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1

Fox Chase researchers identify a fast and more accurate treatment delivery for a robotic radiosurgery system:  

Cancer.gov

Radiosurgery is a non-invasive medical procedure in which focused beams of high-energy X-rays target tumors and other abnormalities in the body... However, some radiosurgery systems, such as the CyberKnife (CK), can be relatively time-consuming because the treatment planning requires the delivery of up to several hundred cone-shaped beams to adequately cover an irregularly shaped tumor. But a new study from Fox Chase Cancer Center now reports that there is an alternative...

2

The organization and delivery of psychological treatments.  

PubMed

This article reviews the major issues which face health providers when they seek to organise the delivery of psychological treatments to best effect. A lack of consensus on efficacy, efficiency and acceptability makes policy decisions difficult. Streamlined focused services offering evidence based interventions for a limited target group are compared with broader enterprises offering comprehensive provision of a range of therapies. The dilemmas that the relative strengths and weaknesses of these two models pose are compared in relation to setting, cost efficiency, patient acceptability, equitable access and the pragmatics of staff training, service delivery and clinical governance. It is suggested that changes in the structure of health service provision more generally and the potential inherent in new technology and innovative ways of working may provide new solutions to some of these difficulties and the successive restructurings of a department of psychological treatments are adduced as an example. PMID:17365160

Denman, Chess

2007-02-01

3

Accurate Perturbation-Variation Treatment of the Hydrogen Molecule  

Microsoft Academic Search

A Rayleigh-Schro¨dinger perturbation treatment of electron repulsion in the ground state of the hydrogen molecule is presented. The perturbation energies were accurately determined from Hylleraas-type variational principles using a 50-term basis. The perturbation series appears to converge rapidly at the equilibrium distance, in a similar fashion to the series for the united atom, helium, obtained by Scherr and Knight (1963).

Robert L. Matcha; W. Byers Brown

1968-01-01

4

Exploring targeted pulmonary delivery for treatment of lung cancer  

PubMed Central

Lung cancer is the most malignant cancer today. The treatment of lung cancer continues to be a challenge for oncologists. The direct delivery of chemotherapeutic agents to the lungs could represent a novel therapeutic approach for patients with pulmonary metastases. The large alveolar surface area, the low thickness of the epithelial barrier, and an extensive vascularization make the pulmonary route an ideal route for administration of oncolytics. This paper reviews the research performed over the last and current decades on the delivery of various oncolytics for pulmonary delivery for the treatment of lung cancer. Inhaled drug delivery devices in cancer therapy are also discussed in the present manuscript. PMID:23799201

Goel, Amit; Baboota, Sanjula; Sahni, Jasjeet K; Ali, Javed

2013-01-01

5

Periodontal disease treatment by local drug delivery.  

PubMed

The subgingival microbiologic composition of diseased periodontal sites was evaluated by darkfield microscopy before and after scaling or local delivery of tetracycline. A standardized sampling and counting method using a crevicular washing technique was developed to determine both numbers and proportions of morphotypes using darkfield microscopy. Tetracycline-loaded hollow fibers established an initial intrasulcular concentration of 200,000 micrograms/ml, which decreased exponentially to 15 micrograms/ml in 24 hours. Repetitive intrasulcular placement of these fibers at periodontitis sites produced an incremental reduction in bacterial counts over a 10-day period. Monolithic fibers made of ethylene vinyl acetate loaded with 25% tetracycline hydrochloride provided sustained release for 10 days under in vitro test conditions. Ten patients were treated in a study comparing the effects of these fibers with scaling. Fibers were placed subgingivally to fill pockets to their probable depth and covered with a periodontal dressing which was maintained for 10 days. The average intrasulcular tetracycline concentration measured at the end of the 10-day period was 643 micrograms/ml. At these sites, total counts, spirochetes, motile rods and nonmotile rods were significantly reduced immediately following treatment. Total counts were depressed to levels near the detection limit of darkfield microscopy. In comparison, scaling produced much smaller alterations of darkfield counts which were not statistically significant. PMID:3891959

Goodson, J M; Offenbacher, S; Farr, D H; Hogan, P E

1985-05-01

6

An Accurate Curved Boundary Treatment in the Lattice Boltzmann Method  

NASA Astrophysics Data System (ADS)

The lattice Boltzmann equation (LBE) is an alternative kinetic method capable of solving hydrodynamics for various systems. Major advantages of the method are due to the fact that the solution for the particle distribution functions is explicit, easy to implement, and natural to parallelize. Because the method often uses uniform regular Cartesian lattices in space, curved boundaries are often approximated by a series of stairs that leads to reduction in computational accuracy. In this work, a second-order accurate treatment of the boundary condition in the LBE method is developed for a curved boundary. The proposed treatment of the curved boundaries is an improvement of a scheme due to O. Filippova and D. Hänel (1998, J. Comput. Phys.147, 219). The proposed treatment for curved boundaries is tested against several flow problems: 2-D channel flows with constant and oscillating pressure gradients for which analytic solutions are known, flow due to an impulsively started wall, lid-driven square cavity flow, and uniform flow over a column of circular cylinders. The second-order accuracy is observed with a solid boundary arbitrarily placed between lattice nodes. The proposed boundary condition has well-behaved stability characteristics when the relaxation time is close to 1/2, the zero limit of viscosity. The improvement can make a substantial contribution toward simulating practical fluid flow problems using the lattice Boltzmann method.

Mei, Renwei; Luo, Li-Shi; Shyy, Wei

1999-11-01

7

Gated Treatment Delivery Verification With On-Line Megavoltage Fluoroscopy  

SciTech Connect

Purpose: To develop and clinically demonstrate the use of on-line real-time megavoltage (MV) fluoroscopy for gated treatment delivery verification. Methods and Materials: Megavoltage fluoroscopy (MVF) image sequences were acquired using a flat panel equipped for MV cone-beam CT in synchrony with the respiratory signal obtained from the Anzai gating device. The MVF images can be obtained immediately before or during gated treatment delivery. A prototype software tool (named RTReg4D) was developed to register MVF images with phase-sequenced digitally reconstructed radiograph images generated from the treatment planning system based on four-dimensional CT. The image registration can be used to reposition the patient before or during treatment delivery. To demonstrate the reliability and clinical usefulness, the system was first tested using a thoracic phantom and then prospectively in actual patient treatments under an institutional review board-approved protocol. Results: The quality of the MVF images for lung tumors is adequate for image registration with phase-sequenced digitally reconstructed radiographs. The MVF was found to be useful for monitoring inter- and intrafractional variations of tumor positions. With the planning target volume contour displayed on the MVF images, the system can verify whether the moving target stays within the planning target volume margin during gated delivery. Conclusions: The use of MVF images was found to be clinically effective in detecting discrepancies in tumor location before and during respiration-gated treatment delivery. The tools and process developed can be useful for gated treatment delivery verification.

Tai An, E-mail: atai@mcw.ed [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Christensen, James D.; Gore, Elizabeth [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Khamene, Ali [Imaging and Visualization Department, Siemens AG, Princeton, NJ (United States); Boettger, Thomas [Oncology Care Systems, Siemens AG, Heidelberg (Germany); Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

2010-04-15

8

Gastroretentive drug delivery systems for the treatment of Helicobacter pylori  

PubMed Central

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

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

2014-01-01

9

Cystic fibrosis: treatment with a supercomputer drug delivery model  

Microsoft Academic Search

The primary pathological manifestation of cystic fibrosis (CF) is the obstruction by mucus of biological passages throughout the body. However, all patients will develop chronic obstructive lung disease which accounts for more than 90% of CF mortality. We have used the Cray Y-MP to develop a mathematical model for targeting the delivery of inhaled pharmacologic drugs in the treatment of

X. Guan

1997-01-01

10

Substance Abuse Treatment Clinician Opinions and Infectious Disease Service Delivery  

Microsoft Academic Search

Substance abuse treatment programs are an important platform for delivery of services for infectious diseases associated with drug and alcohol use. However, important components of infectious disease care are not universally provided. Clinician training often focuses on information about infectious diseases and less attention is paid to provider opinions and attitudes that may be barriers to providing infectious diseases services.

Kathlene Tracy; Lawrence S. Brown; Steven Kritz; Donald Alderson; Jim Robinson; Edmund J. Bini; Michael Levy; Donald Calsyn; Traci Rieckmann; Bret Fuller; Pat McAuliffe; John Rotrosen

2009-01-01

11

Response to past depression treatments is not accurately recalled  

PubMed Central

Objective Assessing response to prior depression treatments is common in research and clinical practice, but few data are available regarding accuracy of recall. Data from a population-based survey were linked to electronic medical records to examine agreement between recalled treatment response and depression severity scores in medical records. Methods Electronic medical records from a large health system identified 1878 patients with two or more episodes for clinician-diagnosed depression between 2005 and 2009. 578 of those completed a survey including structured recall of response to each prior treatment – both global improvement during treatment and improvement specifically attributed to treatment. For 269 of these survey participants, at least one treatment episode could be unambiguously linked to both pre- and post-treatment PHQ9 depression scores in electronic medical records. Analyses examined agreement between patients recall of treatment response and improvement in PHQ9 scores from medical records. Results Agreement with medical records was poor both for recall of overall improvement following treatment (kappa = 0.10, 95% CI 0.00–0.19) and for recall of improvement attributed to treatment (kappa=0.12, 95% CI 0.00–0.25). Agreement remained poor when the sample was limited to medication treatment episodes, episodes lasting 3 months or more, or episodes for which the participant was “very sure” of her/his ability to recall. Agreement reached a fair level only for episodes in the six months prior to the survey (kappa = 0.23 for overall improvement, kappa = 0.36 for improvement attributed to treatment). Conclusions Patients’ recall of response to past depression treatments agrees poorly with data from medical records. Interview assessment of prior treatment response may not be a useful tool for research or clinical practice. PMID:23290322

Simon, Gregory E.; Rutter, Carolyn M.; Stewart, Christine; Pabiniak, Chester; Wehnes, Linda

2013-01-01

12

Carrier-Based Drug Delivery System for Treatment of Acne  

PubMed Central

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

Vyas, Amber; Kumar Sonker, Avinesh

2014-01-01

13

Wind-tunnel tests and modeling indicate that aerial dispersant delivery operations are highly accurate  

Technology Transfer Automated Retrieval System (TEKTRAN)

The United States Department of Agriculture’s high-speed wind tunnel facility in College Station, Texas, USA was used to determine droplet size distributions generated by dispersant delivery nozzles at wind speeds comparable to those used in aerial dispersant application. A laser particle size anal...

14

Delivery systems for the treatment of degenerated intervertebral discs.  

PubMed

The intervertebral disc (IVD) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production, abnormal enzyme activities and production of pro-inflammatory substances like cytokines. The established treatment strategy for IVD degeneration consists of physiotherapy, pain medication by drug therapy and if necessary surgery. This approach, however, has shown limited success. Alternative strategies to increase and prolong the effects of bioactive agents and to reverse the process of IVD degeneration include the use of delivery systems for drugs, proteins, cells and genes. In view of the specific anatomy and physiology of the IVD and depending on the strategy of the therapy, different delivery systems have been developed which are reviewed in this article. PMID:25451138

Blanquer, S B G; Grijpma, D W; Poot, A A

2014-10-25

15

Sustained Release Intraocular Drug Delivery Devices for Treatment of Uveitis  

PubMed Central

Corticosteroids have been the mainstay of uveitis therapy. When intraocular inflammation is unresponsive to steroids, or steroid related side effects become a concern, steroid-sparing medications may be administered which can be classified into immunosuppressive and immunomodulatory agents. Uveitis treatment can be delivered systemically, topically, periocularly or intraocularly. All of the above mentioned medications can entail significant systemic side effects, particularly if administered for prolonged durations, which may become treatment-limiting. Some medications, particularly hydrophobic compounds, may poorly cross the blood–retinal barrier. Topical medications, which have the least side effects, do not penetrate well into the posterior segment and are unsuitable for posterior uveitis which is often sight-threatening. Intraocular or periocular injections can deliver relatively high doses of drug to the eye with few or no systemic side effects. However, such injections are associated with significant complications and must often be repeated at regular intervals. Compliance with any form of regular medication can be a problem, particularly if its administration is associated with discomfort or if side effects are unpleasant. To overcome the above-mentioned limitations, an increasing number of sustained-release drug delivery devices using different mechanisms and containing a variety of agents have been developed to treat uveitis. This review discusses various current and future sustained-release ophthalmic drug delivery systems for treatment of uveitis. PMID:22454753

Haghjou, Nahid; Soheilian, Masoud; Abdekhodaie, Mohammad Jafar

2011-01-01

16

Nanovector-mediated drug delivery for spinal cord injury treatment.  

PubMed

Spinal cord injury (SCI) is the result of a traumatic primary event followed by a so-called secondary injury, which is characterized by a large spectrum of biochemical cellular pathways able to spread the lesion, worsening neurologic recovery. A growing number of potential therapeutic interventions to counteract different neurodegenerative mechanisms of SCI have been proposed, but they did not show relevant efficacy when translated as clinical treatments. Different reasons could explain these disappointing results: on one side the multifactorial evolution of SCI after the primary injury that limits the beneficial effect of just one targeted treatment and, on the other, the restricted access of pharmacological therapies to the spinal cord. For these reasons, recently, a growing interest has been shown in the development of alternative delivery strategies to administer drugs and/or biological/cellular therapies into the spine (hydrogel and nanoparticles). PMID:24845580

Caron, Ilaria; Papa, Simonetta; Rossi, Filippo; Forloni, Gianluigi; Veglianese, Pietro

2014-01-01

17

Dosimetric Impact of Interplay Effect on RapidArc Lung Stereotactic Treatment Delivery  

SciTech Connect

Purpose: Volumetric modulated arc therapy (RapidArc; Varian Medical Systems, Palo Alto, CA) allows fast delivery of stereotactic radiotherapy for Stage I lung tumors. We investigated discrepancies between the calculated and delivered dose distributions, as well as the dosimetric impact of leaf interplay with breathing-induced tumor motion. Methods and Materials: In 20 consecutive patients with Stage I lung cancer who completed RapidArc delivery, 15 had tumor motion exceeding 5 mm on four-dimensional computed tomography scan. Static and dynamic measurements were performed with Gafchromic EBT film (International Specialty Products Inc., Wayne, NJ) in a Quasar motion phantom (Modus Medical Devices, London, Ontario, Canada). Static measurements were compared with calculated dose distributions, and dynamic measurements were compared with the convolution of static measurements with sinusoidal motion patterns. Besides clinical treatment plans, additional cases were optimized to create excessive multileaf collimator modulation and delivered on the phantom with peak-to-peak motions of up to 25 mm. {gamma} Analysis with a 3% dose difference and 2- or 1-mm distance to agreement was used to evaluate the accuracy of delivery and the dosimetric impact of the interplay effect. Results: In static mode film dosimetry of the two-arc delivery in the phantom showed that, on average, fewer than 3% of measurements had {gamma} greater than 1. Dynamic measurements of clinical plans showed a high degree of agreement with the convolutions: for double-arc plans, 99.5% met the {gamma} criterion. The degree of agreement was 98.5% for the plans with excessive multileaf collimator modulations and 25 mm of motion. Conclusions: Film dosimetry shows that RapidArc accurately delivers the calculated dose distribution and that interplay between leaves and tumor motion is not significant for single-fraction treatments when RapidArc is delivered with two different arcs.

Ong, Chin Loon, E-mail: c.ong@vumc.n [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Verbakel, Wilko F.A.R.; Cuijpers, Johan P.; Slotman, Ben J.; Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)

2011-01-01

18

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

SciTech Connect

Purpose: 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.Methods: 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.Results: 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).Conclusions: A real-time radiation delivery verification system for dynamic IMRT has been demonstrated that is designed to prevent major mistreatments in modern radiation therapy.

Fuangrod, Todsaporn [Faculty of Engineering and Built Environment, School of Electrical Engineering and Computer Science, the University of Newcastle, NSW 2308 (Australia)] [Faculty of Engineering and Built Environment, School of Electrical Engineering and Computer Science, the University of Newcastle, NSW 2308 (Australia); Woodruff, Henry C.; O’Connor, Daryl J. [Faculty of Science and IT, School of Mathematical and Physical Sciences, the University of Newcastle, NSW 2308 (Australia)] [Faculty of Science and IT, School of Mathematical and Physical Sciences, the University of Newcastle, NSW 2308 (Australia); Uytven, Eric van; McCurdy, Boyd M. C. [Division of Medical Physics, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9 (Canada) [Division of Medical Physics, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9 (Canada); Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba R3T 2N2 (Canada); Department of Radiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2 (Canada); Kuncic, Zdenka [School of Physics, University of Sydney, Sydney, NSW 2006 (Australia)] [School of Physics, University of Sydney, Sydney, NSW 2006 (Australia); Greer, Peter B. [Faculty of Science and IT, School of Mathematical and Physical Sciences, the University of Newcastle, NSW 2308, Australia and Department of Radiation Oncology, Calvary Mater Newcastle Hospital, Locked Bag 7, Hunter region Mail Centre, Newcastle, NSW 2310 (Australia)] [Faculty of Science and IT, School of Mathematical and Physical Sciences, the University of Newcastle, NSW 2308, Australia and Department of Radiation Oncology, Calvary Mater Newcastle Hospital, Locked Bag 7, Hunter region Mail Centre, Newcastle, NSW 2310 (Australia)

2013-09-15

19

Respiration-correlated treatment delivery using feedback-guided breath hold: A technical study  

SciTech Connect

Respiratory motion causes movement of internal structures in the thorax and abdomen, making accurate delivery of radiation therapy to tumors in those areas a challenge. To reduce the uncertainties caused by this motion, we have developed feedback-guided breath hold (FGBH), a novel delivery technique in which radiation is delivered only during a voluntary breath hold that is sustained for as long as the patient feels comfortable. Here we present the technical aspects of FGBH, which involve (1) fabricating the hardware so the respiratory trace can be displayed to the patient, (2) assembling a delay box to be used as a breath-hold detector, and (3) performing quality control tests to ensure that FGBH can be delivered accurately and safely. A commercial respiratory tracking system that uses an external fiducial to monitor abdominal wall motion generates and displays the breathing trace and specific positions in the breathing cycle where a breath hold needs to occur. Hardware was developed to present this display to the patient in the treatment position. Patients view the presentation either on a liquid crystal display or through a pair of virtual reality goggles. Using the respiratory trace as a visual aid, the patient performs a breath hold so that the position representing the location of a fiducial is held within a specified gating window. A delay box was fabricated to differentiate between gating signals received during free breathing and those received during breath hold, allowing radiation delivery only when the fiducial was within the breath-hold gating window. A quality control analysis of the gating delay box and the integrated system was performed to ensure that all of the hardware and components were ready for clinical use.

Nelson, Christopher; Starkschall, George; Balter, Peter; Fitzpatrick, Mathew J.; Antolak, John A.; Tolani, Naresh; Prado, Karl [Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030 (United States)

2005-01-01

20

Simulation of gentamicin delivery for the local treatment of osteomyelitis.  

PubMed

In order to understand the effect of antibiotics delivery to bone tissue, by biodegradable polymeric drug disc, for the treatment of osteomyelitis, a three-dimensional simulation model is developed. The simulation investigates the effect of pressure-induced convection on drug distribution, by taking into account the pressure gradient that exists between capillaries and interstitial space, and also as a result of the surgical opening. The clotting process at the surgical opening is incorporated into the simulation, and the effect of clotting duration is investigated. The clotting duration for the baseline simulation is 2 days and it is observed that increasing this duration depresses the mean drug concentration in the marrow and cortical bone. The effect of double burst release profile is also studied and it is observed that drug concentration drops too rapidly after the first burst to provide any therapeutic effect. However, it is shown that the drug concentration after the second burst stays above the minimum inhibitory concentration of the bacteria for a longer period of time, than would have been observed for a mono-burst release. Inserting non-biodegradable polymethylmethacrylate (PMMA) beads into bone seems to cause a higher average concentration of drug in the marrow. However, this could be brought about by the difference in the geometry between the disc and the bead, and the amount of drug packed in each bead. Further simulations on the management of dead space shows the ineffectiveness of having the void filled up with surgical gel as it becomes an additional barrier to drug delivery to the infected tissues. PMID:15981276

Lee, Chian Guan; Fu, Yin-Chih; Wang, Chi-Hwa

2005-09-01

21

Functional polymers of gene delivery for treatment of myocardial infarct.  

PubMed

Ischemic heart disease is rapidly growing as the common cause of death in the world. It is a disease that occurs as a result of coronary artery stenosis and is caused by the lack of oxygen within cardiac muscles due to an imbalance between oxygen supply and demand. The conventional medical therapy is focused on the use of drug eluting stents, coronary-artery bypass graft surgery and anti-thrombosis. Gene therapy provides great opportunities for treatment of cardiovascular disease. In order for gene therapy to be successful, the development of proper gene delivery systems and hypoxia-regulated gene expression vectors is the most important factors. Several non-viral gene transfer methods have been developed to overcome the safety problems of viral transduction. Some of which include plasmids that regulate gene expression that is controlled by environment specific promoters in the transcriptional or the translational level. This review explores polymeric gene carriers that target the myocardium and hypoxia-inducible vectors, which regulate gene expression in response to hypoxia, and their application in animal myocardial infarction models. PMID:25076177

Won, Young-Wook; Bull, David A; Kim, Sung Wan

2014-12-10

22

Iontophoretic drug delivery for the treatment of scars.  

PubMed

Topical treatment of hypertrophic scars is challenging because of poor penetrability of drugs into the scar tissue. The objective of the study was to investigate the effectiveness of iontophoresis to deliver medicaments across the scar epidermis. Initially, biophysical studies were performed to investigate the differences between scar and normal skin epidermis obtained from cadaver. In case of scar skin epidermis, the transepidermal water loss was not significantly different from the normal skin epidermis, whereas the electrical resistivity was significantly higher. The passive permeation flux of sodium fluorescein was approximately one-third of that across the normal skin epidermis. Scanning electron microscopy studies revealed that the two membranes were alike except that the scar skin epidermis lacked follicles. Cathodal iontophoresis enhanced the delivery of sodium fluorescein across the scar skin epidermis by approximately 46 folds [51.90 ± 8.82 ng/(cm(2) h)]. However, the transport of sodium fluorescein across the scar skin epidermis was about an order of magnitude less than the normal skin epidermis. Overall, the studies suggest that iontophoresis could be utilized to overcome the barrier resistance of scar skin epidermis and treat the scar regionally. PMID:24648369

Manda, Prashanth; Angamuthu, Muralikrishnan; Hiremath, Shobharani R; Raman, Vijayasankar; Murthy, S Narasimha

2014-06-01

23

Microcapsule drug delivery device for treatment of glioblastoma multiforme  

E-print Network

Controlled-release drug delivery systems are capable of treating debilitating diseases, including cancer. Brain cancer, in particular glioblastoma multiforme (GBM), is an extremely invasive cancer with a dismal prognosis. ...

Scott, Alexander Wesley

2010-01-01

24

Sustained-Release Delivery Systems for Treatment of Dental Diseases  

Microsoft Academic Search

Sustained-release delivery systems allow the effective targeting of drugs for treating dental and periodontal diseases. Since dental diseases are chronic, the therapeutic agents used should persist in the oral cavity for as long as possible. Implanting fluoride, chlorhexidine, and other antiseptic agents embedded into sustained-release polymeric matrices into the oral cavity prevents cariogenic plaque accumulation. Both fibers and slab-like sustained-delivery

Michael Friedman; Doron Steinberg

1990-01-01

25

Ultrasonic-Activated Micellar Drug Delivery for Cancer Treatment  

PubMed Central

The use of nanoparticles and ultrasound in medicine continues to evolve. Great strides have been made in the areas of producing micelles, nanoemulsions and solid nanoparticles that can be used in drug delivery. An effective nanocarrier allows for the delivery of a high concentration of potent medications to targeted tissue while minimizing the side effect of the agent to the rest of the body. Polymeric micelles have been shown to encapsulate therapeutic agents and maintain their structural integrity at lower concentrations. Ultrasound is currently being used in drug delivery as well as diagnostics, and has many advantages that elevate its importance in drug delivery. The technique is non-invasive, thus no surgery is needed; the ultrasonic waves can be easily controlled by advanced electronic technology so that they can be focused on the desired target volume. Additionally, the physics of ultrasound are widely used and well understood; thus ultrasonic application can be tailored towards a particular drug delivery system. In this article, we review the recent progress made in research that utilizes both polymeric micelles and ultrasonic power in drug delivery. PMID:18506804

Husseini, Ghaleb A.; Pitt, William G.

2008-01-01

26

Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?  

SciTech Connect

Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio Registered-Sign treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy.

