecin (CPT) nanoanticancer drug (CPT NRs) followed by a surface functionalization with self-targeting PEGylated lipid-conjugated methotrexate (MTX) pro-anticancer drug. The self-targeting effect and in vitro cell viability of the MTX-PEG-CPT NRs on HeLa cells were demonstrated by comparative cellular uptake and MTT assay of the PEG-CPT NRs. In vitro studies showed the feasibility of using this high drug-loading MTX-PEG-CPT NRs in self-targeted drug delivery, controlled-/sustained-release, and synergistic cancer therapy. More importantly, this work would stimulate interest in the use of PEGylated lipid-conjugated MTX by introducing an early-phase tumor-targeting role and then driving a late-phase anticancer role for the highly convergent design of nanomulti-drug, which may advantageously offer a new and simple strategy for simultaneously targeting and treating FA receptor-overexpressing cancer cells.

A global health delivery framework approach to epilepsy care in resource-limited settings.

PubMed

Cochran, Maggie F; Berkowitz, Aaron L

2015-11-15

The Global Health Delivery (GHD) framework (Farmer, Kim, and Porter, Lancet 2013;382:1060-69) allows for the analysis of health care delivery systems along four axes: a care delivery value chain that incorporates prevention, diagnosis, and treatment of a medical condition; shared delivery infrastructure that integrates care within existing healthcare delivery systems; alignment of care delivery with local context; and generation of economic growth and social development through the health care delivery system. Here, we apply the GHD framework to epilepsy care in rural regions of low- and middle-income countries (LMIC) where there are few or no neurologists. Copyright © 2015 Elsevier B.V. All rights reserved.

Delivery after external cephalic version, is there an increased rate of cesarian section?

PubMed

Lago Leal, Victor; Pradillo Aramendi, Tamara; Nicolas Montero, Estefania; Ocaña Martínez, Vanesa; Del Barrio Fernández, Pablo; Martínez-Cortés, Luis

2016-04-01

The aim of this study was to compare the obstetric outcomes after successful external cephalic version (cases) with a group of pregnant women with a spontaneous cephalic fetal position at delivery (controls). Retrospective review of the cohort of study was performed at the University Hospital of Getafe (Madrid, Spain) between January 2012 and January 2013. 1516 patients (48 cases; 1468 controls). We compared the type of delivery in pregnant women after ECV performed successfully (cases) with spontaneous cephalic presentations (controls). Pregnancies with vaginal delivery contraindicated, elective cesarean section (CS) justified by maternal disease, multiple pregnancies, or pregnancies below 37 weeks were excluded. Maternal age, BMI, parity, gestational age at delivery, and onset of labor (spontaneous or induced) were controlled. Prevalence of CS and operative delivery in both groups. Women who underwent a successful ECV had a significantly higher CS rate compared with the women of the control group (12/48 [25%] vs. 202/1468 [13.76%]; P=0.028). There was no difference in the rate of operative delivery (6/48 [12.5%] vs. 177/1468 [12.05%] P=0.92). Deliveries following a successful ECV are associated with an increased CS rate compared with deliveries of fetuses with spontaneous cephalic presentations.

Sensitivity Analysis of Algan/GAN High Electron Mobility Transistors to Process Variation

DTIC Science & Technology

2008-02-01

delivery system gas panel including both hydride and alkyl delivery modules and the vent/valve configurations [14...Reactor Gas Delivery Systems A basic schematic diagram of an MOCVD reactor delivery gas panel is shown in Figure 13. The reactor gas delivery...system, or gas panel , consists of a network of stainless steel tubing, automatic valves and electronic mass flow controllers (MFC). There are separate

Long-term single-center experience of defibrillator therapy in children and adolescents.

PubMed

Frommeyer, Gerrit; Feder, Sebastian; Bettin, Markus; Debus, Volker; Köbe, Julia; Reinke, Florian; Uebing, Anselm; Eckardt, Lars; Kehl, Hans Gerd

2018-06-01

Implantable cardioverter-defibrillator (ICD) systems are established therapy for prevention of sudden cardiac death. Long-term data on ICD systems in children and adolescents is rare. The present study displays a long-term single-center follow-up of children and adolescents with ICD systems. The present study represents a single-center experience of patients younger than 18 years who received an ICD (n = 58). Follow-up data included in-house follow-up as well as examinations of collaborating specialists. Mean age at implantation was 14.0 ± 3.3 years and 33 patients (56.9%) were male. A transvenous ICD system was implanted in 54 patients (93.1%). In 33 patients (56.9%) electrical heart disease or idiopathic ventricular fibrillation represented the underlying condition of ICD implantation. Median follow-up duration was 70 months (45; 94). 3 patients (5.2%) died during the observation period. None of these deaths was associated with ICD failure. Appropriate shocks occurred in 32 patients (55.2%). Inappropriate shock delivery was recorded in 17 patients (29.3%). Supraventricular tachycardia represented the most frequent cause of inappropriate shock delivery (9 patients, 52.9%). T-wave oversensing led to inappropriate shock delivery in 3 patients (17.6%). In 5 patients (29.4%), lead failure caused inappropriate shock delivery. Of note, during follow-up lead failure was reported in 15 patients (25.9%) leading to surgical revision. ICD therapy in children and adolescents is effective for prevention of sudden cardiac death. The rate of appropriate shock deliveries was significantly higher as compared with large ICD trials. Inappropriate therapies occurred frequently. In particular supraventricular tachycardia, T-wave oversensing and lead failures were responsible for these episodes. Copyright © 2017 Elsevier B.V. All rights reserved.

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 of valves. Varying amounts of drugs, together with more complex controlling strategies would allow creation of more complex drug delivery patterns.

SU-E-T-350: Verification of Gating Performance of a New Elekta Gating Solution: Response Kit and Catalyst System

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

Xie, X; Cao, D; Housley, D

2014-06-01

Purpose: In this work, we have tested the performance of new respiratory gating solutions for Elekta linacs. These solutions include the Response gating and the C-RAD Catalyst surface mapping system.Verification measurements have been performed for a series of clinical cases. We also examined the beam on latency of the system and its impact on delivery efficiency. Methods: To verify the benefits of tighter gating windows, a Quasar Respiratory Motion Platform was used. Its vertical-motion plate acted as a respiration surrogate and was tracked by the Catalyst system to generate gating signals. A MatriXX ion-chamber array was mounted on its longitudinal-movingmore » platform. Clinical plans are delivered to a stationary and moving Matrix array at 100%, 50% and 30% gating windows and gamma scores were calculated comparing moving delivery results to the stationary result. It is important to note that as one moves to tighter gating windows, the delivery efficiency will be impacted by the linac's beam-on latency. Using a specialized software package, we generated beam-on signals of lengths of 1000ms, 600ms, 450ms, 400ms, 350ms and 300ms. As the gating windows get tighter, one can expect to reach a point where the dose rate will fall to nearly zero, indicating that the gating window is close to beam-on latency. A clinically useful gating window needs to be significantly longer than the latency for the linac. Results: As expected, the use of tighter gating windows improved delivery accuracy. However, a lower limit of the gating window, largely defined by linac beam-on latency, exists at around 300ms. Conclusion: The Response gating kit, combined with the C-RAD Catalyst, provides an effective solution for respiratorygated treatment delivery. Careful patient selection, gating window design, even visual/audio coaching may be necessary to ensure both delivery quality and efficiency. This research project is funded by Elekta.« less

Internet infrastructures and health care systems: a qualitative comparative analysis on networks and markets in the British National Health Service and Kaiser Permanente.

PubMed

Séror, Ann C

2002-12-01

The Internet and emergent telecommunications infrastructures are transforming the future of health care management. The costs of health care delivery systems, products, and services continue to rise everywhere, but performance of health care delivery is associated with institutional and ideological considerations as well as availability of financial and technological resources. to identify the effects of ideological differences on health care market infrastructures including the Internet and telecommunications technologies by a comparative case analysis of two large health care organizations: the British National Health Service and the California-based Kaiser Permanente health maintenance organization. A qualitative comparative analysis focusing on the British National Health Service and the Kaiser Permanente health maintenance organization to show how system infrastructures vary according to market dynamics dominated by health care institutions ("push") or by consumer demand ("pull"). System control mechanisms may be technologically embedded, institutional, or behavioral. The analysis suggests that telecommunications technologies and the Internet may contribute significantly to health care system performance in a context of ideological diversity. The study offers evidence to validate alternative models of health care governance: the national constitution model, and the enterprise business contract model. This evidence also suggests important questions for health care policy makers as well as researchers in telecommunications, organizational theory, and health care management.

Internet Infrastructures and Health Care Systems: a Qualitative Comparative Analysis on Networks and Markets in the British National Health Service and Kaiser Permanente

PubMed Central

2002-01-01

Background The Internet and emergent telecommunications infrastructures are transforming the future of health care management. The costs of health care delivery systems, products, and services continue to rise everywhere, but performance of health care delivery is associated with institutional and ideological considerations as well as availability of financial and technological resources. Objective To identify the effects of ideological differences on health care market infrastructures including the Internet and telecommunications technologies by a comparative case analysis of two large health care organizations: the British National Health Service and the California-based Kaiser Permanente health maintenance organization. Methods A qualitative comparative analysis focusing on the British National Health Service and the Kaiser Permanente health maintenance organization to show how system infrastructures vary according to market dynamics dominated by health care institutions ("push") or by consumer demand ("pull"). System control mechanisms may be technologically embedded, institutional, or behavioral. Results The analysis suggests that telecommunications technologies and the Internet may contribute significantly to health care system performance in a context of ideological diversity. Conclusions The study offers evidence to validate alternative models of health care governance: the national constitution model, and the enterprise business contract model. This evidence also suggests important questions for health care policy makers as well as researchers in telecommunications, organizational theory, and health care management. PMID:12554552

Constructive Student Feedback: Online vs. Traditional Course Evaluations

ERIC Educational Resources Information Center

Donovan, Judy; Mader, Cynthia E.; Shinsky, John

2010-01-01

Substantial efforts have been made recently to compare the effectiveness of traditional course formats to alternative formats (most often, online delivery compared to traditional on-site delivery). This study examines, not the delivery format but rather the evaluation format. It compares traditional paper and pencil methods for course evaluation…

Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and Transdermal Application.

PubMed

Jain, Shashank; Patel, Niketkumar; Shah, Mansi K; Khatri, Pinak; Vora, Namrata

2017-02-01

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid-based delivery systems (vesicular carriers and lipid particulate systems) have been the most successful. Vesicular carriers consist of liposomes, ultradeformable liposomes, and ethosomes, while lipid particulate systems consist of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers. These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Intrauterine device insertion in the postpartum period: a systematic review.