Wong, Sharon [National University of Singapore, Yong Loo Lin School of Medicine (Singapore); Back, Michael [Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales (Australia); Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun [National University, Cancer Institute, Department of Radiation Oncology, National University, Hospital, Tower Block (Singapore); Lu, Jaide Jay, E-mail: mdcljj@nus.edu.sg [National University of Singapore, Yong Loo Lin School of Medicine (Singapore); National University, Cancer Institute, Department of Radiation Oncology, National University, Hospital, Tower Block (Singapore)

2012-07-01

27

A Monte Carlo tool for evaluating VMAT and DIMRT treatment deliveries including planar detectors  

NASA Astrophysics Data System (ADS)

The aim of this work is to describe and validate a new general research tool that performs Monte Carlo (MC) simulations for volumetric modulated arc therapy (VMAT) and dynamic intensity modulated radiation therapy (DIMRT), simultaneously tracking dose deposition in both the patient CT geometry and an arbitrary planar detector system. The tool is generalized to handle either entrance or exit detectors and provides the simulated dose for the individual control-points of the time-dependent VMAT and DIMRT deliveries. The MC simulation tool was developed with the EGSnrc radiation transport. For the individual control point simulation, we rotate the patient/phantom volume only (i.e. independent of the gantry and planar detector geometries) using the gantry angle in the treatment planning system (TPS) DICOM RP file such that each control point has its own unique phantom file. After MC simulation, we obtained the total dose to the phantom by summing dose contributions for all control points. Scored dose to the sensitive layer of the planar detector is available for each control point. To validate the tool, three clinical treatment plans were used including VMAT plans for a prostate case and a head-and-neck case, and a DIMRT plan for a head-and-neck case. An electronic portal imaging device operated in ‘movie’ mode was used with the VMAT plans delivered to cylindrical and anthropomorphic phantoms to validate the code using an exit detector. The DIMRT plan was delivered to a novel transmission detector, to validate the code using an entrance detector. The total MC 3D absolute doses in patient/phantom were compared with the TPS doses, while 2D MC doses were compared with planar detector doses for all individual control points, using the gamma evaluation test with 3%/3 mm criteria. The MC 3D absolute doses demonstrated excellent agreement with the TPS doses for all the tested plans, with about 95% of voxels having ? <1 for the plans. For planar dosimetry image comparisons, we defined an acceptable pass rate of >90% of percentage pixels with ? <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system.

Asuni, G.; van Beek, T. A.; Venkataraman, S.; Popescu, I. A.; McCurdy, B. M. C.

2013-06-01

28

The impact of treatment density and molecular weight for fractional laser-assisted drug delivery.  

PubMed

Ablative fractional lasers (AFXL) facilitate uptake of topically applied drugs by creating narrow open micro-channels into the skin, but there is limited information on optimal laser settings for delivery of specific molecules. The objective of this study was to investigate the impact of laser treatment density (% of skin occupied by channels) and molecular weight (MW) for fractional CO(2) laser-assisted drug delivery. AFXL substantially increased intra- and transcutaneous delivery of polyethylene glycols (PEGs) in a MW range from 240 to 4300 Da (Nuclear Magnetic Resonance, p<0.01). Increasing laser density from 1 to 20% resulted in augmented intra- and transdermal delivery (p<0.01), but densities higher than 1% resulted in reduced delivery per channel. Mass spectrometry indicated that larger molecules have greater intracutaneous retention than transcutaneous penetration. At 5% density, median delivery of PEGs with mean MW of 400, 1000, 2050 and 3350 Da were respectively 0.87, 0.31, 0.23 and 0.15 mg intracutaneously and 0.72, 0.20. 0.08 and 0.03 mg transcutaneously, giving a 5.8- and 24.0-fold higher intra- and transcutaneous delivery of PEG400 than PEG3350 (p<0.01). This study substantiates that fractional CO(2) laser treatment allows uptake of small and large molecules into and through human skin, and that laser density can be varied to optimize intracutaneous or transcutaneous delivery. PMID:23000695

Haak, Christina S; Bhayana, Brijesh; Farinelli, William A; Anderson, R Rox; Haedersdal, Merete

2012-11-10

29

Results of a UK survey on methods for compensating for unscheduled treatment interruptions and errors in treatment delivery  

Microsoft Academic Search

In order to obtain a preliminary overview of the current national status regarding the management of both unintentional interruptions to radiotherapy treatments and inadvertent errors in treatment delivery, a short questionnaire was sent to 60 UK radiotherapy departments, of which 35 (58%) responded. The study was initiated by the authors and was not commissioned by any professional body. Amongst the

R G Dale; B Jones; J A Sinclair; C Comins; E Antoniou

2007-01-01

30

Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge  

PubMed Central

Delivery of medications to the inner ear has been an area of considerable growth in both the research and clinical realms over the past several decades. Systemic delivery of medication destined for treatment of the inner ear is the foundation upon which newer delivery techniques have been developed. Due to systemic side effects, investigators and clinicians have begun developing and utilizing techniques to deliver therapeutic agents locally. Alongside the now commonplace use of intratympanic gentamicin for Meniere's disease and the emerging use of intratympanic steroids for sudden sensorineural hearing loss, novel technologies, such as hydrogels and nanoparticles, are being explored. At the horizon of inner ear drug delivery techniques, intracochlear devices that leverage recent advances in microsystems technology are being developed to apply medications directly into the inner ear. Potential uses for such devices include neurotrophic factor and steroid delivery with cochlear implantation, RNA interference technologies, and stem cell therapy. The historical, current, and future delivery techniques and uses of drug delivery for treatment of inner ear disease serve as the basis for this review. PMID:19952751

McCall, Andrew A.; Leary Swan, Erin E.; Borenstein, Jeffrey T.; Sewell, William F.; Kujawa, Sharon G.; McKenna, Michael J.

2009-01-01

31

Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases  

PubMed Central

Human skin not only functions as a permeation barrier (mainly due to the stratum corneum layer), but also provides a unique delivery pathway for therapeutic and other active agents. These compounds penetrate via intercellular, intracellular and transappendageal routes, resulting in topical delivery (into skin strata) and transdermal delivery (to subcutaneous tissues and into the systemic circulation). Passive and active permeation enhancement methods have been widely applied to increase the cutaneous penetration. The pathology, pathogenesis and topical treatment approaches of dermatological diseases, such as psoriasis, contact dermatitis, and skin cancer, are then discussed. Recent literature has demonstrated that nanoparticles-based topical delivery systems can be successful in treating these skin conditions. The studies are reviewed starting with the nanoparticles based on natural polymers specially chitosan, followed by those made of synthetic, degradable (aliphatic polyesters) and non-degradable (polyarylates) polymers; emphasis is given to nanospheres made of polymers derived from naturally occurring metabolites, the tyrosine-derived nanospheres (TyroSpheres™). In summary, the nanoparticles-based topical delivery systems combine the advantages of both the nano-sized drug carriers and the topical approach, and are promising for the treatment of skin diseases. For the perspectives, the penetration of ultra-small nanoparticles (size smaller than 40 nm) into skin strata, the targeted delivery of the encapsulated drugs to hair follicle stem cells, and the combination of nanoparticles and microneedle array technologies for special applications such as vaccine delivery are discussed. PMID:23386536

Zhang, Zheng; Tsai, Pei-Chin; Ramezanli, Tannaz; Michniak-Kohn, Bozena B.

2013-01-01

32

Microparticulate drug delivery systems as an adjunct to cancer treatment.  

PubMed

In an attempt to improve the therapeutic ratio of cytotoxic drugs, which have steep dose-response curves, microparticulate drug delivery systems (MDDS) have been designed for regional administration. Introduction of antineoplastic drug containing microspheres, of appropriate size, into the arterial system of an organ harboring primary or metastatic tumor, will cause tumor infarction by an embolic effect and provide a slow release source of drug trapped within the tumor microvasculature. This review describes recent innovations in synthesis of MDDS and their potential clinical application. PMID:3300944

Kerr, D J

1987-01-01

33

Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy  

SciTech Connect

Purpose: To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. Methods: The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. Results: The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 {+-} 35 patients. Conclusions: This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.

Suzuki, Kazumichi; Gillin, Michael T.; Sahoo, Narayan; Zhu, X. Ronald; Lee, Andrew K.; Lippy, Denise [Departments of Radiation Physics and Radiation Oncology, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); The Proton Therapy Center Houston, Ltd., L.L.P., 1840 Old Spanish Trail, Houston, Texas 77054 (United States)

2011-07-15

34

Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.  

PubMed

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. PMID:23624358

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-12-10

35

Recent Advances in Delivery of Drug-Nucleic Acid Combinations for Cancer Treatment  

PubMed Central

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. PMID:23624358

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-01-01

36

Breathing-Synchronized Delivery: A Potential Four-Dimensional Tomotherapy Treatment Technique  

SciTech Connect

Purpose: To introduce a four-dimensional (4D) tomotherapy treatment technique with improved motion control and patient tolerance. Methods and Materials: Computed tomographic images at 10 breathing phases were acquired for treatment planning. The full exhalation phase was chosen as the planning phase, and the CT images at this phase were used as treatment-planning images. Region of interest delineation was the same as in traditional treatment planning, except that no breathing motion margin was used in clinical target volume-planning target volume expansion. The correlation between delivery and breathing phases was set assuming a constant gantry speed and a fixed breathing period. Deformable image registration yielded the deformation fields at each phase relative to the planning phase. With the delivery/breathing phase correlation and voxel displacements at each breathing phase, a 4D tomotherapy plan was obtained by incorporating the motion into inverse treatment plan optimization. A combined laser/spirometer breathing tracking system has been developed to monitor patient breathing. This system is able to produce stable and reproducible breathing signals representing tidal volume. Results: We compared the 4D tomotherapy treatment planning method with conventional tomotherapy on a static target. The results showed that 4D tomotherapy can achieve dose distributions on a moving target similar to those obtained with conventional delivery on a stationary target. Regular breathing motion is fully compensated by motion-incorporated breathing-synchronized delivery planning. Four-dimensional tomotherapy also has close to 100% duty cycle and does not prolong treatment time. Conclusion: Breathing-synchronized delivery is a feasible 4D tomotherapy treatment technique with improved motion control and patient tolerance.

Zhang Tiezhi [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)]. E-mail: tiezhi.zhang@beaumont.edu; Lu Weiguo [TomoTherapy Inc., Madison, WI (United States); Olivera, Gustavo H. [TomoTherapy Inc., Madison, WI (United States); Keller, Harry [Department of Radiation Physics, Princess Margaret Hospital, Toronto, Ontario (Canada); Jeraj, Robert [Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Manon, Rafael [Department of Radiation Oncology, M.D. Anderson Cancer Center, Orlando, FL (United States); Mehta, Minesh [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Mackie, Thomas R. [TomoTherapy Inc., Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Paliwal, Bhudatt [Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Department of Human Oncology, University of Wisconsin, Madison, WI (United States)

2007-08-01

37

Delivery.  

PubMed

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

Miller, Thomas A

2013-11-01

38

Delivery  

PubMed Central

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

Miller, Thomas A

2013-01-01

39

Nanostructured Platforms for the Sustained and Local Delivery of Antibiotics in the Treatment of Osteomyelitis  

PubMed Central

This article provides a critical view of the current state of the development of nanoparticulate and other solid-state carriers for the local delivery of antibiotics in the treatment of osteomyelitis. Mentioned are the downsides of traditional means for treating bone infection, which involve systemic administration of antibiotics and surgical debridement, along with the rather imperfect local delivery options currently available in the clinic. Envisaged are more sophisticated carriers for the local and sustained delivery of antimicrobials, including bioresorbable polymeric, collagenous, liquid crystalline, and bioglass- and nanotube-based carriers, as well as those composed of calcium phosphate, the mineral component of bone and teeth. A special emphasis is placed on composite multifunctional antibiotic carriers of a nanoparticulate nature and on their ability to induce osteogenesis of hard tissues demineralized due to disease. An ideal carrier of this type would prevent the long-term, repetitive, and systemic administration of antibiotics and either minimize or completely eliminate the need for surgical debridement of necrotic tissue. Potential problems faced by even hypothetically “perfect” antibiotic delivery vehicles are mentioned too, including (i) intracellular bacterial colonies involved in recurrent, chronic osteomyelitis; (ii) the need for mechanical and release properties to be adjusted to the area of surgical placement; (iii) different environments in which in vitro and in vivo testings are carried out; (iv) unpredictable synergies between drug delivery system components; and (v) experimental sensitivity issues entailing the increasing subtlety of the design of nanoplatforms for the controlled delivery of therapeutics. PMID:25746204

Uskokovi?, Vuk

2015-01-01

40

Evaluation of domperidone dosages and delivery methods for the treatment of fescue toxicosis in beef heifers  

Technology Transfer Automated Retrieval System (TEKTRAN)

The objective of this study was to develop a practical method of domperidone delivery to ameliorate the symptoms of fescue toxicosis in beef heifers. Experiment 1 used 42 crossbred heifers assigned to 1 of 7 treatment groups (n = 6/trt); positive control (0.44 mg domperidone/kg BW daily s.c.), nega...

41

Food Processing by Pulsed Electric Fields: Treatment Delivery, Inactivation Level, and Regulatory Aspects  

Microsoft Academic Search

Industrial implementation of pulsed electric field electro-technology (PEF) for food preservation has been rather slow, despite its potential to produce safe, nutritious and high-quality products. Several research groups around the world are in a race to validate and optimize the operation of PEF systems. Insufficient kinetic studies and inaccurate treatment delivery assessment are some of the main obstacles to the

M. M. Góngora-Nieto; D. R. Sepúlveda; P. Pedrow; G. V. Barbosa-Cánovas; B. G. Swanson

2002-01-01

42

Accurate calculation of core-electron binding energies: Multireference perturbation treatment  

NASA Astrophysics Data System (ADS)

Multireference perturbation theory (MRPT) with multiconfigurational self-consistent field (MCSCF) reference functions is applied to the calculations of core-electron binding energies (CEBEs) of atoms and molecules. Orbital relaxations in a core-ionized state and electron correlation are both taken into account in a conventional MCSCF-MRPT procedure. In the MCSCF calculation, the target core ionized state is directly optimized as an excited state and this treatment can completely prevent a variational collapse. Multireference Møller-Plesset perturbation theory and multiconfigurational self-consistent field reference quasidegenerated perturbation theory were used to treat electron correlation. The present method quite accurately reproduced the 1s CEBEs of CH4, NH3, H2O, and FH; the average deviation from the experimental data is 0.11 eV using Ahlrichs' VTZ basis set. The C 1s and O 1s CEBEs of formic acid and acetic acid were calculated and the results are consistent with the bonding characters of the atoms in these molecules. The present procedure can also be applied to CEBEs of higher angular momentum orbitals by including spin-orbit coupling. The calculated CEBEs of Ar 2p, HCl 2p, Kr 3d, and HBr 3d are in reasonable agreement with the available experimental values. In the calculation of the 3d CEBEs, a relativistic correction significantly improves the agreements. The effect of polarization functions is also discussed.

Shirai, Soichi; Yamamoto, Satoru; Hyodo, Shi-aki

2004-10-01

43

Volumetric-modulated arc therapy with RapidArc®: An evaluation of treatment delivery efficiency  

PubMed Central

Aim/background To evaluate how the use of volumetric-modulated arc therapy (VMAT) with RapidArc® can improve treatment delivery efficiency based on the analysis of the beam-on times and monitor units (MU) needed to deliver therapy for multiple clinical applications in a large patient population. Materials and methods A total of 898 treatment courses were delivered in 745 patients treated from October 2008 to March 2013 using RapidArc® treatment plans generated in Eclipse™ TPS. All patients were treated with curative or palliative intent using different techniques including conventional fractionation (83%) and radiosurgery or SBRT (17%), depending on the clinical indications. Treatment delivery was evaluated based on measured beam-on time and recorded MU values delivered on a Varian Trilogy™ linear accelerator. Results For conventional fractionation treatments using RapidArc®, the delivery times ranged from 38 s to 4 min and 40 s (average 2 min and 6 s). For radiosurgical treatments the delivery times ranged from 1 min and 42 s to 9 min and 22 s (average 4 min and 4 s). The average number of MU per Gy was 301 for the entire group, with 285 for the conventional group and 317 for the radiosurgical group. Conclusions In this study with a large heterogeneous population, treatments using RapidArc® were delivered with substantially less beam-on time and fewer MUs than conventional fractionation. This was highly advantageous, increasing flexibility of the scheduling allowing treatment of radiosurgery patients during the regular daily work schedule. Additionally, reduction of leakage radiation dose was achieved. PMID:24416583

Amendola, Beatriz E.; Amendola, Marco; Perez, Naipy; Iglesias, Alejandro; Wu, Xiaodong

2013-01-01

44

Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging  

PubMed Central

The aging process causes a number of changes in the skin, including oxidative stress and dyschromia. The kojic acid (KA) is iron chelator employed in treatment of skin aging, and inhibits tyrosinase, promotes depigmentation. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation through the skin and improve the drug activity. This study is aimed at structurally developing and characterizing a kojic acid-loaded LCS, consists of water (W), cetostearyl isononanoate (oil—O) and PPG-5-CETETH-20 (surfactant-S) and evaluating its in vitro skin permeation and retention. Three regions of the diagram were selected for characterization: A (35% O, 50% S, 15% W), B (30% O, 50% S, 20% W) and C (20% O, 50% S, 30% W), to which 2% KA was added. The formulations were subjected to polarized light microscopy, which indicated the presence of a hexagonal mesophase. Texture and bioadhesion assay showed that formulation B is suitable for topical application. According to the results from the in vitro permeation and retention of KA, the formulations developed can modulate the permeation of KA in the skin. The in vitro cytotoxic assays showed that KA-unloaded LCS and KA-loaded LCS didn't present cytotoxicity. PPG-5-CETETH-20-based systems may be a promising platform for KA skin delivery. PMID:24369010

Gonçalez, M. L.; Corrêa, M. A.; Chorilli, M.

2013-01-01

45

Social Workers and Delivery of Evidence-Based Psychosocial Treatments for Substance Use Disorders  

PubMed Central

Social workers encounter individuals with substance use disorders (SUDs) in a variety of settings. With changes in health care policy and a movement toward integration of health and behavioral health services, social workers will play an increased role vis-a-vis SUD. As direct service providers, administrators, care managers and policy makers, they will select, deliver, or advocate for delivery of evidence-based SUD treatment practices. This paper provides an overview of effective psychosocial SUD treatment approaches. In addition to describing the treatments, the article discusses empirical support, populations for whom the treatments are known to be efficacious, and implementation issues. PMID:23731420

WELLS, ELIZABETH A.; KRISTMAN-VALENTE, ALLISON N.; PEAVY, K. MICHELLE; JACKSON, T. RON

2013-01-01

46

Improved delivery of magnetic nanoparticles with chemotherapy cancer treatment  

NASA Astrophysics Data System (ADS)

Most nanoparticle-based cancer therapeutic strategies seek to develop an effective individual cancer cell or metastatic tumor treatment. Critical to the success of these therapies is to direct as much of the agent as possible to the targeted tissue while avoiding unacceptable normal tissue complications. In this light, three different cisplatinum/magnetic nanoparticle (mNP) administration regimens were investigated. The most important finding suggests that clinically relevant doses of cisplatinum result in a significant increase in the tumor uptake of systemically delivered mNP. This enhancement of mNP tumor uptake creates the potential for an even greater therapeutic ratio through the addition of mNP based, intracellular hyperthermia.

Petryk, Alicia A.; Giustini, Andrew J.; Gottesman, Rachel E.; Hoopes, P. Jack

2013-02-01

47

Intranasal clobazam delivery in the treatment of status epilepticus.  

PubMed

The aim of the present investigation was to prepare and characterize clobazam mucoadhesive microemulsion (CZMME) to assess brain drug uptake and protection against pentylenetetrazole (PTZ)-induced convulsions in mice. Clobazam microemulsion (CZME) and CZMME were prepared by titration method and characterized. Brain uptake and pharmacokinetic parameters were calculated from drug concentration in mice brain versus time plots following intranasal administration of radiolabeled CZME and CZMME, intravenous and intranasal administration of radiolabeled clobazam solution. Gamma scintigraphy imaging of rabbit brain following intranasal administration was performed. Formulations were investigated for the onset of seizures in PTZ-challenged mice. Brain targeting efficiency and direct nose-to-brain transport percentage for mucoadhesive microemulsion suggested an improved brain uptake following intranasal administration. The findings were supported by gamma scintigraphy images. Delay in onset of PTZ-induced seizures with CZMME compared with positive control and placebo-treated groups confirmed the improved brain uptake. However, extensive animal studies followed by clinical trials are necessary to develop a product suitable for emergencies of acute seizures in status epilepticus and patients suffering from drug tolerance and hepatic impairment on long-term use in treatment of epilepsy, schizophrenia, and anxiety. PMID:20799366

Florence, Kiruba; Manisha, Lalan; Kumar, Babbar Anil; Ankur, Kaul; Kumar, Mishra Anil; Ambikanandan, Misra

2011-02-01

48

Cervical cancer treatment with a locally insertable controlled release delivery system  

PubMed Central

Local delivery of cancer chemotherapeutics enables sustained drug levels at the site of action thereby reducing systemic side effects. A novel insertable polymeric drug delivery system for cervical cancer treatment is presented. Cisplatin, the first line of therapy employed for cervical cancers, was incorporated in a poly(ethylene-co-vinyl acetate) (EVAc) device that is similar to those currently used for vaginal contraceptive delivery. Cisplatin crystals were uniformly dispersed in the polymeric system without undergoing significant dissolution in the polymer matrix. Cisplatin dissolution from the devices was biphasic, consistent with a matrix-type controlled-release system with an initial rapid release phase followed by a slower, linear release phase. Depending on the drug loading in the polymeric devices, the near-linear release phase varied in rate according both empirical, linear curve-fitting (0.38±0.15 ?g/day to 46.9±10.0 ?g/day) and diffusion analysis based upon diffusion through a porous structure (Dapp from 1.3±0.5×10?9 cm2/s to 5.8±0.3×10?12 cm2/s). The devices were tested for in vitro activity and found to be effective against both HPV positive and HPV negative cervical cancer cell lines. Preliminary studies indicate that this delivery system would be a good candidate for investigation as a choice of treatment in cervical cancers. PMID:17034891

Keskar, Vandana; Mohanty, Prem S.; Gemeinhart, Ernest J.; Gemeinhart, Richard A.

2006-01-01

49

Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery  

PubMed Central

Tuberculosis (TB) causes almost 2 million deaths annually, and an increasing number of patients are resistant to existing therapies. Patients who have TB require lengthy chemotherapy, possibly because of poor penetration of antibiotics into granulomas where the bacilli reside. Granulomas are morphologically similar to solid cancerous tumors in that they contain hypoxic microenvironments and can be highly fibrotic. Here, we show that TB-infected rabbits have impaired small molecule distribution into these disease sites due to a functionally abnormal vasculature, with a low-molecular-weight tracer accumulating only in peripheral regions of granulomatous lesions. Granuloma-associated vessels are morphologically and spatially heterogeneous, with poor vessel pericyte coverage in both human and experimental rabbit TB granulomas. Moreover, we found enhanced VEGF expression in both species. In tumors, antiangiogenic, specifically anti-VEGF, treatments can “normalize” their vasculature, reducing hypoxia and creating a window of opportunity for concurrent chemotherapy; thus, we investigated vessel normalization in rabbit TB granulomas. Treatment of TB-infected rabbits with the anti-VEGF antibody bevacizumab significantly decreased the total number of vessels while normalizing those vessels that remained. As a result, hypoxic fractions of these granulomas were reduced and small molecule tracer delivery was increased. These findings demonstrate that bevacizumab treatment promotes vascular normalization, improves small molecule delivery, and decreases hypoxia in TB granulomas, thereby providing a potential avenue to improve delivery and efficacy of current treatment regimens. PMID:25624495

Datta, Meenal; Via, Laura E.; Kamoun, Walid S.; Liu, Chong; Chen, Wei; Seano, Giorgio; Weiner, Danielle M.; Schimel, Daniel; England, Kathleen; Gao, Xing; Xu, Lei; Barry, Clifton E.; Jain, Rakesh K.

2015-01-01

50

Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy  

NASA Astrophysics Data System (ADS)

Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing, beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

Sengbusch, Evan R.

51

Nanotechnology-based drug delivery systems for treatment of oral cancer: a review  

PubMed Central

Oral cancer (oral cavity and oropharynx) is a common and aggressive cancer that invades local tissue, can cause metastasis, and has a high mortality rate. Conventional treatment strategies, such as surgery and chemoradiotherapy, have improved over the past few decades; however, they remain far from optimal. Currently, cancer research is focused on improving cancer diagnosis and treatment methods (oral cavity and oropharynx) nanotechnology, which involves the design, characterization, production, and application of nanoscale drug delivery systems. In medicine, nanotechnologies, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, hydrogels, cyclodextrin complexes, and liquid crystals, are promising tools for diagnostic probes and therapeutic devices. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for oral cancers. PMID:25143724

Calixto, Giovana; Bernegossi, Jéssica; Fonseca-Santos, Bruno; Chorilli, Marlus

2014-01-01

52

Intravaginal clindamycin treatment for bacterial vaginosis: Effects on preterm delivery and low birth weight  

Microsoft Academic Search

OBJECTIVE: Our goal was to evaluate whether treatment of bacterial vaginosis during pregnancy with 2% clindamycin vaginal cream reduces the incidence of either preterm delivery or low birth weight or of both.STUDY DESIGN: A multicenter, double-blind, randomized, placebo-controlled trial in Indonesia compared a 2% clindamycin vaginal cream with a placebo cream. Women seeking prenatal care at 14 to 26 weeks

M. R. Joesoef; S. L. Hillier; G. Wiknjosastro; H. Sumapouw; M. Linnan; W. Norojono; A. Idajadi; B. Utomo

1995-01-01

53

Nanoparticle-Mediated Systemic Delivery of siRNA for Treatment of Cancers and Viral Infections  

PubMed Central

RNA interference (RNAi) is an endogenous post-transcriptional gene regulatory mechanism, where non-coding, double-stranded RNA molecules interfere with the expression of certain genes in order to silence it. Since its discovery, this phenomenon has evolved as powerful technology to diagnose and treat diseases at cellular and molecular levels. With a lot of attention, short interfering RNA (siRNA) therapeutics has brought a great hope for treatment of various undruggable diseases, including genetic diseases, cancer, and resistant viral infections. However, the challenge of their systemic delivery and on how they are integrated to exhibit the desired properties and functions remains a key bottleneck for realizing its full potential. Nanoparticles are currently well known to exhibit a number of unique properties that could be strategically tailored into new advanced siRNA delivery systems. This review summarizes the various nanoparticulate systems developed so far in the literature for systemic delivery of siRNA, which include silica and silicon-based nanoparticles, metal and metal oxides nanoparticles, carbon nanotubes, graphene, dendrimers, polymers, cyclodextrins, lipids, hydrogels, and semiconductor nanocrystals. Challenges and barriers to the delivery of siRNA and the role of different nanoparticles to surmount these challenges are also included in the review. PMID:25057313

Draz, Mohamed Shehata; Fang, Binbin Amanda; Zhang, Pengfei; Hu, Zhi; Gu, Shenda; Weng, Kevin C.; Gray, Joe W.; Chen, Fanqing Frank

2014-01-01

54

A Bayesian approach to real-time 3D tumor localization via monoscopic x-ray imaging during treatment delivery  

SciTech Connect

Purpose: Monoscopic x-ray imaging with on-board kV devices is an attractive approach for real-time image guidance in modern radiation therapy such as VMAT or IMRT, but it falls short in providing reliable information along the direction of imaging x-ray. By effectively taking consideration of projection data at prior times and/or angles through a Bayesian formalism, the authors develop an algorithm for real-time and full 3D tumor localization with a single x-ray imager during treatment delivery. Methods: First, a prior probability density function is constructed using the 2D tumor locations on the projection images acquired during patient setup. Whenever an x-ray image is acquired during the treatment delivery, the corresponding 2D tumor location on the imager is used to update the likelihood function. The unresolved third dimension is obtained by maximizing the posterior probability distribution. The algorithm can also be used in a retrospective fashion when all the projection images during the treatment delivery are used for 3D localization purposes. The algorithm does not involve complex optimization of any model parameter and therefore can be used in a ''plug-and-play'' fashion. The authors validated the algorithm using (1) simulated 3D linear and elliptic motion and (2) 3D tumor motion trajectories of a lung and a pancreas patient reproduced by a physical phantom. Continuous kV images were acquired over a full gantry rotation with the Varian TrueBeam on-board imaging system. Three scenarios were considered: fluoroscopic setup, cone beam CT setup, and retrospective analysis. Results: For the simulation study, the RMS 3D localization error is 1.2 and 2.4 mm for the linear and elliptic motions, respectively. For the phantom experiments, the 3D localization error is < 1 mm on average and < 1.5 mm at 95th percentile in the lung and pancreas cases for all three scenarios. The difference in 3D localization error for different scenarios is small and is not statistically significant. Conclusions: The proposed algorithm eliminates the need for any population based model parameters in monoscopic image guided radiotherapy and allows accurate and real-time 3D tumor localization on current standard LINACs with a single x-ray imager.

Li, Ruijiang; Fahimian, Benjamin P.; Xing, Lei [Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States)

2011-07-15

55

Convection-enhanced delivery of camptothecin-loaded polymer nanoparticles for treatment of intracranial tumors  

PubMed Central

Direct delivery of chemotherapy agents to the brain via degradable polymer delivery systems—such as Gliadel®—is a clinically proven method for treatment of glioblastoma multiforme, but there are important limitations with the current technology—including the requirement for surgery, profound local tissue toxicity, and limitations in diffusional penetration of agents—that limit its application and effectiveness. Here, we demonstrate another technique for direct, controlled delivery of chemotherapy to the brain that provides therapeutic benefit with fewer limitations. In our new approach, camptothecin (CPT)-loaded poly(lacticco-glycolic acid) (PLGA) nanoparticles are infused via convection-enhanced delivery (CED) to a stereotactically defined location in the brain, allowing simultaneous control of location, spread, and duration of drug release. To test this approach, CPT-PLGA nanoparticles (~100 nm in diameter) were synthesized with 25% drug loading. When these nanoparticles were incubated in culture with 9L gliosarcoma cells, the IC50 of CPT-PLGA nanoparticles was 0.04 µM, compared to 0.3 µM for CPT alone. CPT-PLGA nanoparticles stereotactically delivered by CED improved survival in rats with intracranial 9L tumors: the median survival for rats treated with CPT-PLGA nanoparticles (22 days) was significantly longer than unloaded nanoparticles (15 days) and free CPT infusion (17 days). CPT-PLGA nanoparticle treatment also produced significantly more long-term survivors (30% of animals were free of disease at 60 days) than any other treatment. CPT was present in tissues harvested up to 53 days post-infusion, indicating prolonged residence at the local site of administration. These are the first results to demonstrate the effectiveness of combining polymer-controlled release nanoparticles with CED in treating fatal intracranial tumors. PMID:21691426

Sawyer, Andrew J.; Saucier-Sawyer, Jennifer K.; Booth, Carmen J.; Liu, Jie; Patel, Toral; Piepmeier, Joseph M.

2011-01-01

56

Investigating end-to-end accuracy of image guided radiation treatment delivery using a micro-irradiator  

PubMed Central

Purpose There is significant interest in delivering precisely targeted small-volume radiation treatments, in the pre-clinical setting, to study dose-volume relationships with tumour control and normal tissue damage. For these studies it is vital that image guidance systems and target positioning are accurately aligned (IGRT), in order to deliver dose precisely and accurately according to the treatment plan. In this work we investigate the IGRT targeting accuracy of the X-RAD 225 Cx system from Precision X-Ray using high resolution 3D dosimetry techniques. Method Small cylindrical PRESAGE™ dosimeters were used with optical-CT readout (DMOS) to verify the accuracy of 2.5, 1.0, and 5.0 mm X-RAD cone attachments. The dosimeters were equipped with four target points, visible on both CBCT and optical-CT, at which a 7-field coplanar treatment plan was delivered with the respective cone. Targeting accuracy (distance to agreement between imaging positioning and therapeutic delivery) and cone alignment (isocenter precision under gantry rotation) were measured using the optical-CT images. Results Optical-CT readout of the first 2.5 mm cone dosimeter revealed a significant targeting error of 2.1±0.6 mm and a cone misalignment of 1.3±0.1 mm. After the IGRT hardware and software had been recalibrated, these errors were reduced to 0.5±0.1 mm and 0.18±0.04 mm respectively, within the manufacturer specified 0.5 mm. Results from the 1.0 mm cone were 0.5±0.3 mm targeting accuracy and 0.4±0.1 mm cone misalignment, within the 0.5 mm specification. The results from the 5.0 mm cone were 1.0±0.2 mm targeting accuracy and 0.18±0.06 mm cone misalignment, outside of accuracy specifications. Conclusion Quality assurance of small field IGRT targeting and delivery accuracy is a challenging task. The use of a 3D dosimetry technique, where targets are visible on both CBCT and optical-CT, enabled identification and quantification of a targeting error in 3D. After correction, the targeting accuracy of the irradiator was verified to be within 0.5 mm (or 1.0 mm for the 5.0 mm cone) and the cone alignment was verified to be within 0.2 mm (or 0.4 mm for the 1.0 mm cone). The PRESAGE™/DMOS system proved valuable for end-to-end verification of small field IGRT capabilities. PMID:24140983

Rankine, L J; Newton, J; Bache, S T; Das, S K; Adamovics, J; Kirsch, D G; Oldham, M

2013-01-01

57

Postoperative Irradiation of Gynecologic Malignancies: Improving Treatment Delivery Using Aperture-Based Intensity-Modulated Radiotherapy  

SciTech Connect

Purpose: To evaluate dosimetric and treatment delivery advantages of aperture-based intensity-modulated radiotherapy (AB-IMRT) for the treatment of patients receiving whole pelvic radiotherapy for gynecologic malignancies. Methods and Materials: Nineteen patients undergoing pelvic radiotherapy after resection of endometrial cancers were selected. A 45-Gy dose was prescribed to the target volume delineated on a planning CT scan. An in-house inverse planning system, Ballista, was used to develop a treatment plan using aperture-based multileaf collimator segments. This approach was compared with conventional four-field, enlarged four-field, and static beamlet-based IMRT (BB-IMRT) techniques in terms of target coverage, dose-volume histogram statistics for surrounding normal tissues, and numbers of segments and monitor units (MU). Results: Three quarters (76.4%) of the planning target volume received the prescription dose with conventional four-field plans. With adequate target coverage, the Ballista plans significantly reduced the volume of bowel and bladder irradiated at the prescribed dose (p < 0.001), whereas the two approaches provided equivalent results for the rectum (p 0.5). On the other hand, AB-IMRT and BB-IMRT plans showed only small differences in dose-volume histogram statistics of unknown clinical impact, whereas Ballista plan delivery required on average 73% and 59% fewer segments and MU, respectively. Conclusion: With respect to conventional techniques, AB-IMRT for the treatment of gynecologic malignancies provides dosimetric advantages similar to those with BB-IMRT but with clear treatment delivery improvements.

Nadeau, Sylvain [Departement de physique, de genie physique et d'optique, Universite Laval, Quebec, QC (Canada) and Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada)]. E-mail: sylvainn@rrsb.nb.ca; Bouchard, Myriam [Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Germain, Isabelle [Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Raymond, Paul-Emile [Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Beaulieu, Frederic [Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Beaulieu, Luc [Departement de physique, de genie physique et d'optique, Universite Laval, Quebec, QC (Canada); Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Roy, Rene [Departement de physique, de genie physique et d'optique, Universite Laval, Quebec, QC (Canada); Gingras, Luc [Departement de physique, de genie physique et d'optique, Universite Laval, Quebec, QC (Canada); Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada)

2007-06-01

58

An accurate closed-form analytical model of single nanoshells for cancer treatment  

Microsoft Academic Search

Recently, there have been significant experimental advances in cancer treatment using metallic nanoshells, which are silica spheres coated with gold. Nanoshells posses an excellent tunability of their resonance frequency as a function of the relative sizes of the core and the thickness of the shell, consequently offering much improved sensitivity, specificity, and cost-effectiveness in cancer treatment. In this paper, we

Mehboob Alam; Yehia Massoud

2005-01-01

59

Organizational and financial issues in the delivery of substance abuse treatment services.  

PubMed

Examination of organizational and financial characteristics of the specialty substance abuse treatment system allows an understanding of how to meet the needs of clients in the system. Further, this assessment may afford insights into how the specialty sector may adapt in the changing environment of managed care. Data from Phase I of the Alcohol and Drug Services Study (ADSS) describe the specialty substance abuse treatment system in terms of type of care, setting, level of affiliation, licensure/accreditation, ownership, revenue sources, client referral sources, client's primary substance of abuse, and managed care. Although the system is largely outpatient and remains substantially two tiered in terms of public/private funding mix, it varies along a number of organizational and financial dimensions which have implications for system structure and facility viability in the changing environment of substance abuse treatment service delivery. PMID:11449759

Horgan, C M; Reif, S; Ritter, G A; Lee, M T

2001-01-01

60

Dosimetric variances anticipated from breathing- induced tumor motion during tomotherapy treatment delivery  

NASA Astrophysics Data System (ADS)

In their classic paper, Yu et al (1998 Phys. Med. Biol. 43 91) investigated the interplay between tumor motion caused by breathing and dynamically collimated, intensity-modulated radiation delivery. The paper's analytic model assumed an idealized, sinusoidal pattern of motion. In this work, we investigate the effect of tumor motion based on patients' breathing patterns for typical tomotherapy treatments with field widths of 1.0 and 2.5 cm. The measured breathing patterns of 52 lung- and upper-abdominal-cancer patients were used to model a one-dimensional motion. A convolution of the measured beam-dose profiles with the motion model was used to compute the dose-distribution errors, and the positive and negative dose errors were recorded for each simulation. The dose errors increased with increasing motion magnitude, until the motion was similar in magnitude to the field width. For the 1.0 cm and 2.5 cm field widths, the maximum dose-error magnitude exceeded 10% in some simulations, even with breathing-motion magnitudes as small as 5 mm and 10 mm, respectively. Dose errors also increased slightly with increasing couch speed. We propose that the errors were due to subtle drifts in the amplitude and frequency of breathing motion, as well as changes in baseline (exhalation) position, causing both over- and under-dosing of the target. The results of this study highlight potential breathing-motion-induced dose delivery errors in tomotherapy. However, for conventionally fractionated treatments, the dose delivery errors may not be co-located and may average out over many fractions, although this may not be true for hypofractionated treatments.

Chaudhari, S. R.; Goddu, S. M.; Rangaraj, D.; Pechenaya, O. L.; Lu, W.; Kintzel, E.; Malinowski, K.; Parikh, P. J.; Bradley, J. D.; Low, D. A.

2009-04-01

61

A novel liposomal nanomedicine for nitric oxide delivery and breast cancer treatment.  

PubMed

Breast cancer is the most common type of cancer occurring among women in the United States. Nitric oxide (NO) is endogenous signaling molecules that regulate biological processes. NO has the potential to induce either cancer progression or cancer cell apoptosis depending on intra-tumoral NO concentration. High levels of NO have a cytotoxic effect on cancer cells. A novel cytotoxic gas delivery system has been developed using NO-loaded echogenic liposomes (ELIP) for breast cancer treatment. Empty ELIP and NO-ELIP were prepared using the previously developed freezing-under-pressure method with modified lipid composition. Echogenicity of NO-ELIP was measured to determine the stability of NO-ELIP. Two types of breast cancer cell (BCC) lines, MDA-MB-231 and MDA-MB-468, were utilized. MTT assay was performed after NO-ELIP treatment to determine BCC viability. Echogenicity data demonstrated improved stability of NO-ELIP with the use of BSA for resuspension of NO-ELIP. Cell death induced by NO-ELIP was not from lipid cytotoxicity but from NO. The cytotoxic effect of NO-ELIP on BCC was highly dependent on NO-ELIP concentration. NO-ELIP in concentration of 1.0-2.0 mg/ml induced dramatically decreased BCC viability. This novel cytotoxic gas delivery nanomedicine using liposomal carriers, NO-ELIP, has the potential to provide improved therapeutic effect for breast cancer treatment. PMID:24211883

Lee, Soo Yeon; Rim, Yonghoon; McPherson, David D; Huang, Shao-Ling; Kim, Hyunggun

2014-01-01

62

Treatment of keloids with laser-assisted topical steroid delivery: a retrospective study of 23 cases.  

PubMed

Topical or intralesional corticosteroids are referred to as gold standard treatments for keloids. Recent studies showed that ablative fractional laser (AFL) treatment facilitates delivery of topical drug deeply into the skin by creating vertical channels. The objective of the present study was to assess the ablative erbium laser in fractionated mode, combined with topical high potent corticosteroid cream for treating resistant keloid scars. We conducted a retrospective study in the laser center of the Department of Dermatology (University Hospital of Nice, France), from January 2010 to June 2012, on patients with keloids who were resistant to a first-line of treatment. A 2940-nm ablative fractional erbium laser was used. Topical betamethasone cream was applied twice a day under occlusion with transparent film dressings. A total of 23 patients with 70 keloids were treated from January 2010 to June 2012. The median percentage of improvement was 50% (range -43 to 84). The mean follow-up was 8 months (range 3-18), and a recurrence was observed for eight lesions (22%). Although this observation warrants a prospective comparative evaluation, it supports the interest of the laser-assisted delivery of steroids for treating keloids scars. PMID:25471297

Cavalié, Marine; Sillard, Laura; Montaudié, Henri; Bahadoran, Philippe; Lacour, Jean-Philippe; Passeron, Thierry

2014-12-01

63

Retinoic Acid Promotes Interleukin-4 Plasmid-Dimethylsulfoxide Topical Transdermal Delivery for Treatment of Psoriasis  

PubMed Central

Background Psoriasis is an autoimmune disease that is caused by a shift in the Th1/Th2 balance toward Th1-dominant immunity. It has been established as an effective treatment to counteract psoriasis by subcutaneous injection of recombinant interleukin (IL)-4, and IL-4 gene therapy by topical transdermal penetration has shown its antipsoriatic effect in mice. Retinoic acid (RA) and dimethylsulfoxide can increase the efficiency of gene transfection in the topical transdermal delivery system. Objective We investigated whether RA could improve anti-psoriasis efficiency using IL-4 expression plasmid pORF-mIL-4 (pIL-4) via transdermal delivery system in K14-vascular endothelial growth (K14-VEGF) factor transgenic mice. Methods After pretreatment with RA, plasmid pIL-4 in 10% dimethylsulfoxide was applied to the ear skin by topical transdermal penetration. Hematoxylin- eosin staining and immunohistochemistry were performed with ear samples to evaluate anti-psoriasis efficiency in mice. Results The psoriasis pathological features were relieved and psoriasis-associated factors were significantly reduced. Conclusion Our results reveal that topical application of pIL-4 in dimethylsulfoxide by transdermal delivery with RA pretreatment can improve psoriasis significantly. PMID:25834349

Chen, Zhong-Wen; Zhang, Yin-Bing; Chen, Xaing-Jun; Liu, Xiao; Wang, Zhen; Zhou, Xi-Kun; Qiu, Ji; Zhang, Nan-Nan; Teng, Xiu; Mao, Yong-Qiu; Liu, Chang-Yong; Wei, Yu-Quan

2015-01-01

64

An electrospun scaffold integrating nucleic acid delivery for treatment of full thickness wounds  

PubMed Central

We developed a multi-functional construct capable of controlled delivery of bioactive substances that can improve wound repair by supporting the intrinsic ability of the skin to heal. We synthesized electrospun scaffolds—composed of a blend of the degradable polymers poly(L-lactide) (PLA) or polycaprolactone (PCL)—that produce highly efficient non-viral in vivo gene delivery to cells in the wound bed, provide a protective barrier during early wound healing, and support cell migration and growth. This multi-functional material was tested for its influence on wound healing: scaffolds were loaded with plasmids encoding keratinocyte growth factor (KGF) and applied to full thickness wounds in mice. Compared to scaffolds with control plasmids, animals receiving the KGF plasmid-loaded scaffold produced significant enhancements in wound healing, which was quantified by improvements in the rate of wound re-epithelialization, keratinocyte proliferation, and granulation response. Further, we quantified the expression level of endogenous and plasmid-derived KGF in wound samples: qRT-PCR on wound sections revealed a correlation between the levels of plasmid-derived protein expression and histological analysis of wound healing, revealing an inverse relationship between the expression level of exogenous KGF and the size of the unhealed epithelial layer in wounds. Our findings suggest that engineered nanofiber PLA/PCL scaffolds are capable of highly efficient controlled DNA delivery and are promising materials for treatment of cutaneous wounds. PMID:23453058

Kobsa, Serge; Kristofik, Nina J.; Sawyer, Andrew J.; Bothwell, Alfred L.M.; Kyriakides, Themis R.; Saltzman, W. Mark

2013-01-01

65

Efficacy of intracerebral delivery of cisplatin in combination with photon irradiation for treatment of brain tumors  

Microsoft Academic Search

We have evaluated the efficacy of intracerebral (i.c.) convection-enhanced delivery (CED) of cisplatin in combination with\\u000a photon irradiation for the treatment of F98 glioma-bearing rats. One thousand glioma cells were stereotactically implanted\\u000a into the brains of Fischer rats and 13 days later cisplatin (6 ?g\\/20 ?l) was administered i.c. by CED at a flow rate of 0.5 ?l\\/min.\\u000a On the following day the animals

Julia RousseauRolf; Rolf F. Barth; Manuel Fernandez; Jean-François Adam; Jacques Balosso; François Estève; Hélène Elleaume

2010-01-01

66

Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities  

NASA Astrophysics Data System (ADS)

Many tumor cells demonstrate hyperradiosensitivity at doses below ˜50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (˜20 cGy/pulse and effective dose rate 6.7 cGy min-1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min-1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (˜20 cGy arc-1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min-1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10-1.38 HI 1.04-1.10) and the VMAT (CI 1.08-1.26 HI 1.05-1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min-1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients.

Lin, Mu-Han; Price, Robert A., Jr.; Li, Jinsheng; Kang, Shengwei; Li, Jie; Ma, C.-M.

2013-11-01

67

Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities.  

PubMed

Many tumor cells demonstrate hyperradiosensitivity at doses below ~50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (~20 cGy/pulse and effective dose rate 6.7 cGy min?1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min?1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (~20 cGy arc?1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min?1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10–1.38; HI 1.04–1.10) and the VMAT (CI 1.08–1.26; HI 1.05–1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min?1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients. PMID:24200917

Lin, Mu-Han; Price, Robert A; Li, Jinsheng; Kang, Shengwei; Li, Jie; Ma, C-M

2013-11-21

68

Treatment delivery software for a new clinical grade ultrasound system for thermoradiotherapy.  

PubMed

A detailed description of a clinical grade Scanning Ultrasound Reflector Linear Array System (SURLAS) applicator was given in a previous paper [Med. Phys. 32, 230-240 (2005)]. In this paper we concentrate on the design, development, and testing of the personal computer (PC) based treatment delivery software that runs the therapy system. The SURLAS requires the coordinated interaction between the therapy applicator and several peripheral devices for its proper and safe operation. One of the most important tasks was the coordination of the input power sequences for the elements of two parallel opposed ultrasound arrays (eight 1.5 cm x 2 cm elements/array, array 1 and 2 operate at 1.9 and 4.9 MHz, respectively) in coordination with the position of a dual-face scanning acoustic reflector. To achieve this, the treatment delivery software can divide the applicator's treatment window in up to 64 sectors (minimum size of 2 cm x 2 cm), and control the power to each sector independently by adjusting the power output levels from the channels of a 16-channel radio-frequency generator. The software coordinates the generator outputs with the position of the reflector as it scans back and forth between the arrays. Individual sector control and dual frequency operation allows the SURLAS to adjust power deposition in three dimensions to superficial targets coupled to its treatment window. The treatment delivery software also monitors and logs several parameters such as temperatures acquired using a 16-channel thermocouple thermometry unit. Safety (in particular to patients) was the paramount concern and design criterion. Failure mode and effects analysis (FMEA) was applied to the applicator as well as to the entire therapy system in order to identify safety issues and rank their relative importance. This analysis led to the implementation of several safety mechanisms and a software structure where each device communicates with the controlling PC independently of the others. In case of a malfunction in any part of the system or a violation of a user-defined safety criterion based on temperature readings, the software terminates treatment immediately and the user is notified. The software development process consisting of problem analysis, design, implementation, and testing is presented in this paper. Once the software was finished and integrated with the hardware, the therapy system was extensively tested. Results demonstrated that the software operates the SURLAS as intended with minimum risk to future patients. PMID:16372408

Novák, Petr; Moros, Eduardo G; Straube, William L; Myerson, Robert J

2005-11-01

69

Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles  

NASA Astrophysics Data System (ADS)

Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V266ED3, rMcherry red) plasmids were constructed. Membrane anchoring and activity of designed proteins were analyzed in RAW264.7 Mo/Ma and HEK293 cells in vitro. Further, Urokinase (uPA) mediated cleavage and release of rCasp3V266ED3 from engineered cells was tested (Chapter-4). Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments. Final chapter of present report shows evidence for immune-deficient line of pigs as a model for human cancers (Chapter-5)

Balivada, Sivasai

70

QA Issues for Computer-Controlled Treatment Delivery: This Is Not Your Old R/V System Any More{exclamation_point}  

SciTech Connect

State-of-the-art radiotherapy treatment delivery has changed dramatically during the past decade, moving from manual individual field setup and treatment to automated computer-controlled delivery of complex treatments, including intensity-modulated radiotherapy and other similarly complex delivery strategies. However, the quality assurance methods typically used to ensure treatment is performed precisely and correctly have not evolved in a similarly dramatic way. This paper reviews the old manual treatment process and use of record-and-verify systems, and describes differences with modern computer-controlled treatment delivery. The process and technology used for computer-controlled treatment delivery are analyzed in terms of potential (and actual) problems, as well as relevant published guidance on quality assurance. The potential for improved quality assurance for computer-controlled delivery is discussed.

Fraass, Benedick A. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI (United States)], E-mail: bfraass@umich.edu

2008-05-01

71

Results of a UK survey on methods for compensating for unscheduled treatment interruptions and errors in treatment delivery.  