PubMed

Sonalkar, Sarita; Kapp, Nathalie

2015-02-01

Given new research on postpartum placement of levonorgestrel and copper intrauterine devices (IUDs), our objective was to update a prior systematic review of the safety and expulsion rates of postpartum IUDs. We searched MEDLINE, CENTRAL, LILACS, POPLINE, Web of Science, and ClinicalTrials.gov databases for articles between the database inception until July 2013. We included studies that compared IUD insertion time intervals and routes during the postpartum period. We used standard abstract forms and the United States Preventive Services Task Force grading system to summarise and assess the quality of the evidence. We included 18 articles. New evidence suggests that a levonorgestrel releasing-intrauterine system (LNG-IUS) insertion within 48 hours of delivery is safe. Postplacental insertion and insertion between 10 minutes and 48 hours after delivery result in higher expulsion rates than insertion 4 to 6 weeks postpartum, or non-postpartum insertion. Insertion at the time of caesarean section is associated with lower expulsion rates than postplacental insertion at the time of vaginal delivery. This review supports the evidence that insertion of an intrauterine contraceptive within the first 48 hours of vaginal or caesarean delivery is safe. Expulsion rates should be further studied in larger randomised controlled trials.

Poly(acrylic acid)/polyethylene glycol hygrogel prepared by using gamma-ray irradiation for mucosa adhesion

NASA Astrophysics Data System (ADS)

Nho, Young-Chang; Park, Jong-Seok; Shin, Jung-Woong; Lim, Youn-Mook; Jeong, Sung-In; Shin, Young-Min; Gwon, Hui-Jeong; Khil, Myung-Seob; Lee, Deok-Won; Ahn, Sung-Jun

2015-01-01

A buccal delivery system provides a much milder environment for drug delivery compared to an oral delivery which presents a hostile environment for drugs, especially proteins and polypeptides, owing to acid hydrolysis. Local delivery in an oral cavity has particular applications in the treatment of toothaches, periodontal disease, and bacterial infections. Poly(acrylic acid) (PAA)-based hydrogels prepared using a chemical initiator have been attempted for a mucoadhesive system owing to their flexibility and excellent bioadhesion. In this experiment, PAA and polyethylene glycol (PEG) were selected to prepare using a radiation process a bioadhesive hydrogel for adhesion to mucosal surfaces. PAA and PEG were dissolved in purified water to prepare a homogeneous PAA/PEG solution, and the solution was then irradiated using an electron beam at dose up to 70 kGy to make the hydrogels. Their physical properties, such as gel percent, swelling percent, and adhesive strength to mucosal surfaces, were investigated. In this experiment, various amounts of PEG were incorporated into the PAA to enhance the mucoadhesive property of the hydrogels. The effect of the molecular weight of PEG on the mucoadhesion was also examined.

Management of three-dimensional intrafraction motion through real-time DMLC tracking.

PubMed

Sawant, Amit; Venkat, Raghu; Srivastava, Vikram; Carlson, David; Povzner, Sergey; Cattell, Herb; Keall, Paul

2008-05-01

Tumor tracking using a dynamic multileaf collimator (DMLC) represents a promising approach for intrafraction motion management in thoracic and abdominal cancer radiotherapy. In this work, we develop, empirically demonstrate, and characterize a novel 3D tracking algorithm for real-time, conformal, intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based radiation delivery to targets moving in three dimensions. The algorithm obtains real-time information of target location from an independent position monitoring system and dynamically calculates MLC leaf positions to account for changes in target position. Initial studies were performed to evaluate the geometric accuracy of DMLC tracking of 3D target motion. In addition, dosimetric studies were performed on a clinical linac to evaluate the impact of real-time DMLC tracking for conformal, step-and-shoot (S-IMRT), dynamic (D-IMRT), and VMAT deliveries to a moving target. The efficiency of conformal and IMRT delivery in the presence of tracking was determined. Results show that submillimeter geometric accuracy in all three dimensions is achievable with DMLC tracking. Significant dosimetric improvements were observed in the presence of tracking for conformal and IMRT deliveries to moving targets. A gamma index evaluation with a 3%-3 mm criterion showed that deliveries without DMLC tracking exhibit between 1.7 (S-IMRT) and 4.8 (D-IMRT) times more dose points that fail the evaluation compared to corresponding deliveries with tracking. The efficiency of IMRT delivery, as measured in the lab, was observed to be significantly lower in case of tracking target motion perpendicular to MLC leaf travel compared to motion parallel to leaf travel. Nevertheless, these early results indicate that accurate, real-time DMLC tracking of 3D tumor motion is feasible and can potentially result in significant geometric and dosimetric advantages leading to more effective management of intrafraction motion.

A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells

PubMed Central

Gonzalez Porras, Maria A.; Durfee, Paul N.; Gregory, Ashley M.; Sieck, Gary C.; Brinker, C. Jeffrey; Mantilla, Carlos B.