PubMed

In order to obtain a preliminary overview of the current national status regarding the management of both unintentional interruptions to radiotherapy treatments and inadvertent errors in treatment delivery, a short questionnaire was sent to 60 UK radiotherapy departments, of which 35 (58%) responded. The study was initiated by the authors and was not commissioned by any professional body. Amongst the centres which responded the majority (86%) currently have standardized protocols in place for dealing with treatment interruptions and many have extended the enactment of compensation methods to cover a wider range of tumour types than are encompassed within the Royal College of Radiologists (RCR)-defined Categories 1 and 2. Fewer of the respondents (60%) have standardized methods for dealing with treatment errors. Given that 42% of centres did not respond it is difficult to assess the fuller national picture. Some smaller departments may seek protocols or advice from larger adjacent centres, but the overall percentage of centres with systems in place may be lower than indicated from the survey results. The desirability of providing training in the radiobiological methods pertaining to treatment compensation was raised by a number of respondents. PMID:17267460

Dale, R G; Jones, B; Sinclair, J A; Comins, C; Antoniou, E

2007-05-01

72

Experimental verification of IMPT treatment plans in an anthropomorphic phantom in the presence of delivery uncertainties  

NASA Astrophysics Data System (ADS)

Clinically relevant intensity modulated proton therapy (IMPT) treatment plans were measured in a newly developed anthropomorphic phantom (i) to assess plan accuracy in the presence of high heterogeneity and (ii) to measure plan robustness in the case of treatment uncertainties (range and spatial). The new phantom consists of five different tissue substitute materials simulating different tissue types and was cut into sagittal planes so as to facilitate the verification of co-planar proton fields. GafChromic films were positioned in the different planes of the phantom, and 3D-IMPT and distal edge tracking (DET) plans were delivered to a volume simulating a skull base chordoma. In addition, treatments planned on CTs of the phantom with HU units modified were delivered to simulate systematic range uncertainties (range-error treatments). Finally, plans were delivered with the phantom rotated to simulate spatial errors. Results show excellent agreement between the calculated and the measured dose distribution: >99% and 98% of points with a gamma value <1 (3%/3 mm) for the 3D-IMPT and the DET plan, respectively. For both range and spatial errors, the 3D-IMPT plan was more robust than the DET plan. Both plans were more robust to range than to the spatial uncertainties. Finally, for range error treatments, measured distributions were compared to a model for predicting delivery errors in the treatment planning system. Good agreement has been found between the model and the measurements for both types of IMPT plan.

Albertini, F.; Casiraghi, M.; Lorentini, S.; Rombi, B.; Lomax, A. J.

2011-07-01

73

Cerclage, progesterone and ?-hydroxyprogeterone caproate treatment in women at risk for preterm delivery.  

PubMed

The most significant action of progesterone appears to be on the cervix and in prevention rather than on treatment of preterm delivery. In women with singleton gestations, no prior PTB, and CL <20?mm at <24 weeks, vaginal progesterone, either 90?mg gel or 200?mg suppository, is associated with reduction of both preterm birth (PTB) and perinatal morbidity/mortality. Cerclage is as effective as vaginal progesterone in women with CL <25?mm. Treatment of women with previous PTB with 17OHP-C from 16 to 20 weeks' gestation until 36 weeks could reduce significantly both the risk of delivery at <37, <35 and <32 weeks' gestation, as well as the rates of NEC, the need for supplemental oxygen and IVH. In women successfully treated with tocolytics progesterone combined with corticosteroid therapy lengthens pregnancy, reduces occurrence of respiratory distress syndrome and low birth weight. However, there is currently insufficient evidence on the role of progesterone after arrested preterm labor. It is reasonable to support an approach with CL screening of women with prior PTB starting at 16 to 19 weeks and administration of progesterone to women with a short cervix. Cerclage may be offered to those with a CL<25?mm. A combination of traditional tocolytics, corticosteroids and progesterone might be beneficial. PMID:24678618

Haram, Kjell; Mortensen, Jan Helge; Morrison, John C

2014-11-01

74

Treatment of chest wall tuberculosis with transdermal ultrasound-mediated drug delivery  

PubMed Central

Chest wall tuberculosis (TB) is an endemic disease with a large number of variants. The condition affects numerous parts of the body and can penetrate the skin to form chronic open ulcers. Current treatment methods include oral anti-TB drugs and surgery. However, conventional drug treatments are not effective due to the difficulty in achieving an effective local concentration, and certain patients are unable to tolerate surgery. The recurrence rate for chest wall TB is high following surgery, and may result in the prolonged healing of wounds in certain patients, as well as chronic sinusitis and fistula formation. To identify a safe, simple, less invasive and more clinically effective treatment method, the present study investigated transdermal ultrasound-mediated anti-TB drug delivery. A total of 186 patients were selected and randomly divided into transdermal ultrasound, surgery and oral anti-TB drug only groups. Rifampicin was the drug delivered by transdermal ultrasound. The cure and efficiency rates were shown to be 87.10 and 93.55%, respectively, in the ultrasound treatment group. No statistically significant difference was observed in the cure rates between the transdermal ultrasound and surgery groups; however, a statistically significant difference was identified in the cure rates between the transdermal ultrasound and oral anti-TB drug only groups. Therefore, transdermal ultrasound technology was shown to deliver anti-TB drugs quickly and directly, which resulted in a high local concentration of the drug, overcoming the problem of obtaining an effective local drug concentration. The observations demonstrated that transdermal ultrasound-mediated drug delivery is an effective method by which to control TB, particularly when compared with traditional oral anti-TB therapy and surgery. PMID:25780447

HAN, YI; ZHAO, QIUYUE; YU, DAPING; LIU, ZHIDONG

2015-01-01

75

Predisposing factors for bacterial vaginosis, treatment efficacy and pregnancy outcome among term deliveries; results from a preterm delivery study  

Microsoft Academic Search

BACKGROUND: Bacterial vaginosis (BV) during pregnancy is associated with an increased risk of preterm delivery but little is known about factors that could predict BV. We have analyzed if it is possible to identify a category of pregnant women that should be screened for BV, and if BV would alter the pregnancy outcome at term; we have also studied the

P-G Larsson; Lars Fåhraeus; Bodil Carlsson; Tell Jakobsson; Urban Forsum

2007-01-01

76

Down syndrome and dementia: Is depression a confounder for accurate diagnosis and treatment?  

PubMed

The past century has seen a dramatic improvement in the life expectancy of people with Down syndrome. However, research has shown that individuals with Down syndrome now have an increased likelihood of early onset dementia. They are more likely than their mainstream peers to experience other significant co-morbidities including mental health issues such as depression. This case study reports a phenomenon in which three individuals with Down syndrome and dementia are described as experiencing a rebound in their functioning after a clear and sustained period of decline. It is hypothesized that this phenomenon is not actually a reversal of the expected dementia trajectory but is an undiagnosed depression exaggerating the true level of functional decline associated with the dementia. The proactive identification and treatment of depressive symptoms may therefore increase the quality of life of some people with Down syndrome and dementia. PMID:25249377

Wark, Stuart; Hussain, Rafat; Parmenter, Trevor

2014-12-01

77

Delivery Unit Costs for Antiretroviral Treatment and Prevention of Mother-to-Child-Transmission of HIV  

PubMed Central

Background As antiretroviral treatment (ART) for HIV/AIDS is scaled-up globally, information on per-person costs is critical to improve efficiency in service delivery and maximize coverage and health impact. Objective To review studies on delivery unit costs for adult and pediatric ART provision per-patient-year, and prevention of mother-to-child transmission (PMTCT) interventions per mother-infant pair screened or treated, in low- and middle-income countries. Methods Systematic review of English, French and Spanish publications from 2001 to 2009, reporting empirical costing that accounted for at least antiretroviral (ARV) medicines, laboratory testing and personnel. Expenditures were analyzed by country income level and cost component. All costs were standardized to 2009 US dollars. Results Analyses covered 29 eligible, comprehensive costing studies. In the base case, in low-income countries (LIC), median, ART cost per patient-year was $792 (mean: $839, range: $682-$1089); for lower-middle-income countries (LMIC), the median was $932 (mean: $1246, range: $156-$3904); and for upper-middle-income countries (UMIC) the median was $1454 (mean: $2783, range: $1230-$5667). ARV drugs were largest component of overall ART cost in all settings (62%, 50% and 47% in LIC, LMIC and UMIC respectively). Out of 26 ART studies, 14 report which drug regimes were used, and only one study explicitly reported second line treatment costs. The second cost driver was laboratory cost in LIC and LMIC (14% and 19.5%) whereas it was personnel costs in UMIC (26%). Two studies specified the types of laboratory tests costed, and three studies specifically included above-facility-level personnel costs. Three studies reported detailed PMTCT costs, and two studies reported on pediatric ART. Conclusions There is a paucity of data on the full ART and PMTCT delivery unit costs, in particular for low-and middle-income countries. Heterogeneity in activities costed and insufficient detail regarding components included in the costing hampers standardization of unit cost measures. Evaluation of program-level unit costs would benefit from international guidance on standardized costing methods, and expenditure categories and definitions. Future work should help elucidate the sources for the large variations in delivery unit costs across settings with similar income and epidemiological characteristics. PMID:21671687

Galárraga, Omar; Wirtz, Veronika J.; Figueroa-Lara, Alejandro; Santa-Ana-Tellez, Yared; Coulibaly, Ibrahima; Viisainen, Kirsi; Medina-Lara, Antonieta; Korenromp, Eline L.

2013-01-01

78

A new pressure-controlled colon delivery capsule for chronotherapeutic treatment of nocturnal asthma.  

PubMed

The purpose of this study was to prepare a pressure-controlled colon delivery capsule (PCDC) containing theophylline (TPH) dispersion in a lipid matrix as a chronotherapeutic drug delivery system for the treatment of nocturnal asthma. The system was made by film coating using Eudragit S100- based formula over the sealed-hard gelatin capsules containing the drug-lipid dispersion. The lipid formula was composed mainly of Gelucire 33/01 (G33) with different ratios of surfactants (1-10%). The efficiency of the prepared system was evaluated in vitro for its ability to withstand both the gastric and intestinal medium. In addition, the drug plasma concentrations were monitored after single administration to Beagle dogs and compared to that obtained after administration of a reference marketed, generic, sustained-release TPH tablets, Avolen(®) SR. It was found that the optimum lipid formula was GL2 containing 90% G33 and 10% Labrasol. The film-coated capsules showed complete resistance to both the acidic environment (pH 1.2) for 2 hours and phosphate buffer pH 6.8 for 3 hours at 37°C. In vivo evaluation of the TPH-based PCDCs showed longer lag time compared TO the marketed formula followed by sudden increase in TPH blood levels, which recommends the high potential of this system as a chronotherapeutic drug delivery for nocturnal asthma. The prepared PCDCs exhibited a significantly higher C(max) and T(max) and a nonsignificantly different AUC compared with Avolen(®) SR. Higher TPH blood levels from 1 to 8 hours postadministration was detected in the case of the prepared PCDCs. PMID:20681754

Barakat, Nahla S; Al-Suwayeh, Saleh A; Taha, Ehab I; Bakry Yassin, Alaa Eldeen

2011-06-01

79

Improving consistency and quality of service delivery: implications for the addiction treatment field.  

PubMed

Addiction treatment providers face serious problems in delivering consistent, high-quality services over time. Among those providers with multiple treatment sites, there is also intersite variability. This is a serious problem in the addiction field, likely to be made worse as new technologies are introduced and/or as there is industry consolidation (Corredoira, R., Kimberly, J. (2006) Industry evolution through consolidation: Implications for addiction treatment. Journal of Substance Abuse Treatment 31, 255-265.). Although serious, these problems in managing and monitoring to assure consistent service quality have been faced by many other industries. Here, we review evidence from research in other industries regarding three different forms of management (vertical integration, franchising, and licensing) across a chain of individual service providers. We show how each management form affects the level, consistency, and improvement of service delivery over time. In addition, we discuss how such performance advantages affect customer demand as well as regulatory endorsement of the consolidated firm and its approach. PMID:18082996

Knott, Anne Marie; Corredoira, Rafael; Kimberly, John

2008-09-01

80

An Overview on Dry Eye Treatment: Approaches for Cyclosporin A Delivery  

PubMed Central

Dry eye syndrome (DES, Keratoconjunctivitis sicca) is a common disorder of the tear film caused by decreased tear production or increased evaporation. Changes in tear composition also promote inflammation on the ocular surface by various mechanisms. Artificial tear drops, tear retention treatment, stimulation of tear secretion, or anti-inflammatory drugs may be used for dry eye treatment according to the severity of the disease. For untreated patients, the risk of ocular infection increases at considerable level and clinical course of the disease may proceed up to infection, corneal ulcer, and blindness. Artificial tears and/or punctual occlusions are used for tear replacement or preservation. New treatment approaches are designed to modify the underlying disease process. For the treatment of severe dry eye disease, cyclosporin A (CsA), the first one of the new generation immunomodulatory drugs, which has an anti-inflammatory effect, is frequently used. CsA has immunosuppressive effects following systemic application. Following local administration of CsA, it is expected to obtain effective drug concentration at the target area and to avoid the various side effects associated with systemic delivery. Microspheres, implants, and liposomes have been developed for administration of CsA subconjunctivally in order to enhance its efficiency. PMID:22619624

Yavuz, Burçin; Bozda? Pehlivan, Sibel; Ünlü, Nur?en

2012-01-01

81

The role of Cobalt-60 source in Intensity Modulated Radiation Therapy: From modeling finite sources to treatment planning and conformal dose delivery  

NASA Astrophysics Data System (ADS)

Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen's University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system are deliverable. Comparing the Co-60 dose distributions and DVHs to the IMRT plans from the clinic indicates that Co-60 is able to provide similar dose conformality to targets and dose sparing to critical organs. The results of the novel MLC segmentation algorithm and the photon fluence model proposed in this work compared well with the Monte Carlo calculations. In summary, the investigations presented in this thesis confirm that Co-60 tomotherapy is indeed capable of providing state-of-the-art conformal dose delivery. We have shown that the perceived beam limitations often identified with Co-60 (e.g., lower penetration, source size artifacts under small field collimation, and larger penumbra) are negligible when using intensity modulated techniques.

Dhanesar, Sandeep Kaur

82

Treatment planning and dosimetric comparison study on two different volumetric modulated arc therapy delivery techniques  

PubMed Central

Aim To compare and evaluate the performance of two different volumetric modulated arc therapy delivery techniques. Background Volumetric modulated arc therapy is a novel technique that has recently been made available for clinical use. Planning and dosimetric comparison study was done for Elekta VMAT and Varian RapidArc for different treatment sites. Materials and methods Ten patients were selected for the planning comparison study. This includes 2 head and neck, 2 oesophagus, 1 bladder, 3 cervix and 2 rectum cases. Total dose of 50 Gy was given for all the plans. All plans were done for RapidArc using Eclipse and for Elekta VMAT with Monaco treatment planning system. All plans were generated with 6 MV X-rays for both RapidArc and Elekta VMAT. Plans were evaluated based on the ability to meet the dose volume histogram, dose homogeneity index, radiation conformity index, estimated radiation delivery time, integral dose and monitor units needed to deliver the prescribed dose. Results RapidArc plans achieved the best conformity (CI95% = 1.08 ± 0.07) while Elekta VMAT plans were slightly inferior (CI95% = 1.10 ± 0.05). The in-homogeneity in the PTV was highest with Elekta VMAT with HI equal to 0.12 ± 0.02 Gy when compared to RapidArc with 0.08 ± 0.03. Significant changes were observed between the RapidArc and Elekta VMAT plans in terms of the healthy tissue mean dose and integral dose. Elekta VMAT plans show a reduction in the healthy tissue mean dose (6.92 ± 2.90) Gy when compared to RapidArc (7.83 ± 3.31) Gy. The integral dose is found to be inferior with Elekta VMAT (11.50 ± 6.49) × 104 Gy cm3 when compared to RapidArc (13.11 ± 7.52) × 104 Gy cm3. Both Varian RapidArc and Elekta VMAT respected the planning objective for all organs at risk. Gamma analysis result for the pre-treatment quality assurance shows good agreement between the planned and delivered fluence for 3 mm DTA, 3% DD for all the evaluated points inside the PTV, for both VMAT and RapidArc techniques. Conclusion The study concludes that a variable gantry speed with variable dose rate is important for efficient arc therapy delivery. RapidArc presents a slight improvement in the OAR sparing with better target coverage when compared to Elekta VMAT. Trivial differences were noted in all the plans for organ at risk but the two techniques provided satisfactory conformal avoidance and conformation. PMID:24416535

Kumar, S.A. Syam; Holla, Raghavendra; Sukumar, Prabakar; Padmanaban, Sriram; Vivekanandan, Nagarajan

2012-01-01

83

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

NASA Astrophysics Data System (ADS)

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

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

2007-07-01

84

Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems  

PubMed Central

Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease(AD), are a group of pathologies characterized by a progressive and specific loss of certain brain cell populations. Oxidative stress, mitochondrial dysfunction, and apoptosis play interrelated roles in these disorders. It is well documented that free radical oxidative damage, particularly on neuronal lipids, proteins, DNA, and RNA, is extensive in PD and AD brains. Moreover, alterations of glutathione (GSH) metabolism in brain have been implicated in oxidative stress and neurodegenerative diseases. As a consequence, the reduced GSH levels observed in these pathologies have stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels. Unfortunately, GSH delivery to the central nervous system (CNS) is limited due to a poor stability and low bioavailability. Medicinal-chemistry- and technology-based approaches are commonly used to improve physicochemical, biopharmaceutical, and drug delivery properties of therapeutic agents. This paper will focus primarily on these approaches used in order to replenish intracellular GSH levels, which are reduced in neurodegenerative diseases. Here, we discuss the beneficial properties of these approaches and their potential implications for the future treatment of patients suffering from neurodegenerative diseases, and more specifically from PD and AD. PMID:22701755

Cacciatore, Ivana; Baldassarre, Leonardo; Fornasari, Erika; Mollica, Adriano; Pinnen, Francesco

2012-01-01

85

Sustained delivery of cytarabine-loaded vesicular phospholipid gels for treatment of xenografted glioma.  

PubMed

This study described the development of vesicular phospholipid gels (VPGs) for sustained delivery of cytarabine (Ara-C) for the treatment of xenografted glioma. Ara-C-loaded VPGs in the state of a semisolid phospholipid dispersion looked like numerous vesicles tightly packing together under the freeze-fracture electron microscopy (FF-TEM), their release profiles displayed sustained drug release up to 384 h in vitro. The biodistribution of Ara-C in the rat brain showed that Ara-C-loaded VPGs could maintain therapeutic concentrations up to 5mm distance from the implantation site in brain tissue within 28 days. At the same time, fluorescence micrograph confirmed drug distribution in brain tissue visually. Furthermore, after single administration, Ara-C-loaded VPGs group significantly inhibited the U87-MG glioma growth in right flank in comparison with Ara-C solution (p<0.01). It was explained that the entrapped drug in VPGs could avoid degradation from cytidine deaminase and sustained release of drug from Ara-C-loaded VPGs could maintain the effective therapeutic levels for a long time around the tumor. In conclusion, Ara-C-loaded VPGs, with the properties of sustained release, high penetration capacity, nontoxicity and no shape restriction of the surgical cavity, are promising local delivery systems for post-surgical sustained chemotherapy against glioma. PMID:24914829

Qi, Na; Cai, Cuifang; Zhang, Wei; Niu, Yantao; Yang, Jingyu; Wang, Lihui; Tian, Bin; Liu, Xiaona; Lin, Xia; Zhang, Yu; Zhang, Yan; He, Haibing; Chen, Kang; Tang, Xing

2014-09-10

86

Cobalt-60 tomotherapy: Clinical treatment planning and phantom dose delivery studies  

SciTech Connect

Purpose: Investigations have shown that a Cobalt-60 (Co-60) radioactive source has the potential to play a role in intensity modulated radiation therapy (IMRT). In this paper, Co-60 tomotherapy's conformal dose delivery potential is evaluated by delivering conformal dose plans on a cylindrical homogeneous phantom containing clinical structures similar to those found in a typical head and neck (H and N) cancer. Also, the clinical potential of Co-60 tomotherapy is investigated by generating 2D clinical treatment plans for H and N and prostate anatomical regions. These plans are compared with the 6 MV based treatment plans for modalities such as linear accelerator-based tomotherapy and broad beam IMRT, and 15 MV based 3D conformal radiation therapy (3DCRT).Methods: For experimental validation studies, clinical and nonclinical conformal dose patterns were delivered on circular, homogeneous phantoms containing GafChromic film. For clinical planning study, dose calculations were performed with the EGSnrc Monte Carlo program, where a Theratronics 780C Co-60 unit and a 6 MV linear accelerator were modeled with a MIMiC binary multileaf collimator. An inhouse inverse treatment planning system was used to optimize tomotherapy plans using the same optimization parameters for both Co-60 and 6 MV beams. The IMRT and 3DCRT plans for the clinical cases were generated entirely in the Eclipse treatment planning system based on inhouse IMRT and 3DCRT site specific protocols.Results: The doses delivered to the homogeneous phantoms agreed with the calculations, indicating that it is possible to deliver highly conformal doses with the Co-60 unit. The dose distributions for Co-60 tomotherapy clinical plans for both clinical cases were similar to those obtained with 6 MV based tomotherapy and IMRT, and much more conformal compared to 3DCRT plans. The dose area histograms showed that the Co-60 plans achieve the dose objectives for the targets and organs at risk.Conclusions: These results confirm that Co-60 tomotherapy is capable of providing state-of-the-art conformal dose delivery and could be used for the treatment of targets in both small and larger separation anatomical regions.

Dhanesar, Sandeep; Darko, Johnson; Joshi, Chandra P.; Kerr, Andrew; John Schreiner, L. [Department of Physics and Department of Oncology, Queen's University, Kingston, Ontario K7L3N6, Canada and Medical Physics Department, Cancer Center of Southeastern Ontario, Kingston, Ontario K7L5P9 (Canada)] [Department of Physics and Department of Oncology, Queen's University, Kingston, Ontario K7L3N6, Canada and Medical Physics Department, Cancer Center of Southeastern Ontario, Kingston, Ontario K7L5P9 (Canada)

2013-08-15

87

Gene and drug delivery system and potential treatment into inner ear for protection and regeneration.  

PubMed

The most common type of hearing loss results from damage to the cochlea including lost hair cells (HCs) and spiral ganglion neurons (SGNs). In mammals, cochlear HC loss causes irreversible hearing impairment because this type of sensory cell cannot regenerate. The protection from SGN from degeneration has implications for cochlear implant to patients with severe deafness. This review summarizes the several treatments for HC regeneration based on experiments. We discuss how transgene expression of the neurotrophic factor can protect SGN from degeneration and describe potential new therapeutic interventions to reduce hearing loss. We also summarized viral vectors and introduced the gene and drug delivery system for regeneration and protection of cochlear HCs. Finally, we introduce the novel endoscopy we developed for local injection into cochlea. PMID:25339903

Kanzaki, Sho

2014-01-01

88

Gene and drug delivery system and potential treatment into inner ear for protection and regeneration  

PubMed Central

The most common type of hearing loss results from damage to the cochlea including lost hair cells (HCs) and spiral ganglion neurons (SGNs). In mammals, cochlear HC loss causes irreversible hearing impairment because this type of sensory cell cannot regenerate. The protection from SGN from degeneration has implications for cochlear implant to patients with severe deafness. This review summarizes the several treatments for HC regeneration based on experiments. We discuss how transgene expression of the neurotrophic factor can protect SGN from degeneration and describe potential new therapeutic interventions to reduce hearing loss. We also summarized viral vectors and introduced the gene and drug delivery system for regeneration and protection of cochlear HCs. Finally, we introduce the novel endoscopy we developed for local injection into cochlea. PMID:25339903

Kanzaki, Sho

2014-01-01

89

pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment  

PubMed Central

In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles (MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanoparticles, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail. PMID:24738037

Yang, Ke-Ni; Zhang, Chun-Qiu; Wang, Wei; Wang, Paul C.; Zhou, Jian-Ping; Liang, Xing-Jie

2014-01-01

90

Bone grafts as carriers for local antibiotic delivery for the treatment and prevention of bone infections.  

PubMed

Osteomyelitis is a bone infection accompanied by inflammatory process, which can lead to destruction and bone necrosis. It is difficult to manage, and there are no commonly accepted guidelines. While most acute bone infections are usually successfully treated with intravenous antibiotics, chronic infections and infections in the presence of foreign materials usually require operative treatment with debridement, removal of metals, intravenous antibiotics, and very often local antibiotics. The aim of this study was to perform a systematic review of the existing literature concerning the use of bone grafts as carriers for local antibiotic delivery for the treatment and prevention of bone infections. According to the literature, antibiotic-loaded autologous bone grafts for the treatment of infected tibial nonunion is a good option (Grade-B recommendations). Although there are several studies concerning the use of antibiotic-loaded allogenic bone grafts in infected joint arthroplasty revisions, there is a lack of comparative studies (Grade-C recommendations). Studies concerning spinal fusion and spondylodiscitis are limited (Grade-I recommendations). PMID:25433347

Lalidou, Fani; Kolios, George; Tavridou, Anna; Drosos, Georgios I

2014-11-01

91

Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs.  

PubMed

Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet non-specific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20kHz and 1MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20kHz alone. Additionally, LTRs generated by treatment with 20kHz+1MHz were found to be more permeable than those generated with 20kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20kHz+1MHz were calculated to be significantly larger than the pores in skin treated with 20kHz alone. This demonstrates for the first time that LTRs generated with 20kHz+1MHz are also more permeable than those generated with 20kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20kHz+1MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo. PMID:25662228

Schoellhammer, Carl M; Srinivasan, Sharanya; Barman, Ross; Mo, Stacy H; Polat, Baris E; Langer, Robert; Blankschtein, Daniel

2015-03-28

92

Innovative Technology for the Assisted Delivery of Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson Disease  

ERIC Educational Resources Information Center

Purpose: To assess the feasibility and effectiveness of a newly developed assistive technology system, Lee Silverman Voice Treatment Companion (LSVT[R] Companion[TM], hereafter referred to as "Companion"), to support the delivery of LSVT[R]LOUD, an efficacious speech intervention for individuals with Parkinson disease (PD). Method: Sixteen…

Halpern, Angela E.; Ramig, Lorraine O.; Matos, Carlos E. C.; Petska-Cable, Jill A.; Spielman, Jennifer L.; Pogoda, Janice M.; Gilley, Phillip M.; Sapir, Shimon; Bennett, John K.; McFarland, David H.

2012-01-01

93

Child Sexual Abuse Prevention and Treatment Service Delivery Problems and Solutions in Rural Areas of Washington State.  

ERIC Educational Resources Information Center

This study investigates prevention and treatment programs that deal with rural child sexual abuse in the State of Washington. A survey of 61 rural service providers examined agencies, services provided, problems faced in service delivery, and innovative solutions to those problems. The study compares responses from three types of agencies (mental…

Ray, JoAnn; Murty, Susan A.

94

Methotrexate transport mechanisms: the basis for targeted drug delivery and ß-folate-receptor-specific treatment.  

PubMed

Methotrexate (MTX) plays a pivotal role in the treatment of rheumatoid arthritis (RA). The transport mechanisms with which MTX reaches is target after application are an important part of MTX pharmacology and its concentration in target tissue such as RA synovial membrane might strongly influence the effectiveness of the drug. Physiological plasma protein binding of MTX to albumin is important for the distribution of MTX in the body and relative high concentrations of the drug are found in the liver. However, targeted drug delivery into inflamed joints and increased anti-arthritic efficiency can be obtained by covalent coupling of MTX ex-vivo to human serum albumin (MTX-HSA) or in-vivo to endogenous albumin mediated through the MTX-pro-drug AWO54. High expression of the folate receptor ? (FR-?) on synovial macrophages of RA patients and its capacity to mediate binding and uptake of MTX has been demonstrated. To further improve drug treatment of RA, FR-? specific drugs have been developed and were characterised for their therapeutic potency in synovial inflammation. Therefore, different approaches to improve folate inhibitory and FR-? specific therapy of RA beyond MTX are in development and will be described. PMID:21044432

Fiehn, C

2010-01-01

95

Developments on drug delivery systems for the treatment of mycobacterial infections.  

PubMed

The clinical management of tuberculosis and other mycobacterial diseases with antimycobacterial chemotherapy remains a difficult task. The classical treatment protocols are long-lasting; the drugs reach mycobacteria-infected macrophages in low amounts and/or do not persist long enough to develop the desired antimycobacterial effect; and the available agents induce severe toxic effects. Nanotechnology has provided a huge improvement to pharmacology through the designing of drug delivery systems able to target phagocytic cells infected by intracellular pathogens, such as mycobacteria. Liposomes and nanoparticles of polymeric nature represent two of the most efficient drug carrier systems that after in vivo administration are endocytosed by phagocytic cells and then release the carried agents into these cells. This article reviews the relevant publications describing the effectiveness of the association of antimycobacterial agents with liposomes or nanoparticles for the treatment of mycobacterioses, particularly for Mycobacterium tuberculosis and M. avium infections. The increased therapeutic index of antimycobacterial drugs; the reduction of dosing frequency; and the improvement of solubility of hydrophobic agents, allowing the administration of higher doses, have been demonstrated in experimental infections. These advantages may lead to new therapeutic protocols that will improve patient compliance and, consequently, lead to a more successful control of mycobacterial infections. The potential therapeutic advantages resulting from the use of non-invasive administration routes for nanoparticulate systems are also discussed. PMID:18473884

Gaspar, M M; Cruz, A; Fraga, A G; Castro, A G; Cruz, M E M; Pedrosa, J

2008-01-01

96

Telomerase inhibitors for the treatment of brain tumors and the potential of intranasal delivery.  

PubMed

A fundamental limitation in the treatment of brain tumors is that < 1% of most therapeutic agents administered systemically are able to cross the blood-brain barrier (BBB). The development of new strategies that circumvent the BBB should increase the likelihood of tumor response to selected therapeutic agents. Intranasal delivery (IND) is a practical, noninvasive method of bypassing the BBB to deliver therapeutic agents to the brain. This technique has demonstrated promising results in the treatment of neurological disorders. Telomerase is a reverse transcriptase that is expressed in the vast majority of malignant gliomas, although not in the healthy brain. Telomerase inhibition can therefore be used as a therapeutic strategy for selectively targeting malignant gliomas. The first successful IND of a telomerase inhibitor as a therapy for brain tumors was GRN-163, an oligonucleotide N3'-->5' thiophosphoramidate telomerase inhibitor, which was successfully administered into intracerebral tumors in rats with no apparent toxicity. GRN-163 exhibited favorable tumor uptake and inhibited tumor growth, leading to prolonged lifespan in treated animals. The IND of telomerase inhibitors represents a new therapeutic approach that appears to selectively kill tumor cells, without inducing toxic effects in the surrounding healthy brain tissue. PMID:20373260

Hashizume, Rintaro; Gupta, Nalin

2010-04-01

97

The effect of autophagy inhibitors on drug delivery using biodegradable polymer nanoparticles in cancer treatment.  

PubMed

Nanoparticles of biodegradable polymers (NPs) have been widely used for drug delivery. However, there has been little research on their fate after internalized into the cells. We show in this research by using docetaxel as a model anticancer drug, which is formulated in the cholic acid conjugated nanoparticles of poly(lactic-co-glycolic acid (PLGA NPs) that the NPs induce autophagy of the cancer cells and thus may hinder the advantages of the nanomedicine. Moreover, we show both in vitro and in vivo that co-administration of autophagy inhibitors such as 3-methyladenine (3-MA) and Chloroquine (CQ) could greatly enhance the therapeutic effects of the nanoparticle formulation. The IC50 values of the drug formulated in the PLGA NPs after 24 h treatment with no autophagy inhibitor or in combination with 10 mm 3-MA or 30 ?m CQ are 38.27 ± 1.23, 6.7 ± 1.05, 4.78 ± 1.75 ?g/mL, which implie 5.7 or 8,0 fold efficient by the autophagy inhibition respectively. Moreover, both the volume and the weight of the shrunk tumor of the mice after 20 day treatment with the PLGA NPs formulation combined with 3-MA or CQ are found to be only about a half in comparison with the treatment with the PLGA NPs formulation alone. In this research, we reported such a new mechanism of cancer cells to have PLGA NPs captured and degraded by auto-lysosomes. The findings provide advanced knowledge for development of nanomedicine for clinical application. PMID:24315578

Zhang, Xudong; Dong, Yichen; Zeng, Xiaowei; Liang, Xin; Li, Xiaoming; Tao, Wei; Chen, Hongbo; Jiang, Yuyang; Mei, Lin; Feng, Si-Shen

2014-02-01

98

Relaxin treatment of solid tumors: effects on electric field-mediated gene delivery.  

PubMed

Pulsed electric fields have been shown to enhance interstitial transport of plasmid DNA (pDNA) in solid tumors in vivo. However, the extent of enhancement is still limited partly due to the collagen component in extracellular matrix. To this end, effects of collagen remodeling on interstitial electrophoresis were investigated by pretreatment of tumor-bearing mice with a recombinant human relaxin (rh-Rlx). In the study, two tumor lines (4T1 and B16.F10) were examined and implanted s.c. to establish two murine models: dorsal skin-fold chamber (DSC) and hind leg. Effects of rh-Rlx on pDNA electrophoresis were measured either directly in the DSC model or indirectly in the hind leg model via reporter gene expression. It was observed that rh-Rlx treatment reduced collagen levels in the hind leg tumors but not in the DSC tumors. The observation correlated with the results from electromobility experiments, where rh-Rlx treatment enhanced transgene expression in 4T1 hind leg tumors but did not increase the electromobility of pDNA in the DSC tumors. In addition, it was observed that pDNA binding to collagen could block its diffusion in collagen gel in vitro. These observations showed that effects of rh-Rlx on the collagen content depended on microenvironment in solid tumors and that rh-Rlx treatment would enhance electric field-mediated gene delivery only if it could effectively reduce the collagen content in collagen-rich tumors. PMID:18723501

Henshaw, Joshua; Mossop, Brian; Yuan, Fan

2008-08-01

99

Increased prevalence of dhfr and dhps mutants at delivery in Malawian pregnant women receiving intermittent preventive treatment for malaria  

PubMed Central

Summary In the context of an Intermittent preventive treatment (IPTp) trial for pregnant women in Malawi, P. falci-parum samples from 85 women at enrollment and 35 women at delivery were genotyped for mutations associated with sulfadoxine-pyrimethamine resistance. The prevalence of the highly resistant haplotype with mutations at codons 51 and 108 of dihydrofolate reductase (dhfr) and codons 437 and 540 of dihydropteroate synthase (dhps) increased from 81% at enrollment to 100% at delivery (p=0.01). Pregnant women who were smear-positive at enrollment were more likely to have P. falciparum parasitemia at delivery. These results lend support to concerns that IPTp use may lead to increased drug resistance in pregnant women during pregnancy and emphasize the importance of screening pregnant women for malaria parasites in areas with prevalent SP resistance even when they are already on IPTp. PMID:23198734

Lin, Jessica T.; Mbewe, Bernard; Taylor, Steve M.; Luntamo, Mari; Meshnick, Steven R.; Ashorn, Per

2012-01-01

100

Increased prevalence of dhfr and dhps mutants at delivery in Malawian pregnant women receiving intermittent preventive treatment for malaria.  

PubMed

In the context of an Intermittent preventive treatment (IPTp) trial for pregnant women in Malawi, Plasmodium falciparum samples from 85 women at enrollment and 35 women at delivery were genotyped for mutations associated with sulfadoxine-pyrimethamine resistance. The prevalence of the highly resistant haplotype with mutations at codons 51 and 108 of dihydrofolate reductase (dhfr) and codons 437 and 540 of dihydropteroate synthase (dhps) increased from 81% at enrollment to 100% at delivery (P = 0.01). Pregnant women who were smear-positive at enrollment were more likely to have P. falciparum parasitemia at delivery. These results lend support to concerns that IPTp use may lead to increased drug resistance in pregnant women during pregnancy and emphasise the importance of screening pregnant women for malaria parasites in areas with prevalent SP resistance even when they are already on IPTp. PMID:23198734

Lin, Jessica T; Mbewe, Bernard; Taylor, Steve M; Luntamo, Mari; Meshnick, Steven R; Ashorn, Per

2013-02-01

101

Types of Nasal Delivery Drugs and Medications in Iranian Traditional Medicine to Treatment of Headache  

PubMed Central

Context: Headache is a common symptom throughout the world. The main purpose of patient-centered approaches is the utilization of useful and simple treatment. Nowadays, there is a rising propensity toward herbal remedies. Nasal route is one of the ancient and topical prescriptions used in headache. In Iranian traditional medicine, physicians such as Avicenna were prescribing herbal drugs through the nose to treat a variety of central nervous system diseases like headache. In this review paper, authors have attempted to introduce different types of nasal administrations which were used in Iranian traditional medicine for the treatment of headaches. Evidence Acquisition: Initially, we studied two different types of Canon and separated all herbs used in the treatment of headache. Next, all plants were classified according to the method of prescription. Then, we pick out all the plants which were nasally utilized in the treatment of headache and divided them based on the method of administration. In order to find scientific names of herbs, we used two different botany references. Moreover, we conducted various researches in scientific databases with the aim of finding results concerning the analgesic and antinociceptive effects of herbs. Throughout the research, key terms were “analgesic” and “antinociceptive “with the scientific names of all herbs separately. The databases searched included PubMed, Scopus, Cochrane library and SID. Results: 35 plants were prescribed for the treatment of headaches, which were all nasally used. These plants took either the form of powder, liquid or gas (steam). They were divided in to six categories according to the method of prescription. The Percentage of usage for each method was as follows: 62% Saoot (nasal drop), 25% Shamoom (smell), 17% Inkabab (vapor), 11% Nafookh (snuff), 11% Nashooq (inhaling) and 2% Bokhoor (smoke). Conclusions: Medications that are used via nasal delivery have greater effect than oral medications. Iranian physicians were fully aware of systemic effects of topical medications, including prescription drugs through the nose. The study of ancient medical texts helps us in identification of herbal medicine and the investigation of new way for the preparation of drugs. PMID:25068043

Ghorbanifar, Zahra; Delavar Kasmaei, Hosein; Minaei, Bagher; Rezaeizadeh, Hossein; Zayeri, Farid

2014-01-01

102

Risk of Preterm Delivery Associated with Prior Treatment of Cervical Precancerous Lesion according to the Depth of the Cone  

PubMed Central

The aim of this study was to evaluate the impact of the surgical excisional procedures for cervical intraepithelial neoplasia (CIN) treatment both on subsequent fertility (cervical factor) and pregnancy complication (risk of spontaneous preterm delivery). We retrospectively analyzed 236 fertile women who underwent conization for CIN. We included in the study 47 patients who carried on pregnancy and delivered a viable fetus. Patients were asked about postconization pregnancies, obstetrical outcomes, and a possible diagnosis of secondary infertility caused by cervical stenosis. We evaluated the depth of surgical excision, the timing between cervical conization and subsequent pregnancies, surgical technique, and maternal age at delivery. We recorded 47 deliveries, 10 cases of preterm delivery; 8 of them were spontaneous. The depth of surgical excision showed a statistically significant inverse correlation with gestational age at birth. The risk of spontaneous preterm delivery increased when conization depth exceeded a cut-off value of 1.5?cm. Our data do not demonstrated a relation between conization and infertility due to cervical stenosis. PMID:24324288

Berretta, Roberto; Gizzo, Salvatore; Dall'Asta, Andrea; Mazzone, Eleonora; Monica, Michela; Franchi, Laura; Peri, Francesca; Patrelli, Tito Silvio; Bacchi Modena, Alberto

2013-01-01

103

Nanoparticulate delivery of LHRH analogue for the treatment of prostate cancer.  

PubMed

Goserelin acetate (Gos) is a luteinizing hormone-releasing hormone agonist, used in treatment of prostate cancer in which desired concentration of Gos in blood is maintained for longer duration. The aim of this study is to improve the efficacy of Gos targeted at the site of action and eliminate the need for frequent administration. Gos-encapsulated nanoparticles were fabricated by double emulsification process. The physicochemical traits of the nanoparticles including morphology, particle size, zeta-potential, entrapment efficiency, and in-vitro release profile were studied. The in-vitro cytotoxicity of the blank nanoparticles and Gos-loaded nanoparticles were also evaluated on LNCaP cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Blank methoxy PEG-poly(?-caprolactone) (mPEG-PCL) nanoparticles exhibited low cytotoxicity, which increased with increase in concentration of Gos-loaded nanoparticles. Serum Gos and testosterone levels were analyzed after subcutaneous administration in Wistar rats. In-vivo study showed that a sustained serum level of Gos successfully suppressed the plasma testosterone concentration to castration level. So, it can be concluded that mPEG-PCL nanoparticles might prove to be useful for site specific and sustain protein delivery. PMID:22380019

Tomar, Priti; Jain, Neeti; Dixit, Vinod Kumar

2013-01-01

104

Biopolymer-based transdermal films of donepezil as an alternative delivery approach in Alzheimer's disease treatment.  

PubMed

Matrix type transdermal films of donepezil (DNP) as an alternative delivery approach was designed to improve patient compliance to Alzheimer disease treatment. Sodium alginate, a natural polysaccharide, was used as matrix-forming agent in the optimization of transdermal films. Propylene glycol and dl-limonene was added into films as a plasticizer and permeation enhancer, respectively. As well as mechanical strength and bioadhesiveness of optimized transdermal films of DNP, the impact of dl-limonene concentration in films on DNP in vitro permeation across pig skin was assessed. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) measurements were carried out to examine the effects of enhancer on in vitro conformational order of the stratum corneum intercellular lipids following permeation study. Results showed that transdermal formulations of DNP were suitable due to both mechanical and bioadhesive features of the films. In vitro skin permeation study indicated that dl-limonene at a concentration of 3% was optimum with high drug flux. ATR-FTIR results confirmed a more fluidized stratum corneum lipid state in the presence of dl-limonene, indicating its permeation enhancement effect. Regarding to achieve therapeutic levels of DNP, it seems to be feasible deliver DNP with transdermal films for the management of Alzheimer disease. PMID:25273029

Galipo?lu, Maviye; Erdal, Meryem Sedef; Güngör, Sevgi

2015-04-01

105

Biomimetic nanoparticles for siRNA delivery in the treatment of leukaemia.  

PubMed

Leukaemia is a bone marrow cancer occurring in acute and chronic subtypes. Acute leukaemia is a rapidly fatal cancer potentially causing death within a few weeks, if untreated. Leukaemia arises as a result of disruption to haematopoietic precursors, caused either by acquired gene fusions, gene mutations or inappropriate expression of the relevant oncogenes. Current treatment options have made significant progress, but the 5 year survival for acute leukaemia remains under 10% in elderly patients, and less than 50% for some types of acute leukaemia in younger adults. For chronic leukaemias longer survival is generally expected and for chronic myeloid leukaemia patients on tyrosine kinase inhibitors the median survival is not yet reached and is expected to exceed 10 years. Chemotherapy and haematopoietic stem cell transplantation (HSCT) for acute leukaemia provide the mainstay of therapy for patients under 65 and both carry significant morbidity and mortality. Alternative and superior therapeutic strategies for acute leukaemias are urgently required. Recent molecular-based knowledge of recurring chromosome rearrangements, in particular translocations and inversions, has resulted in significant advances in understanding the molecular pathogenesis of leukaemia. Identification of a number of unique fusion genes has facilitated the development of highly specific small interfering RNAs (siRNA). Although delivery of siRNA using multifunctional nanoparticles has been investigated to treat solid cancers, the application of this approach to blood cancers is at an early stage. This review describes current treatments for leukaemia and highlights the potential of leukaemic fusion genes as therapeutic targets for RNA interference (RNAi). In addition, the design of biomimetic nanoparticles which are capable of responding to the physiological environment of leukaemia and their potential to advance RNAi therapeutics to the clinic will be critically evaluated. PMID:25218571

Guo, Jianfeng; Cahill, Mary R; McKenna, Sharon L; O'Driscoll, Caitriona M

2014-12-01

106

Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles  

NASA Astrophysics Data System (ADS)

The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon resonance, was measured during laser application. Successful release of doxorubicin via laser application was measured with fluorescence measurements providing proof that the doxorubicin was successfully intercalated and released.

Brann, Tyler

107

Successful treatment of photo-damaged skin of nano-scale atRA particles using a novel transdermal delivery  

Microsoft Academic Search

We show a novel drug delivery system (DDS) for improved all-trans retinoic acid (atRA) therapy for external treatments of photo-damaged skin. We prepared inorganic-coated atRA nanoparticles, in turn an egg-like structure in nano-scale (Nano-atRA), using boundary-organized reaction droplets. The interfacial properties of organic architectures, in atRA micelles, were used to template the nucleation of inorganic minerals. As a result, irritation

Yoko Yamaguchi; Teruaki Nagasawa; Natsumi Nakamura; Mitsuko Takenaga; Masako Mizoguchi; Shin-ichi Kawai; Yutaka Mizushima; Rie Igarashi

2005-01-01

108

Design, Fabrication and Analysis of Silicon Hollow Microneedles for Transdermal Drug Delivery System for Treatment of Hemodynamic Dysfunctions  

Microsoft Academic Search

In this paper, we present design, fabrication and coupled multifield analysis of hollow out-of-plane silicon microneedles\\u000a with piezoelectrically actuated microfluidic device for transdermal drug delivery (TDD) system for treatment of cardiovascular\\u000a or hemodynamic disorders such as hypertension. The mask layout design and fabrication process of silicon microneedles and\\u000a reservoir involving deep reactive ion etching (DRIE) is first presented. This is

M. W. Ashraf; S. Tayyaba; A. Nisar; N. Afzulpurkar; D. W. Bodhale; T. Lomas; A. Poyai; A. Tuantranont

2010-01-01

109

Tolerability of Two Sequential Electroporation Treatments Using MedPulser DNA Delivery System (DDS) in Healthy Adults  

Microsoft Academic Search

Immunotherapy against infectious agents and malignant tumors requires efficient priming of effector cells through direct expression and\\/or efficient cross-presentation of antigens by antigen-presenting cells. Electroporation is a new procedure aimed at transiently increasing cell membrane permeability and direct delivery of antigen or antigen-encoding nucleic acids inside targeted cells. We evaluated the tolerability including compliance with repeated electroporation treatments using MedPulser

Mark Wallace; Barbara Evans; Sandra Woods; Robin Mogg; Lei Zhang; Adam C Finnefrock; Dietmar Rabussay; Michael Fons; John Mallee; Devan Mehrotra; Florian Schödel; Luwy Musey

2009-01-01

110

Treatment planning system and dose delivery accuracy in extracranial stereotactic radiotherapy using Elekta body frame  

NASA Astrophysics Data System (ADS)

The purpose of this study was to measure the photon beam transmission through the Elekta Stereotactic Body Frame (ESBF) and treatment couch, to determine the dose calculations accuracy of the MasterPlan Treatment Planning System (TPS) using Pencil Beam (PBA) and Collapsed Cone (CCA) algorithms during the use of Elekta Stereotactic Body Frame (ESBF), and to demonstrate a simple calculation method to put this transmission into account during the treatment planning dose calculations. The dose was measured at the center of an in-house custom-built inhomogeneous PMMA thorax phantom with and without ‘the frame + treatment couch’. The phantom was CT-imaged inside the ESBF and planned with multiple 3D-CRT fields using PBA and CCA for photon beams of energies 6 MV and 10 MV. There were two treatment plans for dose calculations. In the first plan, the ‘frame + couch’ were included in the body contour and, therefore, included in the TPS dose calculations. In the second plan, the ‘frame + couch’ were not included in the body contour and, therefore, not included in the calculations. Transmission of the ‘frame + couch’ was determined by the ratio of the dose measurements with the ‘frame + couch’ to the measurements without them. To validate the accuracy of the calculation model, plans with and without the ‘frame + couch’ surrounding the phantoms were compared with their corresponding measurements. The transmission of the ‘frame + couch’ varies from 90.23-97.54% depending on the energy, field size, the angle of the beams and whether the beams also intercept them. The validation accuracy of the Pencil Beam (PBA) and Collapsed Cone (CCA) algorithms were within 5.33% and 4.04% respectively for the individual measurements for all gantry angles under this study. The results showed that both PBA and CCA algorithms can calculate the dose to the target within 4.25% and 1.95% of the average measured value. The attenuation caused by the ESBF and couch must be accounted into the planning process. For MasterPlan, the ‘frame + couch’ should be contoured and included in all calculations. This can be done easily and accurately.

Dawod, Tamer; Bremer, Michael; Karstens, Johann H.; Werner, Martin

2010-01-01

111

Articulating feedstock delivery device  

DOEpatents

A fully articulable feedstock delivery device that is designed to operate at pressure and temperature extremes. The device incorporates an articulating ball assembly which allows for more accurate delivery of the feedstock to a target location. The device is suitable for a variety of applications including, but not limited to, delivery of feedstock to a high-pressure reaction chamber or process zone.

Jordan, Kevin

2013-11-05

112

Catheter displacement prior to the delivery of high-dose-rate brachytherapy in the treatment of prostate cancer patients  

PubMed Central

Purpose The purpose of this work was to report measured catheter displacement prior to the delivery of high-dose-rate brachytherapy (HDR) in the treatment of prostate cancer. Material and methods Data from 30 prostate cancer patients treated with HDR brachytherapy were analyzed retrospectively. Eighteen transperineal hollow catheters were inserted under transrectal ultrasound guidance. Gold marker seeds were also placed transperineally into the base and apex of the prostate gland. Five treatment fractions of 7.5 Gy each were administered over 3 days. The patient underwent CT scanning prior to each treatment fraction. Catheter displacement was measured from the pre-treatment CT dataset reconstructed at 1.25 mm slice thickness. Results Most of catheters were displaced in the caudal direction. Variations of 18 catheters for each patient were small (standard deviations < 1 mm for all but one patient). Mean displacements relative to the apex marker were 6 ± 4 mm, 12 ± 6 mm, 12 ± 6 mm, 12 ± 6 mm, and 12 ± 6 mm from plan to 1st, 2nd, 3rd, 4th, and 5th fractions, respectively. Conclusions Our results indicate that catheter positions must be confirmed and if required, adjusted, prior to every treatment fraction for the precise treatment delivery of HDR brachytherapy, and to potentially reduce over-dosage to the bulbo-membranous urethra. PMID:25097556

Kawakami, Shogo; Terazaki, Tsuyoshi; Soda, Itaru; Satoh, Takefumi; Kitano, Masashi; Kurosaka, Shinji; Sekiguchi, Akane; Komori, Shouko; Iwamura, Masatsugu; Hayakawa, Kazushige

2014-01-01

113

Novel thermosensitive pentablock copolymers for sustained delivery of proteins in the treatment of posterior segment diseases.  