2017-01-01

Background Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions. New method We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes. Results CTB modified protocells showed significantly greater motoneuron uptake compared to unmodified protocells after 24 h of treatment (60% vs. 15%, respectively). CTB-protocells showed specific uptake by motoneurons compared to muscle cells and demonstrated cargo release of a surrogate drug. Protocells showed a lack of cytotoxicity and unimpaired cellular proliferation. In isolated diaphragm muscle-phrenic nerve preparations, preferential axon terminal uptake of CTB-modified protocells was observed compared to uptake in surrounding muscle tissue. A larger proportion of axon terminals displayed uptake following treatment with CTB-protocells compared to unmodified protocells (40% vs. 6%, respectively). Comparison with existing method(s) Current motoneuron targeting strategies lack the functionality to load and deliver multiple cargos. CTB-protocells capitalizes on the advantages of liposomes and mesoporous silica nanoparticles allowing a large loading capacity and cargo release. The ability of CTB-protocells to target motoneurons at the NMJ confers a great advantage over existing methods. Conclusions CTB-protocells constitute a viable targeted motoneuron delivery system for drugs and genes facilitating various therapies for neuromuscular diseases. PMID:27641118

A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells.

PubMed

Gonzalez Porras, Maria A; Durfee, Paul N; Gregory, Ashley M; Sieck, Gary C; Brinker, C Jeffrey; Mantilla, Carlos B

2016-11-01

Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, ageing, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions. We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes. CTB modified protocells showed significantly greater motoneuron uptake compared to unmodified protocells after 24h of treatment (60% vs. 15%, respectively). CTB-protocells showed specific uptake by motoneurons compared to muscle cells and demonstrated cargo release of a surrogate drug. Protocells showed a lack of cytotoxicity and unimpaired cellular proliferation. In isolated diaphragm muscle-phrenic nerve preparations, preferential axon terminal uptake of CTB-modified protocells was observed compared to uptake in surrounding muscle tissue. A larger proportion of axon terminals displayed uptake following treatment with CTB-protocells compared to unmodified protocells (40% vs. 6%, respectively). Current motoneuron targeting strategies lack the functionality to load and deliver multiple cargos. CTB-protocells capitalizes on the advantages of liposomes and mesoporous silica nanoparticles allowing a large loading capacity and cargo release. The ability of CTB-protocells to target motoneurons at the NMJ confers a great advantage over existing methods. CTB-protocells constitute a viable targeted motoneuron delivery system for drugs and genes facilitating various therapies for neuromuscular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

[Analysis of the Effect of Non-phacoemulsification Cataract Operation on Corneal Endothelial Cell Nucleus Division].

PubMed

Huang, Zufeng; Miao, Xiaoqing

2015-09-01

To investigate the effect of non-phacoemulsification cataract operation in two different patterns of nucleus delivery on the quantity and morphology of corneal endothelial cells and postoperative visual acuity. Forty patients diagnosed with cataract underwent cataract surgery and were assigned into the direct nuclear delivery and semi-nuclear delivery groups. Lens density was measured and divided into the hard and soft lenses according to Emery-little lens nucleus grading system. Non-phacoemulsification cataract operation was performed. At 3 d after surgery, the quantity and morphology of corneal endothelium were counted and observed under corneal endothelial microscope. During 3-month postoperative follow-up, the endothelial cell loss rate, morphological changes and visual acuity were compared among four groups. Corneal endothelial cell loss rate in the direct delivery of hard nucleus group significantly differed from those in the other three groups before and 3 months after operation (P < 0.01), whereas no statistical significance was found among the direct delivery of soft nucleus, semi-delivery of hard nucleus and semi-delivery soft nucleus groups (all P > 0.05). Preoperative and postoperative 2-d visual acuity did not differ between the semi-delivery of hard nucleus and direct delivery of soft nucleus groups (P = 0.49), significantly differed from those in the semi-delivery of soft nucleus (P = 0.03) and direct delivery of hard nucleus groups (P = 0.14). Visual acuity at postoperative four months did not differ among four groups (P = 0.067). During non-phacoemulsification cataract surgery, direct delivery of hard nucleus caused severe injury to corneal endothelium and semi-delivery of soft nucleus yielded mild corneal endothelial injury. Slight corneal endothelial injury exerted no apparent effect upon visual acuity and corneal endothelial morphology at three months after surgery.

A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.

PubMed

Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; van Damme, Pierre

2016-10-17

Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

Singla, Sumeet K; Sachdeva, Vishal

2015-01-01

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

Induction of a robust immune response against avian influenza virus following transdermal inoculation with H5-DNA vaccine formulated in modified dendrimer-based delivery system in mouse model.

PubMed

Bahadoran, Azadeh; Ebrahimi, Mehdi; Yeap, Swee Keong; Safi, Nikoo; Moeini, Hassan; Hair-Bejo, Mohd; Hussein, Mohd Zobir; Omar, Abdul Rahman