PubMed

Biodegradable and injectable in situ thermosensitive hydrogels were investigated for sustained delivery of pro- tein therapeutics in the treatment of ocular posterior segment neovascular diseases. A series of triblock (TB, polycaprolac- tone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL), B-A-B) and pentablock copolymers (PBCs) (polylactic acid (PLA)-PCL-PEG-PCL-PLA (C-B-A-B-C) and PEG-PCL-PLA-PCL-PEG (A-B-C-B-A)) were synthesized and evaluated for their thermosensitive behavior. Effects of molecular weight, hydr ophobicity and block arrangement on polymer crys-tallinity, sol-gel transition, micelle size, viscosity and in vitro drug release were examined. Results from sol-gel transition studies demonstrated that aqueous solutions of block copolymers can immediately transform to hydrogel upon exposure to physiological temperature. PBC provide significantly longer sustained release (more than 20 days) of IgG relative to TB copolymers. Moreover, kinematic viscosity of aqueous solution at 25°C for A-B-C-B-A type of PBCs was noticeably lower than the TB (B-A-B) copolymers and other PBCs with C-B-A-B-C block arrangements suggesting desired syringe- ability. The presence of PLA blocks in PBCs (C-B-A-B-C and A-B-C-B-A) significantly reduces crystallinity. Hence, it is anticipated that PBCs will have a faster rate of degradation relative to PCL-PEG-PCL based TB c opolyme rs. PBCs also exhibited excellent cell viability and biocompatibility on ARPE-19 (human retinal pigment epithelial cell line) and RAW- 264.7 (mouse macrophage cells), likely rendering it safe for ocular applications. Owing to biodegradability, thermosensi- tivity, ease of handling and biocompatibility PBC hydrogels can be considered as promising biomaterial for sustained de- livery of protein therapeutics to the back of the eye. PMID:25315374

Patel, Sulabh P; Vaishya, Ravi; Yang, Xiaoyan; Pal, Dhananjay; Mitra, Ashim K

2014-01-01

114

Ophthalmic delivery of sparfloxacin from in situ gel formulation for treatment of experimentally induced bacterial keratitis.  

PubMed

The objective of the present work was (1) to develop an in situ gelling ophthalmic delivery system by combining pluronic F127 and pluronic F68, with sparfloxacin; and (2) to examine the influence of incorporating a mucoadhesive polysaccharide such as sodium hyaluronate on the healing property due to bacterial keratitis. The formulations (F1-F6) were sterilized by gamma irradiated using Co(60) . Ultraviolet (UV) and infrared (IR) spectra studies were performed on sterilized and non-sterilized formulae. The formulations were evaluated for rheological characteristics, in vitro release behavior, and efficacy against induced bacterial conjunctivitis in rats' eyes. Moreover, histopathological evaluations were also done. All the samples passed sterility tests, and no change in physical appearance of the formulae due to gamma radiation was observed. The IR spectra of the formulae before and after sterilization showed similar peaks which confirmed that no ingredient was affected by gamma radiation. The formulations showed a flow index of 0.116-0.493 indicating pseudoplastic flow behavior. The release behavior of all formulae was non-Fickian anomalous release. The different formulae used to overcome the pathological alterations, produced by bacteria infections varied among each other depending on the duration of treatment; however, the effectiveness of formulation was arranged as F5, F4 and F3, respectively. The developed formulations were therapeutically efficacious, and provided sustained release of the drug over a 24-hour period. A better improvement in artificially induced bacterial conjunctivitis in rats' cornea was observed with the developed formulae; thus it can be considered as a viable alternative to conventional eye drops. PMID:21322120

Nesseem, Demiana I

2011-02-01

115

Chronomodulated drug delivery system of urapidil for the treatment of hypertension  

PubMed Central

Introduction: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. Materials and methods: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. Results: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. Conclusions: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension.

Chaudhary, Sona S.; Patel, Hetal K.; Parejiya, Punit B.; Shelat, Pragna K.

2015-01-01

116

Pectin Matrix as Oral Drug Delivery Vehicle for Colon Cancer Treatment  

Microsoft Academic Search

Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided\\u000a by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic\\u000a agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected\\u000a to increase drug bioavailability at

Tin Wui Wong; Gaia Colombo; Fabio Sonvico

2011-01-01

117

In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment.  

PubMed

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

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

2014-01-01

118

Efficacy of intracerebral delivery of cisplatin in combination with photon irradiation for treatment of brain tumors  

PubMed Central

We have evaluated the efficacy of intracerebral (i.c.) convection-enhanced delivery (CED) of cisplatin in combination with photon irradiation for the treatment of F98 glioma-bearing rats. One thousand glioma cells were stereotactically implanted into the brains of Fischer rats and 13 days later cisplatin (6?g/20?L) was administered i.c. by CED at a flow rate of 0.5?L/min. On the following day the animals were irradiated with a single 15 Gy dose of X-rays, administered by a linear accelerator (LINAC) or 78.8 keV synchrotron X-rays at the European Synchrotron Radiation Facility (ESRF). Untreated controls had a mean survival time (MST) ± standard error of 24 ± 1 d. compared to > 59 ± 13 d. for rats that received cisplatin alone with 13% of the latter surviving >200 d. Rats that received cisplatin in combination with either 6 MV (LINAC) or 78.8 keV (synchrotron) X-rays had almost identical MSTs of > 75±18 d. and > 74±19 d., respectively with 17% and 18% long term survivors. Microscopic examination of the brains of long term surviving rats revealed an absence of viable tumor cells and cystic areas at the presumptive site of the tumor. Our data demonstrate that i.c. CED of cisplatin in combination with external X-irradiation significantly enhanced the survival of F98 glioma-bearing rats. This was independent of the X-ray beam energy and probably was not due to the production of Auger electrons as we previously had postulated. Our data provide strong support for the approach of concomitantly administering platinum based chemotherapy in combination with radiotherapy for the treatment of brain tumors. Since a conventional LINAC can be used as the radiation source, this should significantly broaden the clinical applicability of this approach compared to synchrotron radiotherapy, which could only be carried out at a very small number of specialized facilities. PMID:20012464

Rousseau, Julia; Barth, Rolf F.; Fernandez, Manuel; Adam, Jean-François; Balosso, Jacques; Estève, François; Elleaume, Hélène

2010-01-01

119

Treatment of recurrent glioblastoma: can local delivery of mitoxantrone improve survival?  

PubMed

In this study, the records of 276 adult patients with recurrent glioblastoma (GBM) treated at recurrence at our institution between 2004 and 2006 were reviewed for progression-free survival (PFS), overall survival (OS), and toxicity. At recurrence, all patients underwent systemic treatment with temozolomide (200 mg/sqm on days 1-5 every 28 days) until tumor progression. Patients, whose tumor was judged resectable without risk of adjunctive neurological deficit, underwent a second surgery with or without positioning of a Rickam/Ommaya reservoir. The reservoir was used for locoregional chemotherapy with mitoxantrone. Two hundred seventy-six rGBL patients (pts) were divided into three subgroups: A 161 pts treated only with temozolomide, B 50 pts re-operated-on +temozolomide, and C 65 pts re-operated on + temozolomide + locoregional CHT. For group A, the 6 month PFS and 6 month survival (ST) were 39.3 and 43%, respectively, with a median survival time (mST) of 5 months (range 4-6) and 25% of pts alive at 9 months. For group B, the 6 month PFS and 6 month survivors were 64 and 74.1%, respectively, with a mST of 8 months (range 6-10) and 25% of pts alive at 12 months. For group C, the 6 month PFS and 6 month survivors were 70.7 and 87.7%, respectively, with a mST of 11 months (range 9-13) and 25% of pts alive at 18 months (A vs. B vs. C, log-rank P < 0.001) (B vs. C, P = 0.041) (A vs. B P = 0.009). Cox proportional hazard model was used to obtain Hazard Ratio (HR) for type of treatment corrected by age and time (in months) between diagnosis and first recurrence: second tumor debulking was statistically effective for survival, reducing by 36% the risk of death (HR = 0.64; 0.46-0.89), but the most significant favorable prognostic factor for survival was the local delivery of mitoxantrone which reduced the risk of death to 50% (HR = 0.50; 0.38-0.68). PMID:18283418

Boiardi, Amerigo; Silvani, Antonio; Eoli, Marica; Lamperti, Elena; Salmaggi, Andrea; Gaviani, Paola; Fiumani, Anna; Botturi, Andrea; Falcone, Chiara; Solari, Alessandra; Filippini, Graziella; Di Meco, Francesco; Broggi, Giovanni

2008-05-01

120

Penetration depth, concentration and efficiency of transdermal ?-arbutin delivery after ultrasound treatment with albumin-shelled microbubbles in mice.  

PubMed

Abstract Recently, the feasibility and effects of using microbubbles (MBs) as an ultrasound (US) contrast agent for enhancing the penetration in transdermal delivery in vivo have been demonstrated, but the mechanism and efficiency are unclear. This study demonstrates the penetration depth, concentration and efficiency of transdermal ?-arbutin delivery during 4 weeks after US treatment with MBs in mice. Experimental animals were randomly divided into the following four groups (n?=?5 animals per group): (1) penetrating ?-arbutin alone (C), (2) US combined with penetrating ?-arbutin, (3) US combined with MBs and penetrating ?-arbutin, and (4) US combined with diluted MBs and penetrating ?-arbutin (UBD). The penetration depths in agarose phantoms and pigskin were 47 and 84% greater for group UBD, respectively, than for group C. The in vitro skin penetration by 2% ?-arbutin after 3?h was 83% greater in group UBD than in group C. The degree of in vivo skin whitening (quantified as the luminosity index) in group UBD significantly increased by 25% after 1 week, 34% after 2 weeks, and then stabilized after 3 weeks at 37% in C57BL/6J mice over a 4-week experimental period. Our results indicate that combined treatment with optimal US and MBs can increase skin permeability so as to enhance ?-arbutin delivery to inhibit melanogenesis without damaging the skin in mice. PMID:25148541

Liao, Ai-Ho; Ma, Wan-Chun; Wang, Chih-Hung; Yeh, Ming-Kung

2014-08-22

121

Investigating the Temporal Effects of Respiratory-Gated and Intensity-Modulated Radiotherapy Treatment Delivery on In Vitro Survival: An Experimental and Theoretical Study  

SciTech Connect

Purpose: To experimentally and theoretically investigate the temporal effects of respiratory-gated and intensity-modulated radiotherapy (IMRT) treatment delivery on in vitro survival. Methods and Materials: Experiments were designed to isolate the effects of periodic irradiation (gating), partial tumor irradiation (IMRT), and extended treatment time (gating and IMRT). V79 Chinese hamster lung fibroblast cells were irradiated to 2 Gy with four delivery methods and a clonogenic assay performed. Theoretical incomplete repair model calculations were performed using the incomplete repair model. Results: Treatment times ranged from 1.67 min (conformal radiotherapy, CRT) to 15 min (gated IMRT). Survival fraction calculations ranged from 68.2% for CRT to 68.7% for gated IMRT. For the same treatment time (5 min), gated delivery alone and IMRT delivery alone both had a calculated survival fraction of 68.3%. The experimental values ranged from 65.7% {+-} 1.0% to 67.3% {+-} 1.3%, indicating no significant difference between the experimental observations and theoretical calculations. Conclusion: The theoretical results predicted that of the three temporal effects of radiation delivery caused by gating and IMRT, extended treatment time was the dominant effect. Care should be taken clinically to ensure that the use of gated IMRT does not significantly increase treatment times, by evaluating appropriate respiratory gating duty cycles and IMRT delivery complexity.

Keall, Paul J. [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: Paul.Keall@stanford.edu; Chang, Michael [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Benedict, Stanley [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Thames, Howard [Department of Biomathematics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Vedam, S. Sastry [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Lin, Peck-Sun [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)

2008-08-01

122

Preparation and characterization of novel carbopol based bigels for topical delivery of metronidazole for the treatment of bacterial vaginosis.  

PubMed

The current study reports the development of bigels using sorbitan monostearate-sesame oil organogel and carbopol 934 hydrogel. The microstructures and physicochemical properties were investigated by microscopy, viscosity measurement, mechanical analysis and differential scanning calorimetry analysis. Fluorescence microscopy confirmed the formation of oil-in-water type of emulsion gel. There was an increase in the strength of the bigels as the proportion of the organogel was increased in the bigels. The developed bigels showed shear-thinning flow behavior. The stress relaxation study suggested viscoelastic nature of the bigels. The developed bigels were biocompatible. Metronidazole, drug of choice for the treatment of bacterial vaginosis, loaded bigels showed diffusion-mediated drug release. The drug loaded gels showed good antimicrobial efficiency against Escherichia coli. In gist, the developed bigels may be used as delivery vehicles for the vaginal delivery of the drugs. PMID:25280691

Singh, Vinay K; Anis, Arfat; Banerjee, Indranil; Pramanik, Krishna; Bhattacharya, Mrinal K; Pal, Kunal

2014-11-01

123

Drug delivery system design and development for boron neutron capture therapy on cancer treatment.  

PubMed

We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,l-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. PMID:24447933

Sherlock Huang, Lin-Chiang; Hsieh, Wen-Yuan; Chen, Jiun-Yu; Huang, Su-Chin; Chen, Jen-Kun; Hsu, Ming-Hua

2014-06-01

124

Closed-loop insulin delivery for treatment of type 1 diabetes  

PubMed Central

Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence, and remains a serious chronic disorder with increased morbidity and mortality, and reduced quality of life. Technological innovations positively affect the management of type 1 diabetes. Closed-loop insulin delivery (artificial pancreas) is a recent medical innovation, aiming to reduce the risk of hypoglycemia while achieving tight control of glucose. Characterized by real-time glucose-responsive insulin administration, closed-loop systems combine glucose-sensing and insulin-delivery components. In the most viable and researched configuration, a disposable sensor measures interstitial glucose levels, which are fed into a control algorithm controlling delivery of a rapid-acting insulin analog into the subcutaneous tissue by an insulin pump. Research progress builds on an increasing use of insulin pumps and availability of glucose monitors. We review the current status of insulin delivery, focusing on clinical evaluations of closed-loop systems. Future goals are outlined, and benefits and limitations of closed-loop therapy contrasted. The clinical utility of these systems is constrained by inaccuracies in glucose sensing, inter- and intra-patient variability, and delays due to absorption of insulin from the subcutaneous tissue, all of which are being gradually addressed. PMID:22071283

2011-01-01

125

Functional Analysis and Treatment of Rumination Using Fixed-Time Delivery of a Flavor Spray  

ERIC Educational Resources Information Center

A functional analysis suggested that rumination exhibited by an adult with autism was maintained by automatic reinforcement. Next, a preference assessment with three flavor sprays (i.e., flavored sprays used by dieters) showed that apple pie spray was most preferred. Finally, the effects of fixed-time delivery of the apple pie spray on levels of…

Wilder, David A.; Register, Martisa; Register, Stanley; Bajagic, Vedrana; Neidert, Pamela L.

2009-01-01

126

Investigation of Pitch and Jaw Width to Decrease Delivery Time of Helical Tomotherapy Treatments for Head and Neck Cancer  

SciTech Connect

Helical tomotherapy plans using a combination of pitch and jaw width settings were developed for 3 patients previously treated for head and neck cancer. Three jaw widths (5, 2.5, and 1 cm) and 4 pitches (0.86, 0.43, 0.287, and 0.215) were used with a (maximum) modulation factor setting of 4. Twelve plans were generated for each patient using an identical optimization procedure (e.g., number of iterations, objective weights, and penalties, etc.), based on recommendations from TomoTherapy (Madison, WI). The plans were compared using isodose plots, dose volume histograms, dose homogeneity indexes, conformity indexes, radiobiological models, and treatment times. Smaller pitches and jaw widths showed better target dose homogeneity and sparing of normal tissue, as expected. However, the treatment time increased inversely proportional to the jaw width, resulting in delivery times of 24 {+-} 1.9 min for the 1-cm jaw width. Although treatment plans produced with the 2.5-cm jaw were dosimetrically superior to plans produced with the 5-cm jaw, subsequent calculations of tumor control probabilities and normal tissue complication probabilities suggest that these differences may not be radiobiologically meaningful. Because treatment plans produced with the 5-cm jaw can be delivered in approximately half the time of plans produced with the 2.5-cm jaw (5.1 {+-} 0.6 min vs. 9.5 {+-} 1.1 min), use of the 5-cm jaw in routine treatment planning may be a viable approach to decreasing treatment delivery times from helical tomotherapy units.

Moldovan, Monica [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Fontenot, Jonas D., E-mail: jfontenot@marybird.com [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Gibbons, John P. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States); Lee, Tae Kyu [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Rosen, Isaac I. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States); Fields, Robert S. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Hogstrom, Kenneth R. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States)

2011-01-01

127

Prostate intrafraction motion evaluation using kV fluoroscopy during treatment delivery: A feasibility and accuracy study  

SciTech Connect

Margin reduction for prostate radiotherapy is limited by uncertainty in prostate localization during treatment. We investigated the feasibility and accuracy of measuring prostate intrafraction motion using kV fluoroscopy performed simultaneously with radiotherapy. Three gold coils used for target localization were implanted into the patient's prostate gland before undergoing hypofractionated online image-guided step-and-shoot intensity modulated radiation therapy (IMRT) on an Elekta Synergy linear accelerator. At each fraction, the patient was aligned using a cone-beam computed tomography (CBCT), after which the IMRT treatment delivery and fluoroscopy were performed simultaneously. In addition, a post-treatment CBCT was acquired with the patient still on the table. To measure the intrafraction motion, we developed an algorithm to register the fluoroscopy images to a reference image derived from the post-treatment CBCT, and we estimated coil motion in three-dimensional (3D) space by combining information from registrations at different gantry angles. We also detected the MV beam turning on and off using MV scatter incident in the same fluoroscopy images, and used this information to synchronize our intrafraction evaluation with the treatment delivery. In addition, we assessed the following: the method to synchronize with treatment delivery, the dose from kV imaging, the accuracy of the localization, and the error propagated into the 3D localization from motion between fluoroscopy acquisitions. With 0.16 mAs/frame and a bowtie filter implemented, the coils could be localized with the gantry at both 0 deg. and 270 deg. with the MV beam off, and at 270 deg. with the MV beam on when multiple fluoroscopy frames were averaged. The localization in two-dimensions for phantom and patient measurements was performed with submillimeter accuracy. After backprojection into 3D the patient localization error was (-0.04{+-}0.30) mm, (0.09{+-}0.36) mm, and (0.03{+-}0.68) mm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) axes, respectively. Simulations showed that while oscillating (stationary) motion cannot be effectively represented in 3D, linearly drifting (nonstationary) motion is detectable with good accuracy. These results show that measuring prostate intrafraction motion using a single kV imager during radiotherapy is feasible and can be performed with acceptable accuracy.

Adamson, Justus; Wu Qiuwen [Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48201 and Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073 (United States); Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073 (United States)

2008-05-15

128

Exploring barriers to the delivery of cervical cancer screening and early treatment services in Malawi: some views from service providers  

PubMed Central

Background Cervical cancer is the most common reproductive health cancer in Malawi. In most cases, women report to health facilities when the disease is in its advanced stage. In this study, we investigate service providers’ perceptions about barriers for women to access cervical cancer screening and early treatment services in Malawi. Methods We conducted in-depth interviews with 13 district coordinators and 40 service providers of cervical cancer screening and early treatment services in 13 districts in Malawi. The study was conducted in 2012. The district coordinators helped the research team identify the health facilities which were providing cervical cancer screening and early treatment services. Results Almost all informants reported that cervical cancer was a major public health problem in their districts and that prevention efforts for this disease were being implemented. They were aware of the test and treat approach using visual inspection with acetic acid (VIA). They, however, said that the delivery of cervical cancer screening and early treatment services was compromised because of factors such as gross shortage of staff, lack of equipment and supplies, the lack of supportive supervision, and the use of male service providers. Informants added that the lack of awareness about the disease among community members, long distances to health facilities, the lack of involvement of husbands, and prevailing misperceptions about the disease (eg, that it is caused by the exposure to the VIA process) affect the uptake of these services. Conclusion While progress has been made in the provision of cervical cancer screening and early treatment services in Malawi, a number of factors affect service delivery and uptake. There is a need to continue creating awareness among community members including husbands and also addressing identified barriers such as shortage of staff and supplies in order to improve uptake of services.

Munthali, Alister C; Ngwira, Bagrey M; Taulo, Frank

2015-01-01

129

Nanomedicine: making controllable magnetic drug delivery possible for the treatment of breast cancer  

Microsoft Academic Search

A recent study published in Nano Letters documents the synthesis and performance of porous silica nanocapsules filled with magnetic nanoparticles as a controllable\\u000a magnetic drug delivery vector. Under a remotely applied radiofrequency magnetic field, these nanocapsules demonstrate on-off\\u000a switchable release of the internally loaded drug payload. Both in vitro and in vivo studies using MT2 mouse breast cancer cell models

Lesa A Tran; Lon J Wilson

2011-01-01

130

Chitosan and Glyceryl Monooleate Nanostructures Containing Gemcitabine: Potential Delivery System for Pancreatic Cancer Treatment  

Microsoft Academic Search

The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan\\/glyceryl monooleate (GMO) nanostructures,\\u000a and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size,\\u000a and surface charge were determined by atomic force microscopy (AFM), and a

William J. Trickler; Jatin Khurana; Ankita A. Nagvekar; Alekha K. Dash

2010-01-01

131

Sub-micrometric liposomes as drug delivery systems in the treatment of periodontitis.  

PubMed

Periodontitis is a complex disease and bacterial infection is one of the most common factors involved in this disease. Current strategies for the local delivery of antibiotics do not allow a complete clearance of bacteria filling dentinal tubules and this limits their therapeutic efficacy. Therefore, there is a strong need for the development of new delivery strategies aimed at improving the efficacy of antibiotic therapy for periodontitis with special reference to their ability to penetrate into the tubules. The aim of the present study is to develop liposome-based delivery systems of sub-micron dimension, able to diffuse into the dentinal tubules. A further aim of the research is to develop a protocol for enhanced diffusion based on the use of magnetic liposomes and magnetic fields. Liposomes were produced by hydration of a pre-liposomal formulation. The vesicles were stabilised with PEG and their re-sizing was achieved by extrusion. Magnetite nanoparticles were synthesized inside the vesicles, i.e., the chemical reaction involving FeCl?, FeCl? and NH? occurred within the core of the newly formed liposomes. Dynamic light scattering analysis was performed for size characterization. A mathematical model was implemented to predict the diffusion of the liposomes in dentinal tubules. Ex-vivo validation was performed on extracted human teeth. We produced PEG-ylated liposomes (average size 204.3 nm) and PEG-ylated magnetic liposomes (average size 286 nm) and an iron content of 4.2 ?g/ml. Through mathematical modelling, we deduced that sub-micrometer vesicles are able to penetrate into dentinal tubules. This penetration is considerably more effective when the vesicles are magnetized and subjected to an external magnetic field which accelerates their movement within the tubules. The liposome-based delivery systems developed by the present study are able to penetrate deeply into the tubules, sometimes reaching their terminal ends. PMID:23058016

Di Turi, G; Riggio, C; Vittorio, O; Marconcini, S; Briguglio, F; Funel, N; Campani, D; Barone, A; Raffa, V; Covani, U

2012-01-01

132

Topical delivery of therapeutic agents in the treatment of inflammatory bowel disease  

Microsoft Academic Search

For targeting local and systemic inflammatory processes in inflammatory bowel disease (IBD) therapeutic agents of first choice (e.g. aminosalicylates, corticosteroids) have been developed in special galenic forms to accomplish the topical delivery of the active compounds to the terminal ileum (Crohn's disease) and\\/or the colon (Crohn's disease and ulcerative colitis). However, it has to be realized that intestinal physiology (e.g.

Ulrich Klotz; Matthias Schwab

2005-01-01

133

Paclitaxel and Gemcitabine Combinational Drug-loaded Mucoadhesive Delivery System in the Treatment of Colon Cancers.  

PubMed

The combination of two different types of chemo-therapeutic drugs via nanocarriers is emerged as a promising strategy for treating multiple cancers. Such a co-delivery system will synchronize the drug exposure and synergize the therapeutic effects. Herein, we prepared a paclitaxel (PTX) and gemcitabine (GEM)-loaded N-succinyl chitosan nanoparticles (NSC NP) to target colon cancer. NSC NP showed a pH sensitive swelling at colonic pH and exhibited a sequential release pattern for both the drugs. Binary drug combination exhibited a synergistic cytotoxicity against HT-29 colon cancer cells with a remarkable G2/M phase arrest. Specifically, in vivo antitumor efficacy study showed that NSC NP prolonged the survival time of tumor-bearing mice up to 45 days wherein 50% of mice were still alive. Therefore, these results suggest that co-delivery of drugs with a suitable delivery system could potentially improve the therapeutic efficacy in colon cancers. The study can be further continued by using different types of chemotherapeutic drugs that targets different molecular targets using pH-sensitive nanocarriers. PMID:24941086

Guo, X-Y; Wang, P; Du, Q-G; Han, S; Zhu, S-M; Lv, Y-F; Liu, G-S; Hao, Z-M

2015-04-01

134

Pulmonary Delivery of an Ultra-Fine Oxytocin Dry Powder Formulation: Potential for Treatment of Postpartum Haemorrhage in Developing Countries  

PubMed Central

Oxytocin is recommended by the World Health Organisation as the most effective uterotonic for the prevention and treatment of postpartum haemorrhage. The requirement for parenteral administration by trained healthcare providers and the need for the drug solution to be maintained under cold-chain storage limit the use of oxytocin in the developing world. In this study, a spray-dried ultrafine formulation of oxytocin was developed with an optimal particle size diameter (1-5 µm) to facilitate aerosolised delivery via the lungs. A powder formulation of oxytocin, using mannitol, glycine and leucine as carriers, was prepared with a volume-based median particle diameter of 1.9 µm. Oxytocin content in the formulation was assayed using high-performance liquid chromatography-mass spectroscopy and was found to be unchanged after spray-drying. Ex vivo contractility studies utilising human and ovine uterine tissue indicated no difference in the bioactivity of oxytocin before and after spray-drying. Uterine electromyographic (EMG) activity in postpartum ewes following pulmonary (in vivo) administration of oxytocin closely mimicked that observed immediately postpartum (0-12 h following normal vaginal delivery of the lamb). In comparison to the intramuscular injection, pulmonary administration of an oxytocin dry powder formulation to postpartum ewes resulted in generally similar EMG responses, however a more rapid onset of uterine EMG activity was observed following pulmonary administration (129 ± 18 s) than intramuscular injection (275 ± 22 s). This is the first study to demonstrate the potential for oxytocin to elicit uterine activity after systemic absorption as an aerosolised powder from the lungs. Aerosolised oxytocin has the potential to provide a stable and easy to administer delivery system for effective prevention and treatment of postpartum haemorrhage in resource-poor settings in the developing world. PMID:24376618

Ibrahim, Jibriil P.; Bischof, Robert J.; Nassta, Gemma C.; Olerile, Livesey D.; Russell, Adrian S.; Meiser, Felix; Parkington, Helena C.; Coleman, Harold A.; Morton, David A. V.; McIntosh, Michelle P.

2013-01-01

135

Probenecid treatment enhances retinal and brain delivery of N-4-benzoylaminophenylsulfonylglycine: an anionic aldose reductase inhibitor.  

PubMed

Anion efflux transporters are expected to minimize target tissue delivery of N-[4-(benzoylaminophenyl)sulfonyl]glycine (BAPSG), a novel carboxylic acid aldose reductase inhibitor, which exists as a monocarboxylate anion at physiological conditions. Therefore, the objective of this study was to determine whether BAPSG delivery to various eye tissues including the retina and the brain can be enhanced by probenecid, a competitive inhibitor of anion transporters. To determine the influence of probenecid on eye and brain distribution of BAPSG, probenecid was administered intraperitoneally (120 mg/kg body weight; i.p.) 20 min prior to BAPSG (50 mg/kg; i.p.) administration. Drug disposition in various eye tissues including the retina and the brain was determined at 15 min, 1, 2 and 4h after BAPSG dose in male Sprauge-Dawley rats. To determine whether probenecid alters plasma clearance of BAPSG, influence of probenecid (120 mg/kg; i.p.) on the plasma pharmacokinetics of intravenously administered BAPSG (15 mg/kg) was studied as well. Finally, the effect of probenecid co-administration on the ocular tissue distribution of BAPSG was assessed in rabbits following topical (eye drop) administration. Following pretreatment with probenecid in the rat study, retinal delivery at 1h was increased by about 11-fold (2580 ng/g vs. 244 ng/g; p<0.05). Further, following probenecid pretreatment, significant BAPSG levels were detectable in the brain (45 + or - 20 ng/g) at 1h, unlike controls where the drug was not detectable. Plasma concentrations, plasma elimination half-life, and total body clearance of intravenously administered BAPSG were not altered by i.p. probenecid pretreatment. In the topical dosing study, a significant decline in BAPSG delivery was observed in the iris-ciliary body but no significant changes were observed in other tissues of the anterior segment of the eye including tears. Thus, inhibition of anion transporters is a useful approach to elevate retinal and brain delivery of BAPSG. PMID:19761819

Sunkara, Gangadhar; Ayalasomayajula, Surya P; DeRuiter, Jack; Kompella, Uday B

2010-02-15

136

Telodendrimer nanocarrier for co-delivery of paclitaxel and cisplatin: A synergistic combination nanotherapy for ovarian cancer treatment.  

PubMed

Cisplatin (CDDP) and paclitaxel (PTX) are two established chemotherapeutic drugs used in combination for the treatment of many cancers, including ovarian cancer. We have recently developed a three-layered linear-dendritic telodendrimer micelles (TM) by introducing carboxylic acid groups in the adjacent layer via "thio-ene" click chemistry for CDDP complexation and conjugating cholic acids via peptide chemistry in the interior layer of telodendrimer for PTX encapsulation. We hypothesize that the co-delivery of low dosage PTX with CDDP could act synergistically to increase the treatment efficacy and reduce their toxic side effects. This design allowed us to co-deliver PTX and CDDP at various drug ratios to ovarian cancer cells. The in vitro cellular assays revealed strongest synergism in anti-tumor effects when delivered at a 1:2 PTX/CDDP loading ratio. Using the SKOV-3 ovarian cancer xenograft mouse model, we demonstrate that our co-encapsulation approach resulted in an efficient tumor-targeted drug delivery, decreased cytotoxic effects and stronger anti-tumor effect, when compared with free drug combination or the single loading TM formulations. PMID:25453973

Cai, Liqiong; Xu, Gaofei; Shi, Changying; Guo, Dandan; Wang, Xu; Luo, Juntao

2015-01-01

137

Antenatal care visit attendance, intermittent preventive treatment during pregnancy (IPTp) and malaria parasitaemia at delivery  

PubMed Central

Background The determinants and barriers for delivery and uptake of IPTp vary with different regions in sub-Saharan Africa. This study evaluated the determinants of ANC clinic attendance and IPTp-SP uptake among parturient women from Mount Cameroon Area and hypothesized that time of first ANC clinic attendance could influence uptake of IPTp-SP/dosage and consequently malaria parasite infection status at delivery. Methods Two cross sectional surveys were carried out at the Government Medical Centre in the Mutengene Health Area, Mt Cameroon Area from March to October 2007 and June 2008 to April 2009. Consented parturient women were consecutively enrolled in both surveys. In 2007, socio-demographic data, ANC clinic attendance, gestational age, fever history and reported use/dosage of IPTp-SP were documented using a structured questionnaire. In the second survey only IPT-SP usage/dosage was recorded. Malaria parasitaemia at delivery was determined by blood smear microscopy and placental histology. Results and discussion In 2007, among the 287 women interviewed, 2.2%, 59.7%, and 38.1% enrolled in the first, second and third trimester respectively. About 90% of women received at least one dose SP but only 53% received the two doses in 2007 and by 2009 IPTp-two doses coverage increased to 64%. Early clinic attendance was associated (P?=?0.016) with fever history while being unmarried (OR?=?2.2; 95% CI: 1.3-3.8) was significantly associated with fewer clinic visits (<4visits). Women who received one SP dose (OR?=?3.7; 95% CI: 2.0-6.8) were more likely not to have attended???4visits. A higher proportion (P?delivery was frequent (P?=?0.007) among women who enrolled in the third trimester and had received only one SP dose than in those with two doses. Conclusion In the study area, late first ANC clinic enrolment and fewer clinic visits may prevent the uptake of two SP doses and education on early and regular ANC clinic visits can increase IPTp coverage. PMID:24779545

2014-01-01

138

Enhanced Topical Delivery of Tetrandrine by Ethosomes for Treatment of Arthritis  

PubMed Central

The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base (pKa = 7.06) with pH-dependent partition coefficient. The spherical-shaped ethosomes were prepared by pH gradient loading method. Ex vivo permeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund's complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin. PMID:24062995

Fan, Chao; Li, Xinru; Zhou, Yanxia; Zhao, Yong; Ma, Shujin; Li, Wenjing; Liu, Yan; Li, Guiling

2013-01-01

139

Injectable and biodegradable poly(organophosphazene) hydrogel as a delivery system of docetaxel for cancer treatment.  

PubMed

Although docetaxel (DTX) is an advanced taxoid, further augmentation of its properties is still required, such as improvement in its low aqueous solubility. Herein, we report the development of biodegradable/injectable poly(organophosphazene) (PPZ) hydrogels for the delivery of DTX without the use of organic solvents. An aqueous solution of PPZ containing ?-amino-?-methoxy-poly(ethylene glycol) (AMPEG) 750 instead of AMPEG 550 was prepared, thereby increasing the erosion capacity of the hydrogel by judicious balance of the hydrophobic/hydrophilic moieties. The safety of the hydrogel was demonstrated using a biocompatibility test. The PPZ aqueous solution (8 wt%) containing DTX exhibited a thermosensitive sol-gel-sol transition that was independent of the concentration of DTX (1-3 mg/mL). The in vitro release study indicated that the dominant release mechanism was either erosion or diffusion/erosion-controlled release depending on the DTX content of the hydrogel. The in vivo anticancer effect of the intratumorally injected PPZ system in human gastric cancer cell-xenografted mice was evaluated, which demonstrated a significantly (p < 0.01) enhanced effect of the DTX-PPZ hydrogel system compared to the control (DTX solution, i.v.). In conclusion, the PPZ hydrogel may be a promising candidate for DTX delivery, affecting a decrease in the size of tumors with little toxicity prior to exeresis. PMID:23594096

Cho, Jung-Kyo; Hong, Ji Min; Han, Taesu; Yang, Han-Kwang; Song, Soo-Chang

2013-07-01

140

Reversibly crosslinked nanocarriers for on-demand drug delivery in cancer treatment  

PubMed Central

Polymer micelles have proven to be one of the most versatile nanocarriers for anticancer drug delivery. However, the in vitro and in vivo stability of micelles remains a challenge due to the dynamic nature of these self-assembled systems, which leads to premature drug release and nonspecific biodistribution in vivo. Recently, reversibly crosslinked micelles have been developed to provide solutions to stabilize nanocarriers in blood circulation. Increased stability allows nanoparticles to accumulate at tumor sites efficiently via passive and/or active tumor targeting, while cleavage of the micelle crosslinkages, through internal or external stimuli, facilitates on-demand drug release. In this review, various crosslinking chemistries as well as the choices for reversible linkages in these nanocarriers will be introduced. Then, the development of reversibly crosslinked micelles for on-demand drug release in response to single or dual stimuli in the tumor microenvironment is discussed, for example, acidic pH, reducing microenvironment, enzymatic microenvironment, photoirradiation and the administration of competitive reagents postmicelle delivery. PMID:23323559

Shao, Yu; Huang, Wenzhe; Shi, Changying; Atkinson, Sean T; Luo, Juntao

2013-01-01

141

Capsaicin delivery into the skin with lipidic nanoparticles for the treatment of psoriasis.  

PubMed

The study aims to explore the potential of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) in improving the topical delivery of capsaicin (CAP) by in vitro and in vivo studies. The lipidic nanoparticles were prepared by solvent diffusion method and were characterized for average particle size, zeta potential and entrapment efficiency. TEM photomicrographs revealed that the particles were nanometric in size. Higher amount of CAP can be encapsulated in the NLCs (87.4 ± 3.28) as compared with SLNs (79.7 ± 2.93%). The cumulative amounts of CAP permeated through the skin and retained in the SC were higher in the case of NLCs as compared with plain drug solution and SLNs. SLNs and NLCs exhibited minimum to no irritation. All the results concluded that NLCs and SLNs have shown a good ability to increase drug accumulation in the various skin layers but NLCs may be a more potential carrier for topical delivery of CAP for an effective therapy of psoriasis. PMID:24040836

Agrawal, Udita; Gupta, Madhu; Vyas, S P

2015-02-01

142

Delivery of glutamine synthetase gene by baculovirus vectors: a proof of concept for the treatment of acute hyperammonemia.  

PubMed

Hyperammonemia, a condition present in patients with urea cycle disorders (UCDs) or liver diseases, can cause neuropsychiatric complications, which in the worst cases result in brain damage, coma or death. Diverse treatments exist for the treatment of hyperammonemia, but they have limited efficacy, adverse effects and elevated cost. Gene therapy is a promising alternative that is explored here. A baculovirus, termed Bac-GS, containing the glutamine synthetase (GS) gene was constructed for the in vitro and in vivo treatment of hyperammonemia. Transduction of MA104 epithelial or L6 myoblast/myotubes cells with Bac-GS resulted in a high expression of the GS gene, an increase in GS concentration, and a reduction of almost half of exogenously added ammonia. When Bac-GS was tested in an acute hyperammonemia rat model by intramuscularly injecting the rear legs, the concentration of ammonia in blood decreased 351??M, in comparison with controls. A high GS concentration was detected in gastrocnemius muscles from the rats transduced with Bac-GS. These results show that gene delivery for overexpressing GS in muscle tissue is a promising alternative for the treatment of hyperammonemia in patients with acute or chronic liver diseases and hepatic encephalopathy or UCD. PMID:25338921

Torres-Vega, M A; Vargas-Jerónimo, R Y; Montiel-Martínez, A G; Muñoz-Fuentes, R M; Zamorano-Carrillo, A; Pastor, A R; Palomares, L A

2015-01-01

143

Patient Satisfaction with HIV/AIDS Care and Treatment in the Decentralization of Services Delivery in Vietnam  

PubMed Central

Objective We evaluated the patient satisfaction with HIV/AIDS care and treatment and its determinants across levels of health service administration in Vietnam. Methods We interviewed 1016 patients at 7 hospitals and health centers in three epicenters, including Hanoi, Hai Phong, and Ho Chi Minh City. The Satisfaction with HIV/AIDS Treatment Interview Scale (SATIS) was developed, and 3 dimensions were constructed using factor analysis, namely “Quality and Convenience”; “Availability and Responsiveness”; and “Competence of health care workers”. Results In a band score of (0; 10), the mean scores of all domains were large; it was the highest in “Competence of health workers” (9.34±0.84), and the lowest in “Quality and Convenience” (9.03±1.04). The percentages of respondents completely satisfied with overall service quality and treatment outcomes were 42.4% and 18.8%, respectively. In multivariate analysis, factors related to higher satisfaction included female sex, older age, and living with spouses or partners. Meanwhile, lower satisfaction was found among patients who were attending provincial and district clinics; in the richest group; had higher CD4 count; and drug users. Conclusion This study highlights the importance of improving the quality of HIV/AIDS services at the provincial and district clinics. Potential strategies include capacity building for health workers, integrative service delivery, engagements of family members in treatment supports, and additional attention and comprehensive care for drug users with HIV/AIDS. PMID:23071611

Tran, Bach Xuan; Nguyen, Nhung Phuong Thi

2012-01-01

144

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94  

SciTech Connect

Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.

Fietkau, Rainer [Department of Radiation Therapy, University of Rostock, Rostock (Germany)]. E-mail: rainer.fietkau@med.uni-rostock.de; Roedel, Claus [Departments of Radiation Therapy and Surgery, University of Erlangen, Erlangen (Germany); Hohenberger, Werner [Departments of Radiation Therapy and Surgery, University of Erlangen, Erlangen (Germany); Raab, Rudolf [Department of Surgery, Klinikum Oldenburg, Oldenburg (Germany); Hess, Clemens [Departments of Radiation Therapy and General Surgery, University of Goettingen, Goettingen (Germany); Liersch, Torsten [Departments of Radiation Therapy and General Surgery, University of Goettingen, Goettingen (Germany); Becker, Heinz [Departments of Radiation Therapy and General Surgery, University of Goettingen, Goettingen (Germany); Wittekind, Christian [Institute of Pathology, University of Leipzig, Leipzig (Germany); Hutter, Matthias [Department of Radiation Therapy, Krankenhaus Nordwest Frankfurt, Frankfurt (Germany); Hager, Eva [Department of Radiation Therapy, Krankenhaus Klagenfurt, Klagenfurt (Austria); Karstens, Johann [Department of Radiation Therapy, University of Hannover, Hannover (Germany); Ewald, Hermann [Department of Radiation Therapy, University of Schleswig-Holstein, Campus Kiel, Kiel (Germany); Christen, Norbert [Department of Radiation Therapy, Krankenhaus Dresden-Friedrichstadt, Dresden (Germany); Jagoditsch, Michael [Department of Surgery, Klinikum St. Veit, St. Veit (Austria); Martus, Peter [Institute of Biostatistics and Clinical Epidemiology, Charite Universitary Medicine Berlin, Berlin (Germany); Sauer, Rolf [Departments of Radiation Therapy and Surgery, University of Erlangen, Erlangen (Germany)

2007-03-15

145

Fine-tuning vitamin e-containing telodendrimers for efficient delivery of gambogic Acid in colon cancer treatment.  

PubMed

Certain natural products such as gambogic acid (GA) exhibit potent antitumor effects. Unfortunately, administration of these natural products is limited by their poor solubility in conventional pharmaceutical solvents. In this study, a series of telodendrimers, composed of linear polyethylene glycol (PEG)-blocking-dendritic oligomer of cholic acid (CA) and vitamin E (VE), have been designed with architectures optimized for efficient delivery of GA and other natural anticancer compounds. Two of the telodendrimers with segregated CA and VE domains self-assembled into stable cylindrical and/or spherical nanoparticles (NPs) after being loaded with GA as observed under transmission electron microscopy (TEM), which correlated with the dynamic light scattering (DLS) analysis of sub-30 nm particle sizes. A very high GA loading capacity (3:10 drug/polymer w/w) and sustained drug release were achieved with the optimized telodendrimers. These novel nanoformulations of GA were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug. Near-infrared fluorescence small animal imaging revealed preferential accumulation of GA-loaded NPs into tumor tissue. The optimized nanoformulation of GA achieved superior antitumor efficacy compared to GA-Cremophor EL formulation at equivalent doses in HT-29 human colon cancer xenograft mouse models. Given the mild adverse effects associated with this natural compound and the enhanced anticancer effects via tumor targeted telodendrimer delivery, the optimized GA nanoformulation is a promising alternative to the traditional chemotherapy in colon cancer treatment. PMID:25692376

Huang, Wenzhe; Wang, Xu; Shi, Changying; Guo, Dandan; Xu, Gaofei; Wang, Lili; Bodman, Alexa; Luo, Juntao

2015-04-01

146

Systemic delivery of miR-126 by miRNA-loaded Bubble liposomes for the treatment of hindlimb ischemia  

PubMed Central

Currently, micro RNA (miRNA) is considered an attractive target for therapeutic intervention. A significant obstacle to the miRNA-based treatments is the efficient delivery of miRNA to the target tissue. We have developed polyethylene glycol-modified liposomes (Bubble liposomes (BLs)) that entrap ultrasound (US) contrast gas and can serve as both plasmid DNA (pDNA) or small interfering RNA (siRNA) carriers and US contrast agents. In this study, we investigated the usability of miRNA-loaded BLs (mi-BLs) using a hindlimb ischemia model and miR-126. It has been reported that miR-126 promotes angiogenesis via the inhibition of negative regulators of VEGF signaling. We demonstrated that mi-BLs could be detected using diagnostic US and that mi-BLs with therapeutic US could deliver miR-126 to an ischemic hindlimb, leading to the induction of angiogenic factors and the improvement of blood flow. These results suggest that combining mi-BLs with US may be useful for US imaging and miRNA delivery. PMID:24457599

Endo-Takahashi, Yoko; Negishi, Yoichi; Nakamura, Arisa; Ukai, Saori; Ooaku, Kotomi; Oda, Yusuke; Sugimoto, Katsutoshi; Moriyasu, Fuminori; Takagi, Norio; Suzuki, Ryo; Maruyama, Kazuo; Aramaki, Yukihiko

2014-01-01

147

Effects of Verbal and Written Performance Feedback on Treatment Adherence: Practical Application of Two Delivery Formats  

ERIC Educational Resources Information Center

Verbal and written performance feedback for improving preschool and kindergarten teachers' treatment integrity of behavior plans was compared using a combined multiple-baseline and multiple-treatment design across teacher-student dyads with order counterbalanced as within-series conditions. Supplemental generalized least square regression…

Kaufman, Dahlia; Codding, Robin S.; Markus, Keith A.; Tryon, Georgiana Shick; Kyse, Eden Nagler

2013-01-01

148

Case Report: Delivery of Family Therapy in the Treatment of Anorexia Nervosa Using Telehealth  

Microsoft Academic Search

Family therapy plays an important role in the comprehensive treatment of adolescents with anorexia nervosa (AN). However, most comprehensive hospital-based treatment facilities for eating disorders are situated in large urban centers, thus not accessible to individuals living in underserviced rural communities. Telehealth is now being used to provide psychiatric ser- vices to individuals who do not have access to urban-based

Gary S. Goldfield; Ahmed Boachie

2003-01-01

149

Buccal mucosal delivery of a potent peptide leads to therapeutically-relevant plasma concentrations for the treatment of autoimmune diseases.  

PubMed

Stichodactyla helianthus neurotoxin (ShK) is an immunomodulatory peptide currently under development for the treatment of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis by parenteral administration. To overcome the low patient compliance of conventional self-injections, we have investigated the potential of the buccal mucosa as an alternative delivery route for ShK both in vitro and in vivo. After application of fluorescent 5-Fam-ShK to untreated porcine buccal mucosa, there was no detectable peptide in the receptor chamber using an in vitro Ussing chamber model. However, the addition of the surfactants sodium taurodeoxycholate hydrate or cetrimide, and formulation of ShK in a chitosan mucoadhesive gel, led to 0.05-0.13% and 1.1% of the applied dose, respectively, appearing in the receptor chamber over 5h. Moreover, confocal microscopic studies demonstrated significantly enhanced buccal mucosal retention of the peptide (measured by mucosal fluorescence associated with 5-Fam-ShK) when enhancement strategies were employed. Administration of 5-Fam-ShK to mice (10mg/kg in a mucoadhesive chitosan-based gel (3%, w/v) with or without cetrimide (5%, w/w)) resulted in average plasma concentrations of 2.6-16.2nM between 2 and 6h, which were substantially higher than the pM concentrations required for therapeutic activity. This study demonstrated that the buccal mucosa is a promising administration route for the systemic delivery of ShK for the treatment of autoimmune diseases. PMID:25482338

Jin, Liang; Boyd, Ben J; White, Paul J; Pennington, Michael W; Norton, Raymond S; Nicolazzo, Joseph A

2015-02-10

150

Apamin-mediated actively targeted drug delivery for treatment of spinal cord injury: more than just a concept.  

PubMed

Faced with the complex medical challenge presented by spinal cord injuries (SCI) and considering the lack of any available curative therapy, the development of a novel method of delivering existing drugs or candidate agents can be perceived to be as important as the development of new therapeutic molecules. By combining three ingredients currently in clinical use or undergoing testing, we have designed a central nervous system targeted delivery system based on apamin-modified polymeric micelles (APM). Apamin, one of the major components of honey bee venom, serves as the targeting moiety, poly(ethylene glycol) (PEG) distearoylphosphatidylethanolamine (DSPE) serves as the drug-loaded material, and curcumin is used as the therapeutic agent. Apamin was conjugated with NHS (N-hydroxysuccinimide)-PEG-DSPE in a site-specific manner, and APM were prepared by a thin-film hydration method. A formulation comprising 0.5 mol % targeting ligand with 50 nm particle size showed strong targeting efficiency in vivo and was evaluated in pharmacodynamic assays. A 7-day treatment by daily intravenous administration of low doses of APM (corresponding to 5 mg/kg of curcumin) was performed. Significantly enhanced recovery and prolonged survival was found in the SCI mouse model, as compared to sham-treated groups, with no apparent toxicity. A single dose of apamin-conjugated polymers was about 700-fold lower than the LD50 amount, suggesting that APM and apamin have potential for clinical applications as spinal cord targeting ligand for delivery of agents in treatment of diseases of the central nervous system. PMID:25098949

Wu, Jin; Jiang, Hong; Bi, Qiuyan; Luo, Qingsong; Li, Jianjun; Zhang, Yan; Chen, Zhangbao; Li, Chong

2014-09-01

151

Microemulsion-based antifungal gel delivery to nail for the treatment of onychomycosis: formulation, optimization, and efficacy studies.  

PubMed

Onychomycosis is the most common nail disease affecting nail plate and nail bed. Onychomycosis causes onycholysis which creates cavity between the nail plate and nail bed, where drug formulations could be applied, providing a direct contact of drug with the nail bed facilitating drug delivery on the infected area. The purpose of the present study was to design and evaluate the potential of microemulsion-based gel as colloidal carrier for itraconazole for delivery into onycholytic nails for effective treatment of onychomycosis. Itraconazole-loaded microemulsions were prepared and optimized using D-optimal design. The microemulsion containing 6.24 % oil, 36 % Smix, and 57.76 % water was selected as the optimized batch (MEI). The globule size and drug loading of the optimized batch were 48.2 nm and 12.13 mg/ml, respectively. Diffused reflectance FTIR studies were performed to study drug-excipient incompatibility. Ex vivo permeation studies were carried out using bovine hoof and human cadaver skin as models for nail plate and nail bed, respectively. Microemulsion-based itraconazole gel (MBGI) showed better penetration and retention in human skin as well as bovine hoof as compared to commercial preparation (market formulation, MFI). The cumulative amount of itraconazole permeated from the MBGI after 12 h was 73.39?±?3.55 ?g?cm(-2) which was 1.8 times more than MF. MBGI showed significantly higher ex vivo antifungal activity (P?treatment of onychomycosis. PMID:25787325

Barot, Bhavesh S; Parejiya, Punit B; Patel, Hetal K; Mehta, Dharmik M; Shelat, Pragna K

2012-12-01

152

Erythrocyte-mediated delivery of phenylalanine ammonia lyase for the treatment of phenylketonuria in BTBR-Pah(enu2) mice.  