2017-01-01

This study was aimed to evaluate the immunogenicity of recombinant plasmid deoxyribonucleic acid (DNA), pBud-H5-green fluorescent protein (GFP)-interferon-regulatory factor (IRF)3 following delivery using polyamidoamine (PAMAM) dendrimer and transactivator of transcription (TAT)-conjugated PAMAM dendrimer as well as the effect of IRF3 as the genetic adjuvant. BALB/c mice were vaccinated transdermally with pBud-H5-GFP, PAMAM/pBud-H5-GFP, TAT-PAMAM/pBud-H5-GFP, and TAT-PAMAM/pBud-H5-GFP-IRF3. The expression analysis of H5 gene from the blood by using quantitative real-time reverse transcriptase polymerase chain reaction confirmed the ability of PAMAM dendrimer as a carrier for gene delivery, as well as the ability of TAT peptide to enhance the delivery efficiency of PAMAM dendrimer. Mice immunized with modified PAMAM by TAT peptide showed higher hemagglutination inhibition titer, and larger CD3 + /CD4 + T cells and CD3 + /CD8 + T cells population, as well as the production of cytokines, namely, interferon (IFN)-γ, interleukin (IL)-2, IL-15, IL-12, IL-6, and tumor necrosis factor-α compared with those immunized with native PAMAM. These results suggest that the function of TAT peptide as a cell-penetrating peptide is able to enhance the gene delivery, which results in rapid distribution of H5 in the tissues of the immunized mice. Furthermore, pBud-H5-GFP co-expressing IRF3 as a genetic adjuvant demonstrated the highest hemagglutination inhibition titer besides larger CD3 + /CD4 + and CD3 + /CD8 + T cells population, and strong Th1-like cytokine responses among all the systems tested. In conclusion, TAT-PAMAM dendrimer-based delivery system with IRF3 as a genetic adjuvant is an attractive transdermal DNA vaccine delivery system utilized to evaluate the efficacy of the developed DNA vaccine in inducing protection during challenge with virulent H5N1 virus.

Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides.

PubMed

Batista, Patrícia; Castro, Pedro M; Madureira, Ana Raquel; Sarmento, Bruno; Pintado, Manuela

2018-03-01

Bioactive proteins and peptides have been used with either prophylactic or therapeutic purposes, presenting inherent advantages as high specificity and biocompatibility. Nanocarriers play an important role in the stabilization of proteins and peptides, offering enhanced buccal permeation and protection while crossing the gastrointestinal tract. Moreover, preparation of nanoparticles as oral delivery systems for proteins/peptides may include tailored formulation along with functionalization aiming bioavailability enhancement of carried proteins or peptides. Oral delivery systems, namely buccal delivery systems, represent an interesting alternative route to parenteric delivery systems to carry proteins and peptides, resulting in higher comfort of administration and, therefore, compliance to treatment. This paper outlines an extensive overview of the existing publications on proteins/peptides oral nanocarriers delivery systems, with special focus on buccal route. Manufacturing aspects of most commonly used nanoparticles for oral delivery (e.g. polymeric nanoparticles using synthetic or natural polymers and lipid nanoparticles) advantages and limitations and potential applications of nanoparticles as proteins/peptides delivery systems will also be thoroughly addressed. Copyright © 2018 Elsevier Inc. All rights reserved.

Online 3D EPID-based dose verification: Proof of concept.

PubMed

Spreeuw, Hanno; Rozendaal, Roel; Olaciregui-Ruiz, Igor; González, Patrick; Mans, Anton; Mijnheer, Ben; van Herk, Marcel

2016-07-01

Delivery errors during radiotherapy may lead to medical harm and reduced life expectancy for patients. Such serious incidents can be avoided by performing dose verification online, i.e., while the patient is being irradiated, creating the possibility of halting the linac in case of a large overdosage or underdosage. The offline EPID-based 3D in vivo dosimetry system clinically employed at our institute is in principle suited for online treatment verification, provided the system is able to complete 3D dose reconstruction and verification within 420 ms, the present acquisition time of a single EPID frame. It is the aim of this study to show that our EPID-based dosimetry system can be made fast enough to achieve online 3D in vivo dose verification. The current dose verification system was sped up in two ways. First, a new software package was developed to perform all computations that are not dependent on portal image acquisition separately, thus removing the need for doing these calculations in real time. Second, the 3D dose reconstruction algorithm was sped up via a new, multithreaded implementation. Dose verification was implemented by comparing planned with reconstructed 3D dose distributions delivered to two regions in a patient: the target volume and the nontarget volume receiving at least 10 cGy. In both volumes, the mean dose is compared, while in the nontarget volume, the near-maximum dose (D2) is compared as well. The real-time dosimetry system was tested by irradiating an anthropomorphic phantom with three VMAT plans: a 6 MV head-and-neck treatment plan, a 10 MV rectum treatment plan, and a 10 MV prostate treatment plan. In all plans, two types of serious delivery errors were introduced. The functionality of automatically halting the linac was also implemented and tested. The precomputation time per treatment was ∼180 s/treatment arc, depending on gantry angle resolution. The complete processing of a single portal frame, including dose verification, took 266 ± 11 ms on a dual octocore Intel Xeon E5-2630 CPU running at 2.40 GHz. The introduced delivery errors were detected after 5-10 s irradiation time. A prototype online 3D dose verification tool using portal imaging has been developed and successfully tested for two different kinds of gross delivery errors. Thus, online 3D dose verification has been technologically achieved.

The effectiveness of the controlled release of simvastatin from β-TCP macrosphere in the treatment of OVX mice.

PubMed

Chou, Joshua; Ito, Tomoko; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce

2016-03-01

Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side-effects. Given the associated side-effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta-tricalcium phosphate (β-TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β-TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the release of simvastatin, an apatite coating was made around the β-TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β-TCP, β-TCP with simvastatin, apatite-coated β-TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non-implanted side (left) and showed that β-TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite-coated β-TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its release can be prolonged with an apatite coating to significantly promote relevant bone formation. Copyright © 2013 John Wiley & Sons, Ltd.

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

PubMed

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-06-01

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

PubMed

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-08-11

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

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

PubMed

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

2015-10-01

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

A minocycline-releasing PMMA system as a space maintainer for staged bone reconstructions-in vitro antibacterial, cytocompatibility and anti-inflammatory characterization.