PubMed

Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by defects in the phenylalanine hydroxylase gene. Preclinical and clinical investigations suggest that phenylalanine ammonia lyase (PAL) could be an effective alternative for the treatment of PKU. The aim of this study is to investigate if erythrocytes loaded with PAL may act as a safe delivery system able to overcome bioavailability issues and to provide, in vivo, a therapeutically relevant concentration of enzyme. Murine erythrocytes were loaded with recombinant PAL from Anabaena variabilis (rAvPAL) and their ability to perform as bioreactors was assessed in vivo in adult BTBR-Pah(enu2) mice, the genetic murine model of PKU. Three groups of mice were treated with a single i.v. injection of rAvPAL-RBCs at three different doses to select the most appropriate one for assessment of efficacy. Repeated administrations at 9-10 day-intervals of the selected dose for 10 weeks showed that the therapeutic effect was persistent and not affected by the generation of antibodies induced by the recombinant enzyme. This therapeutic approach deserves further in vivo evaluation either as a potential option for the treatment of PKU patients or as a possible model for the substitutive enzymatic treatment of other inherited metabolic disorders. PMID:25151978

Rossi, Luigia; Pierigè, Francesca; Carducci, Claudia; Gabucci, Claudia; Pascucci, Tiziana; Canonico, Barbara; Bell, Sean M; Fitzpatrick, Paul A; Leuzzi, Vincenzo; Magnani, Mauro

2014-11-28

153

An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease.  

PubMed

Tumor necrosis factor-alpha (TNF-?) plays a central role in the pathogenesis of inflammatory bowel disease (IBD). Anti-TNF-? therapies have shown protective effects against colitis, but an efficient tool for target suppression of its secretion - ideally via oral administration - remains in urgent demand. In the colon tissue, TNF-? is mainly secreted by the colonic macrophages. Here, we report an orally-administrated microspheric vehicle that can target the colonic macrophages and suppress the local expression of TNF-? for IBD treatment. This vehicle is formed by cationic konjac glucomannan (cKGM), phytagel and an antisense oligonucleotide against TNF-?. It was given to dextran sodium sulfate (DSS) colitic mice via gastric perfusion. The unique swelling properties of cKGM enabled the spontaneous release of cKGM& antisense nucleotide (ASO) nano-complex from the phytagel scaffold into the colon lumen, where the ASO was transferred into colonic macrophages via receptor-mediated phagocytosis. The treatment significantly decreased the local level of TNF-? and alleviated the symptoms of colitis in the mice. In summary, our study demonstrates a convenient, orally-administrated drug delivery system that effectively targets colonic macrophages for suppression of TNF-? expression. It may represent a promising therapeutic approach in the treatment of IBD. PMID:25701029

Huang, Zhen; Gan, Jingjing; Jia, Lixin; Guo, Guangxing; Wang, Chunming; Zang, Yuhui; Ding, Zhi; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

2015-04-01

154

Optimal in vitro fertilization in 2020 should reduce treatment burden and enhance care delivery for patients and staff.  

PubMed

This review argues that optimal in vitro fertilization in 2020 should include a way of enhancing the delivery of treatment for patients and staff by the minimization of patient, treatment, and clinic sources of burden. Two specific sources of burden are addressed. First, patient vulnerability can be tackled by implementation of pretreatment evidence-based screening for psychological distress, appropriate referral for support, elimination of barriers to acceptance of psychosocial support, and implementation of a routine care flowchart that identifies the specific stages of treatment when psychosocial support should be provided. Second, negative patient-staff interactions can be avoided by training staff in communication/interaction skills, promoting shared decision making, prioritizing psychological interventions that address aspects of care equally problematic for patients and staff, and monitoring the impact of change on patient, staff, and clinic outcomes. In addition, optimal in vitro fertilization should ensure now that the future generations of young adults know what "achieving parenthood" actually entails in the context of the many desired goals of adulthood, greater variety of reproductive techniques available, later age of first births, and, consequently, longer exposure to risk factors (e.g., smoking) that affect fertility. PMID:23830151

Gameiro, Sofia; Boivin, Jacky; Domar, Alice

2013-08-01

155

An intraperitoneal implantable drug delivery device for the treatment of ovarian cancer  

E-print Network

Ovarian cancer is the fifth leading cause of cancer-related deaths in women and the deadliest gynecologic cancer. The current standard treatment for advanced ovarian cancer includes a minimally invasive cytoreduction ...

Ye, Hongye

2014-01-01

156

Delivery of Evidence-Based Treatment for Multiple Anxiety Disorders in Primary Care: A Randomized Controlled Trial  

PubMed Central

Context Improving the quality of mental health care requires moving clinical interventions from controlled research settings into “real world” practice settings. While such advances have been made for depression, little work has been done for anxiety disorders. Objective To determine whether a flexible treatment-delivery model for multiple primary care anxiety disorders (panic, generalized anxiety, social anxiety, and/or posttraumatic stress disorders) would be superior to usual care. Design, Setting, and Participants Randomized controlled effectiveness trial of CALM (“Coordinated Anxiety Learning and Management”) compared to usual care (UC) in 17 primary care clinics in 4 US cities. Between June 2006 and April 2008, 1004 patients with anxiety disorders (with or without major depression), age 18–75, English- or Spanish-speaking, enrolled and subsequently received treatment for 3–12 months. Blinded follow-up assessments at 6, 12, and 18 months after baseline were completed in October 2009. Intervention(s) CALM allowed choice of cognitive behavioral therapy (CBT), medication, or both; included real-time web-based outcomes monitoring to optimize treatment decisions and a computer-assisted program to optimize delivery of CBT by non-expert care managers who also assisted primary care providers in promoting adherence and optimizing medications. Main Outcome Measure(s) 12-item Brief Symptom Inventory (anxiety and somatic symptoms) score. Secondary outcomes: Proportion of responders (? 50% reduction from pre-treatment BSI-12 score) and remitters (total BSI-12 score < 6). Results Significantly greater improvement for CALM than UC in global anxiety symptoms: BSI-12 group differences of ?2.49 (95% CI, ?3.59 to ?1.40), ?2.63 (95% CI, ?3.73 to ?1.54), and ?1.63 (95% CI, ?2.73 to ?0.53) at 6, 12, and 18 months, respectively. At 12 months, response and remission rates (CALM vs. UC) were 63.66% (58.95–68.37) vs. 44.68% (39.76–49.59), and 51.49% (46.60–56.38) vs. 33.28% (28.62–37.93), with a number needed to treat (NNT) of 5.27 (4.18–7.13) for response and 5.5 (4.32–7.55) for remission. Conclusions For patients with anxiety disorders treated in primary care clinics, a collaborative care intervention, compared to usual care, resulted in greater improvement in anxiety symptoms, functional disability, and quality of care over 18 months. PMID:20483968

Roy-Byrne, Peter; Craske, Michelle G.; Sullivan, Greer; Rose, Raphael D.; Edlund, Mark J.; Lang, Ariel J.; Bystritsky, Alexander; Welch, Stacy Shaw; Chavira, Denise A.; Golinelli, Daniela; Campbell-Sills, Laura; Sherbourne, Cathy D.; Stein, Murray B.

2010-01-01

157

Selective delivery of IFN-? to renal interstitial myofibroblasts: a novel strategy for the treatment of renal fibrosis.  

PubMed

Renal fibrosis leads to end-stage renal disease demanding renal replacement therapy because no adequate treatment exists. IFN-? is an antifibrotic cytokine that may attenuate renal fibrosis. Systemically administered IFN-? causes side effects that may be prevented by specific drug targeting. Interstitial myofibroblasts are the effector cells in renal fibrogenesis. Here, we tested the hypothesis that cell-specific delivery of IFN-? to platelet-derived growth factor receptor ? (PDGFR?)-expressing myofibroblasts attenuates fibrosis in an obstructive nephropathy [unilateral ureteral obstruction (UUO)] mouse model. PEGylated IFN-? conjugated to PDGFR?-recognizing peptide [(PPB)-polyethylene glycol (PEG)-IFN-?] was tested in vitro and in vivo for antifibrotic properties and compared with free IFN-?. PDGFR? expression was >3-fold increased (P < 0.05) in mouse fibrotic UUO kidneys and colocalized with ?-smooth muscle actin-positive (SMA(+)) myofibroblasts. In vitro, PPB-PEG-IFN-? significantly inhibited col1a1, col1a2, and ?-SMA mRNA expression in TGF-?-activated NIH3T3 fibroblasts (P < 0.05). In vivo, PPB-PEG-IFN-? specifically accumulated in PDGFR?-positive myofibroblasts. PPB-PEG-IFN-? treatment significantly reduced renal collagen I, fibronectin, and ?-SMA mRNA and protein expression. Compared with vehicle treatment, PPB-PEG-IFN-? preserved tubular morphology, reduced interstitial T-cell infiltration, and attenuated lymphangiogenesis (all P < 0.05) without affecting peritubular capillary density. PPB-PEG-IFN-? reduced IFN-?-related side effects as manifested by reduced major histocompatibility complex class II expression in brain tissue (P < 0.05 vs. free IFN-?). Our findings demonstrate that specific targeting of IFN-? to PDGFR?-expressing myofibroblasts attenuates renal fibrosis and reduces systemic adverse effects.-Poosti, F., Bansal, R., Yazdani, S., Prakash, J., Post, E., Klok, P., van den Born, J., de Borst, M. H., van Goor, H., Poelstra, K., Hillebrands, J.-L. Selective delivery of IFN-? to renal interstitial myofibroblasts: a novel strategy for the treatment of renal fibrosis. PMID:25466892

Poosti, Fariba; Bansal, Ruchi; Yazdani, Saleh; Prakash, Jai; Post, Eduard; Klok, Pieter; van den Born, Jacob; de Borst, Martin H; van Goor, Harry; Poelstra, Klaas; Hillebrands, Jan-Luuk

2015-03-01

158

Macrophage mediated biomimetic delivery system for the treatment of lung metastasis of breast cancer.  

PubMed

The biomimetic delivery system (BDS) based on special types of endogenous cells like macrophages and T cells, has been emerging as a novel strategy for cancer therapy, due to its tumor homing property and biocompatibility. However, its development is impeded by complicated construction, low drug loading or negative effect on the cell bioactivity. The present report constructed a BDS by loading doxorubicin (DOX) into a mouse macrophage-like cell line (RAW264.7). It was found that therapeutically meaningful amount of DOX could be loaded into the RAW264.7 cells by simply incubation, without significantly affecting the viability of the cells. Drug could release from the BDS and maintain its activity. RAW264.7 cells exhibited obvious tumor-tropic capacity towards 4T1 mouse breast cancer cells both in vitro and in vivo, and drug loading did not alter this tendency. Importantly, the DOX loaded macrophage system showed promising anti-cancer efficacy in terms of tumor suppression, life span prolongation and metastasis inhibition, with reduced toxicity. In conclusion, it is demonstrated that the BDS developed here seems to overcome some of the main issues related to a BDS. The DOX loaded macrophages might be a potential BDS for targeted cancer therapy. PMID:25646783

Fu, Jijun; Wang, Dan; Mei, Dong; Zhang, Haoran; Wang, Zhaoyang; He, Bing; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Zhang, Qiang

2015-04-28

159

Subcutaneous delivery of sumatriptan in the treatment of migraine and primary headache.  

PubMed

Subcutaneous sumatriptan is an effective treatment for pain from acute migraine headache, and can be used in patients with known migraine syndrome and in patients with primary headaches when secondary causes have been excluded. In limited comparative trials, subcutaneous sumatriptan performed in a manner comparable with oral eletriptan and intravenous metoclopramide, was superior to intravenous aspirin and intramuscular trimethobenzamide-diphenhydramine, and was inferior to intravenous prochlorperazine for pain relief. The most common side effects seen with subcutaneous sumatriptan are injection site reactions and triptan sensations. As with all triptans, there is a risk of rare cardiovascular events with subcutaneous sumatriptan and its use should be limited to those without known cerebrovascular disease and limited in those with known cardiovascular risk factors and unknown disease status. In studies of patient preference and tolerability, the subcutaneous formulation has a faster time of onset and high rate of efficacy when compared with the oral formulation, but the oral formulation appears to be better tolerated. It is important to consider the needs of the patient, their past medical history, and what aspects of migraine treatment are most important to the patient when considering treatment of acute migraine or primary headache. Subcutaneous sumatriptan is a good first-line agent for the treatment of pain from acute migraine headaches and primary headaches. PMID:22272067

Moore, Johanna C; Miner, James R

2012-01-01

160

Long-Term Effects of Methylphenidate Transdermal Delivery System Treatment of ADHD on Growth  

ERIC Educational Resources Information Center

Objective: To examine the long-term effects of the methylphenidate transdermal system (MTS) on the growth of children being treated for attention-deficit/hyperactivity disorder. Method: Height, weight, and body mass index (BMI) were measured in 127 children ages 6 to 12 at longitudinal assessments for up to 36 months of treatment with MTS. These…

Faraone, Stephen V.; Giefer, Eldred E.

2007-01-01

161

Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation  

Microsoft Academic Search

Over the last decade a new cancer treatment modality, electrochemotherapy, has emerged. By using short, intense electric pulses that surpass the capacitance of the cell membrane, permeabilization can occur (electroporation). Thus, molecules that are otherwise non-permeant can gain direct access to the cytosol of cells in the treated area.A highly toxic molecule that does not usually pass the membrane barrier

Anita Gothelf; Lluis M Mir; Julie Gehl

2003-01-01

162

Subcutaneous delivery of sumatriptan in the treatment of migraine and primary headache  

PubMed Central

Subcutaneous sumatriptan is an effective treatment for pain from acute migraine headache, and can be used in patients with known migraine syndrome and in patients with primary headaches when secondary causes have been excluded. In limited comparative trials, subcutaneous sumatriptan performed in a manner comparable with oral eletriptan and intravenous metoclopramide, was superior to intravenous aspirin and intramuscular trimethobenzamide-diphenhydramine, and was inferior to intravenous prochlorperazine for pain relief. The most common side effects seen with subcutaneous sumatriptan are injection site reactions and triptan sensations. As with all triptans, there is a risk of rare cardiovascular events with subcutaneous sumatriptan and its use should be limited to those without known cerebrovascular disease and limited in those with known cardiovascular risk factors and unknown disease status. In studies of patient preference and tolerability, the subcutaneous formulation has a faster time of onset and high rate of efficacy when compared with the oral formulation, but the oral formulation appears to be better tolerated. It is important to consider the needs of the patient, their past medical history, and what aspects of migraine treatment are most important to the patient when considering treatment of acute migraine or primary headache. Subcutaneous sumatriptan is a good first-line agent for the treatment of pain from acute migraine headaches and primary headaches. PMID:22272067

Moore, Johanna C; Miner, James R

2012-01-01

163

Cognitive Behavior Therapy for Anxious Adolescents: Developmental Influences on Treatment Design and Delivery  

ERIC Educational Resources Information Center

Anxiety disorders in adolescence are common and disruptive, pointing to a need for effective treatments for this age group. Cognitive behavior therapy (CBT) is one of the most popular interventions for adolescent anxiety, and there is empirical support for its application. However, a significant proportion of adolescent clients continue to report…

Sauter, Floor M.; Heyne, David; Westenberg, P. Michiel

2009-01-01

164

Tea nanoparticles for immunostimulation and chemo-drug delivery in cancer treatment.  

PubMed

Many health benefits have been associated with tea consumption. In an effort to elucidate the source of these health benefits, numerous phytochemicals have been extracted from tea infusions, some of which have demonstrated promise as clinical therapeutics for cancer therapy. Considering the advantageous properties of organic nanoparticles, the purpose of this study is to develop a method for isolating nanoparticles from tea leaves, and explore potential biomedical applications for these nanoparticles. First, an infusion-dialysis procedure for isolating tea nanoparticles (TNPs) from green tea infusions is developed. Second, atomic force microscopy and scanning electron microscopy reveal that the TNPs are spherical with diameters of 100-300 nm. Third, electrophoretic light scattering is used to determine that the TNPs have a zeta potential of -26.52 mV at pH 7.0. Finally, chemical analysis demonstrates that (-) Epigallocatechin gallate, caffeine, and theobromine are not found in the TNPs. Interestingly, the TNPs do enhance the in vitro secretion of cytokines IL-6, TNF-alpha, and G-CSF, as well as the chemokines RANTES, IP-10, MDC from mouse macrophages RAW264.7, indicating an immunostimulatory effect. As a nanocarrier, the TNPs are able to form complexes with doxorubicin (DOX) and have the potential for applications in drug delivery. Further the DOX-loaded TNPs increase the cellular DOX uptake, compared to free DOX, leading to higher cytotoxicity in the A549 human lung cancer and MCF-7 breast cancer cells. More importantly, the DOX-loaded TNPs significantly increase the DOX uptake and cytotoxicity in MCF-7/ADR multidrug resistant breast cancer cells. In this work, an infusion-dialysis procedure is developed for isolation of the TNPs from green tea, and the potential of these nanoparticles as a multifunctional nanocarrier for cancer therapy in vitro is explored. PMID:24749396

Yi, Sijia; Wang, Yongzhong; Huang, Yujian; Xia, Lijin; Sun, Leming; Lenaghan, Scott C; Zhang, Mingjun

2014-06-01

165

Bovine serum albumin-meloxicam nanoaggregates laden contact lenses for ophthalmic drug delivery in treatment of postcataract endophthalmitis.  

PubMed

Postcataract endophthalmitis treatment through eye drops is of low corneal bioavailability and short residence time. The dominant NSAIDs therapy also suffers from severe ocular irritancy and low patients compliance. This study dispersed bovine serum albumin (BSA) coated meloxicam (MX) nanocrystals encapsulating nanoaggregates (BSA-MX-NA) in contact lenses to reduce drug ocular irritancy and increased drug release duration. The BSA-MX-NA (?100 nm) were prepared using acid-base neutralization in aqueous solutions and were dispersed in poly(hydroxylethyl methacrylate) gels, which are common contact lens materials. Drug release studies showed that the gels released the drug for about 5 days. The proposed drug transport mechanism is a diffusion process which can be described by the Ritger-Peppas model with the diffusional exponent n of 0.4768. The drug release can be affected by the gel thickness and the cross-linking degree. A 400 micro thick gels with 100 ?L cross-linker TEGDMA leads to an adequate meloxicam release for therapeutic application. The ocular irritation studies showed that BSA-MX-NA loaded p-HEMA gels are significantly less irritating to the ocular tissues as compared to marketed MX solutions. The developed contact lenses loaded with BSA-MX-NA could be very useful for extended delivery in postcataract endophthalmitis treatment. PMID:25158220

Zhang, Wenji; Zu, Dongni; Chen, Jianting; Peng, Junjie; Liu, Yun; Zhang, Hefeng; Li, Sanming; Pan, Weisan

2014-11-20

166

Colon Delivery of Budesonide Using Solid Dispersion in Dextran for the Treatment and Secondary Prevention of Ulcerative Colitis in Rat  

PubMed Central

Objectives: Ulcerative colitis is characterized by local inflammation. Targeting drugs directly to the site of injury has the benefit of lower adverse effects and more effective therapy. The aim of this study was colon targeted delivery of budesonide to deliver the major part of the drug to the colon. Methods: Matrix tablets of budesonide from solid dispersion of drug with dextran were prepared using different drug to polymer ratios and three molecular weights of dextran. The physical evaluation and drug release behavior were studied. In vivo efficacy of the selected formulation against acetic acid induced colitis in rats was evaluated and compared to the control (untreated) and references (mesalazine and budesonide suspensions) groups. Results: The results showed that solid dispersion of budesonide with dextran in the ratio of 1:7 using molecular weight (MW) of 10,000 dextran (SDT710) released 25% of the drug in the first 6 hours and 100% in caecal and colonic contents. It could target the drug to colon with improvement in some of the inflammatory signs of induced ulcerative colitis in rat. Treatment with SDT710 could improve not only the percent of involvement also macroscopic damage parameters. The macroscopic parameters included weight/length ratio of the colon, ulcer area, damage score, and ulcer index reduced in comparison to the control group and conventional suspension of budesonide; however, only weight/length ratio was significant. Conclusions: In the experimental model studied, the new colonic delivery system significantly improved the efficacy of budesonide in the weight/length ratio of the colon in induced colitis in rats. PMID:21566772

Varshosaz, Jaleh; Ahmadi, Fatemeh; Emami, Jaber; Tavakoli, Naser; Minaiyan, Mohsen; Mahzouni, Parvin; Dorkoosh, Farid

2010-01-01

167

An adaptive drug delivery design using neural networks for effective treatment of infectious diseases: a simulation study.  

PubMed

An adaptive drug delivery design is presented in this paper using neural networks for effective treatment of infectious diseases. The generic mathematical model used describes the coupled evolution of concentration of pathogens, plasma cells, antibodies and a numerical value that indicates the relative characteristic of a damaged organ due to the disease under the influence of external drugs. From a system theoretic point of view, the external drugs can be interpreted as control inputs, which can be designed based on control theoretic concepts. In this study, assuming a set of nominal parameters in the mathematical model, first a nonlinear controller (drug administration) is designed based on the principle of dynamic inversion. This nominal drug administration plan was found to be effective in curing "nominal model patients" (patients whose immunological dynamics conform to the mathematical model used for the control design exactly. However, it was found to be ineffective in curing "realistic model patients" (patients whose immunological dynamics may have off-nominal parameter values and possibly unwanted inputs) in general. Hence, to make the drug delivery dosage design more effective for realistic model patients, a model-following adaptive control design is carried out next by taking the help of neural networks, that are trained online. Simulation studies indicate that the adaptive controller proposed in this paper holds promise in killing the invading pathogens and healing the damaged organ even in the presence of parameter uncertainties and continued pathogen attack. Note that the computational requirements for computing the control are very minimal and all associated computations (including the training of neural networks) can be carried out online. However it assumes that the required diagnosis process can be carried out at a sufficient faster rate so that all the states are available for control computation. PMID:19215995

Padhi, Radhakant; Bhardhwaj, Jayender R

2009-06-01

168

Intracochlear Drug Delivery Systems  

PubMed Central

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

Borenstein, Jeffrey T.

2011-01-01

169

Synergistic co-delivery of doxorubicin and paclitaxel by porous PLGA microspheres for pulmonary inhalation treatment.  

PubMed

PLGA porous microspheres loaded with doxorubicin (DOX) and paclitaxel (PTX) were developed for in situ treatment of metastatic lung cancer. The synergistic effect of the combined drugs was investigated against B16F10 cells to obtain the optimal prescription for in vivo studies. The combination therapy showed great synergism when DOX was the majority in the combination therapy, while they showed moderate antagonism when PTX is in major. The combination of DOX and PTX at a molar ratio of 5/1 showed the best synergistic therapeutic effect in the free form. However, the drugs exhibited more synergism in the PLGA microspheres at a molar ratio of 2/1, due to the difference in drug release rate. The in vivo study verified the synergism of DOX and PTX at the optimal molar ratio. These results suggested that dual encapsulation of DOX and PTX in porous PLGA microspheres would be a promising technology for long effective lung cancer treatment. PMID:25305583

Feng, Tianshi; Tian, Huayu; Xu, Caina; Lin, Lin; Xie, Zhigang; Lam, Michael Hon-Wah; Liang, Haojun; Chen, Xuesi

2014-11-01

170

Staff perceptions of organization change of treatment delivery on an addiction unit.  

PubMed

The Work Environment Scale was used to assess staff perceptions of a change in a treatment programme for problem drinkers. A more cost-effective 2-week research-based day-patient programme, which included the concept of matching, replaced a 5-week cognitive behavioural in-patient programme. The maintenance of a positive work environment was attributed to the meeting of staff expectations, a cognitive behavioural ideology, and the establishment of a research culture. The study highlights the importance of the thorough preparation of staff for change, and their active involvement in the process in settings where work satisfaction is already above the average level for mental health facilities. PMID:7797714

Long, C G; Williams, M; Hollin, C R

1995-04-01

171

Intrafraction tumor motion management techniques in imaging, treatment planning, and IMRT delivery  

NASA Astrophysics Data System (ADS)

Anatomic motion can affect the radiation treatment of disease sites in the thorax and abdomen. With four dimensional (4D) imaging modalities, respiratory motion can be defined on a patient specific basis. From 4D data sets, radiotherapy techniques can be devised to account for tissue motion. Systematic and random uncertainties must be characterized for each 4D imaging modality utilized. Some modalities, such as 4D-CT, require multiple motion trajectories in order to fully define the uncertainties associated with the imaging system. This is investigated in this work for a clinical 4D-CT scanning protocol and the methods used can be applied to any 4D imaging modality. Once all of the relevant tissues and their associated motion have been defined, with corrections to account for any associated uncertainties in the 4D data sets, treatment plans can be generated. For lung cancer, unique challenges arise when inverse planning is used, typically in the case of IMRT, because density differences between lung tissue and other tissues can result in quite different dose distributions. Because inverse planning is an optimization algorithm, the degree of optimization is dependent on the input parameters. One important input factor is the image set that is used for the dose calculation. For three image sets supplied to a commercial inverse planning algorithm (Average Image and an exhale phase image with motion envelope defined from a maximum intensity projection image, both with and without a density override to the motion envelope), dose calculated on the Average Image was found to be in best agreement with the dose calculated on the 4D-CT. Finally, when IMRT is delivered to mobile tumors, it is possible for the dose to the tumor to vary from treatment to treatment. Therefore, numerous methods have been investigated in order to reduce this variation. A computer simulation algorithm has been developed to predict the variation on a two spatial dimension plane and comparisons are made with measured data in a similar configuration. Variable tumor motion has also been considered in this respect.

Ehler, Eric Drew

172

New scanner fiber optic delivery system for laser phototherapy in