PubMed

Silva, Tiago; Grenho, Liliana; Barros, Joana; Silva, José Carlos; Pinto, Rosana V; Matos, Ana; Colaço, Bruno; Fernandes, Maria Helena; Bettencourt, Ana; Gomes, Pedro S

2017-06-06

In the present work, we study the development and biological characterization of a polymethyl methacrylate (PMMA)-based minocycline delivery system, to be used as a space maintainer within craniofacial staged regenerative interventions. The developed delivery systems were characterized regarding solid state characteristics and assayed in vitro for antibacterial and anti-inflammatory activity, and cytocompatibility with human bone cells. A drug release profile allowed for an initial burst release and a more sustained and controlled release over time, with minimum inhibitory concentrations for the assayed and relevant pathogenic bacteria (i.e., Staphylococcus aureus, slime-producer Staphylococcus epidermidis and Escherichia coli) being easily attained in the early time points, and sustained up to 72 h. Furthermore, an improved osteoblastic cell response-with enhancement of cell adhesion and cell proliferation-and increased anti-inflammatory activity were verified in developed systems, compared to a control (non minocycline-loaded PMMA cement). The obtained results converge to support the possible efficacy of the developed PMMA-based minocycline delivery systems for the clinical management of complex craniofacial trauma. Here, biomaterials with space maintenance properties are necessary for the management of staged reconstructive approaches, thus minimizing the risk of peri-operative infections and enhancing the local tissue healing and early stages of regeneration.

Where are we on the diffusion curve? Trends and drivers of primary care physicians' use of health information technology.

PubMed

Audet, Anne-Marie; Squires, David; Doty, Michelle M

2014-02-01

To describe trends in primary care physicians' use of health information technology (HIT) between 2009 and 2012, examine practice characteristics associated with greater HIT capacity in 2012, and explore factors such as delivery system and payment reforms that may affect adoption and functionality. We used data from the 2012 and 2009 Commonwealth Fund International Health Policy Surveys of Primary Care Physicians. The data were collected in both years by postal mail between March and July among a nationally representative sample of primary care physicians in the United States. We compared primary care physicians' HIT capacity in 2009 and 2012. We employed multivariable logistic regression to analyze whether participating in an integrated delivery system, sharing resources and support with other practices, and being eligible for financial incentives were associated with greater HIT capacity in 2012. Primary care physicians' HIT capacity has significantly expanded since 2009, although solo practices continue to lag. Practices that are part of an integrated delivery system or share resources with other practices have higher rates of electronic medical record (EMR) adoption, multifunctional HIT, electronic information exchange, and electronic access for patients. Receiving or being eligible for financial incentives is associated with greater adoption of EMRs and information exchange. Federal efforts to increase adoption have coincided with a rapid increase in HIT capacity. Delivery system and payment reforms and federally funded extension programs could offer promising pathways for further diffusion. © Health Research and Educational Trust.

Development of self-nanoemulsifying drug delivery system for oral bioavailability enhancement of valsartan in beagle dogs.

PubMed

Li, Zhenbao; Zhang, Wenjuan; Gao, Yan; Xiang, Rongwu; Liu, Yan; Hu, Mingming; Zhou, Mei; Liu, Xiaohong; Wang, Yongjun; He, Zhonggui; Sun, Yinghua; Sun, Jin

2017-02-01

Valsartan, an angiotensin II receptor antagonist, is widely used to treat high blood pressure in the clinical setting. However, its poor water solubility results in the low oral bioavailability. The aim of this study was to improve dissolution rate and oral bioavailability by developing a self-nanoemulsifying drug delivery system. Saturation solubility of valsartan in various oils, surfactants, and cosurfactants was investigated, and the optimized formulation was determined by central composite design-response surface methodology. The shape of resultant VAL-SNEDDS was spherical with an average diameter of about 27 nm. And the drug loading efficiency is approximately 14 wt%. Differential scanning calorimetry and XRD studies disclosed the molecular or amorphous state of valsartan in VAL-SNEDDS. The dissolution study indicated that the self-nanoemulsifying drug delivery systems (SNEDDS) exhibited significantly enhanced dissolution compared with market capsules (Diovan®) in various media. Furthermore, the stability of formulation revealed that valsartan SNEDDS was stable under low temperature and accelerated test condition. Furthermore, the pharmacokinetics demonstrated that C max and AUC (0-∞) of SNEDDS capsules were about three- and twofold higher than Diovan® in beagle dogs, respectively. Meanwhile, the safety evaluation implied that VAL-SNEDDS was innocuous to beagle dogs during 15 days of continuous administration. Our results suggested that VAL-SNEDDS was a potential and safe delivery system with enhanced dissolution rate and oral bioavailability, as well as offered a strategy for the engineering of poorly water-soluble drugs in the clinical setting.

Women's antenatal preferences for delivery route in a setting with high cesarean section rates and a medically dominated maternity system.

PubMed

Dweik, Diána; Girasek, Edmond; Töreki, Annamária; Mészáros, Gyula; Pál, Attila

2014-04-01

To assess birth preferences in a sample of Hungarian pregnant women and identify determinants of ambivalence or clear choices for cesarean section throughout pregnancy. Follow-up two-point questionnaire survey. University Department of Obstetrics and Gynecology in Hungary. A total of 413 women with singleton pregnancies where there was no awareness of medical contradictions to vaginal delivery, attending for routine ultrasound examination in mid-pregnancy from November 2011 to March 2012. Questionnaires completed in mid- and late pregnancy (gestational weeks 18-22 and 35-37) including the Wijma Delivery Expectancy/Experience Questionnaire A. Prevalence of women preferring cesarean section or being uncertain about what delivery route to choose, in case they had the choice; their demographic characteristics, attitudes toward birth issues and their Wijma Delivery Expectancy/Experience Questionnaire A scores, compared with women consistent in their preference for vaginal delivery. Of the 413 respondents, 365 (88.4%) were consistent in their preference for vaginal delivery. In logistic regression models the important contributors to describing preferences for cesarean section or uncertain preferences were previous cesarean section and maternal belief that cesarean section is more beneficial than vaginal delivery. The majority of pregnant women preferred vaginal delivery to cesarean section. Neither a higher Wijma Delivery Expectancy/Experience Questionnaire A score nor sociodemographic differences were important determinants of a preference for cesarean section or for an uncertain preference. On the other hand, previous cesarean section and certain preconceived maternal attitudes towards delivery were characteristic for these women. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Pressurized vascular systems for self-healing materials

PubMed Central

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

2012-01-01

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

In vivo evaluation of drug delivery after ultrasound application: A new use for the photoacoustic technique

NASA Astrophysics Data System (ADS)

Barja, P. R.; Acosta-Avalos, D.; Rompe, P. C. B.; Dos Anjos, F. H.; Marciano, F. R.; da Silva, M. D.

2005-06-01

Ultrasound application is a therapeutical resource widely employed in physiotherapy. One of its applications is the phonophoresis, a technique in which the ultrasound radiation is utilized to deliver drugs through the skin to soft tissues. The proposal of our study was to employ the Photoacoustic Technique to evaluate the efficacy of such treatment, analyzing if phonophoresis could enhance drug delivery through skin when compared to the more traditional method of manual massage. The configuration of the system employed was such that it was possible to perform in vivo measurements, which is a pre-requisite for this kind of study. The changes observed in the photoacoustic signal amplitude after each form of drug application were attributed to changes in the thermal effusivity of the system, due to penetration of the drug. The technique was able to detect differences in drug delivery between the specified physiotherapy treatments, indicating that phonophoresis enhances drug absorption by tissue.

Water-soluble polymers bearing phosphorylcholine group and other zwitterionic groups for carrying DNA derivatives.

PubMed

Lin, Xiaojie; Ishihara, Kazuhiko

2014-01-01

Water-soluble polymers with equal positive and negative charges in the same monomer unit, such as the phosphorylcholine group and other zwitterionic groups, exhibit promising potential in gene delivery with appreciable transfection efficiency, compared with the traditional poly(ethylene glycol)-based polycation-gene complexes. These zwitterionic polymers with various architectural structures and properties have been synthesized by various polymerization methods, such as conventional radical polymerization, atom-transfer radical-polymerization, reversible addition-fragmentation chain-transfer polymerization, and nitroxide-mediated radical polymerization. These techniques have been used to efficiently facilitate gene therapy by fabrication of non-viral vectors with high cytocompatibility, large gene-carrying capacity, effective cell-membrane permeability, and in vivo gene-loading/releasing functionality. Zwitterionic polymer-based gene delivery vectors systems can be categorized into soluble-polymer/gene mixing, molecular self-assembly, and polymer-gene conjugation systems. This review describes the preparation and characterization of various zwitterionic polymer-based gene delivery vectors, specifically water-soluble phospholipid polymers for carrying gene derivatives.

Standardization of Nanoparticle Characterization: Methods for Testing Properties, Stability, and Functionality of Edible Nanoparticles.

PubMed

McClements, Jake; McClements, David Julian

2016-06-10

There has been a rapid increase in the fabrication of various kinds of edible nanoparticles for oral delivery of bioactive agents, such as those constructed from proteins, carbohydrates, lipids, and/or minerals. It is currently difficult to compare the relative advantages and disadvantages of different kinds of nanoparticle-based delivery systems because researchers use different analytical instruments and protocols to characterize them. In this paper, we briefly review the various analytical methods available for characterizing the properties of edible nanoparticles, such as composition, morphology, size, charge, physical state, and stability. This information is then used to propose a number of standardized protocols for characterizing nanoparticle properties, for evaluating their stability to environmental stresses, and for predicting their biological fate. Implementation of these protocols would facilitate comparison of the performance of nanoparticles under standardized conditions, which would facilitate the rational selection of nanoparticle-based delivery systems for different applications in the food, health care, and pharmaceutical industries.

Improving gold nanorod delivery to the central nervous system by conjugation to the shuttle Angiopep-2.

PubMed

Velasco-Aguirre, Carolina; Morales-Zavala, Francisco; Salas-Huenuleo, Edison; Gallardo-Toledo, Eduardo; Andonie, Oscar; Muñoz, Luis; Rojas, Ximena; Acosta, Gerardo; Sánchez-Navarro, Macarena; Giralt, Ernest; Araya, Eyleen; Albericio, Fernando; Kogan, Marcelo Javier

2017-10-01

To improve the in vivo delivery of gold nanorods (GNRs) to the central nervous system of rats, these gold nanoparticles were conjugated to Angiopep-2, a shuttle peptide that can cross the blood-brain barrier. GNRs were synthesized and modified using polyethylene glycol and Angiopep-2 (GNR-PEG-Angiopep-2). The physicochemical properties, in vitro cytotoxicity and ex vivo biodistribution of the conjugate were examined. GNR-PEG-Angiopep-2 was stable over the following days, and the different concentrations that were tested did not affect the viability of microvascular endothelial cells. The conjugation of Angiopep-2 to GNRs enhanced the endocytosis of these particles (in vitro) and the accumulation in brains (in vivo), when compared with GNRs modified only with PEG. This study provides evidence that Angiopep-2 improves the delivery of GNRs to the brain parenchyma. This property is highly relevant for future applications of GNRs as platforms for photothermal and theranostic purposes.

Release of Cyclic Phosphatidic Acid from Gelatin-based Hydrogels Inhibit Colon Cancer Cell Growth and Migration

PubMed Central

Tsukahara, Tamotsu; Murakami-Murofushi, Kimiko

2012-01-01

Microparticle and nanoparticle formulations are widely used to improve the bioavailability of low-solubility drugs and as vehicles for organ- and tissue-specific targeted drug delivery. We investigated the effect of a novel, controlled-release form of a bioactive lipid, cyclic phosphatidic acid (cPA), on human colon cancer cell line functions. We encapsulated cPA in gelatin-based hydrogels and examined its ability to inhibit the viability and migration of HT-29 and DLD-1 cells in vitro and the LPA-induced activity of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). The hydrogel delivery system prolonged cPA release into the culture medium. Accordingly, cPA-hydrogel microspheres substantially inhibited LPA-induced PPARγ activity and cell growth and migration compared with that of cells cultured with cPA alone. Thus, hydrogel microspheres are a potential system for stable and efficient delivery of bioactive lipids such as cPA and may offer a new strategy for targeted colon cancer treatment. PMID:23008752

Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases.

PubMed

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H F; Karla, Pradeep K; Boddu, Sai H S

2018-02-27

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.

Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

PubMed Central

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H. F.; Karla, Pradeep K.; Boddu, Sai H. S.

2018-01-01

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed. PMID:29495528

The Enhancement of Bone Allograft Incorporation by the Local Delivery of the Sphingosine 1-phosphate Receptor Targeted Drug FTY720

PubMed Central

Aronin, Caren E Petrie; Shin, Soo J; Naden, Kimberly B; Rios, Peter D; Sefcik, Lauren S; Zawodny, Sarah R; Bagayoko, Namory D; Cui, Quanjun; Khan, Yusuf

2010-01-01

Poor vascularization coupled with mechanical instability is the leading cause of post-operative complications and poor functional prognosis of massive bone allografts. To address this limitation, we designed a novel continuous polymer coating system to provide sustained localized delivery of pharmacological agent, FTY720, a selective agonist for sphingosine 1-phosphate receptors, within massive tibial defects. In vitro drug release studies validated 64% loading efficiency with complete release of compound following 14 days. Mechanical evaluation following six weeks of healing suggested significant enhancement of mechanical stability in FTY720 treatment groups compared with unloaded controls. Furthermore, superior osseous integration across the host-graft interface, significant enhancement in smooth muscle cell investment, and reduction in leukocyte recruitment was evident in FTY720 treated groups compared with untreated groups. Using this approach, we can capitalize on the existing mechanical and biomaterial properties of devitalized bone, add a controllable delivery system while maintaining overall porous structure, and deliver a small molecule compound to constitutively target vascular remodeling, osseous remodeling, and minimize fibrous encapsulation within the allograft-host bone interface. Such results support continued evaluation of drug-eluting allografts as a viable strategy to improve functional outcome and long-term success of massive cortical allograft implants. PMID:20621764

Efficacy of nano- and microemulsion-based topical gels in delivery of ibuprofen: an in vivo study.

PubMed

Azizi, Mosayeb; Esmaeili, Fariba; Partoazar, Alireza; Ejtemaei Mehr, Shahram; Amani, Amir

2017-03-01

Nanoemulsion has shown many advantages in drug delivery systems. In this study, for the first time, analgesic and anti-inflammatory properties of a nanomelusion of almond oil with and without ibuprofen was compared with corresponding microemulsion and commercial topical gel of the drug using formalin and carrageenan tests, respectively. Almond oil (oil phase) was mixed with Tween 80 and Span 80 (surfactants), and ethanol (co-surfactant) and them distilled water (aqueous phase) was then added to the mixture at once. Prepared nanoemulsions were pre-emulsified into a 100 ml beaker using magnet/stirrer (1000 rpm). Then, using a probe ultrasonicator (Hielscher UP400s, Hielscher, Ringwood, NJ) the nanoemulsions were formed. The optimised nanoemulsion formulation containing 2.5% ibuprofen, showed improved analgesic and anti-inflammatory effects compared with commercial product and corresponding microemulsion product containing 5% ibuprofen (i.e. twice the content of ibuprofen in the nanoemulsion) in vivo. The nanoemulsion preparation showed superior analgesic activities during chronic phase. Also, it decreased the inflammation from the first hour, while the microemulsion and the commercial product started to show their anti-inflammatory effects after 2 and 3 h, respectively. Our finding suggests that the size of the emulsion particles must be considered as an important factor in topical drug delivery systems.

Controlled Drug Delivery Using Microdevices

PubMed Central

Sanjay, Sharma T.; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

2016-01-01

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems. PMID:26813304

Controlled Drug Delivery Using Microdevices.

PubMed

Sanjay, Sharma T; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems.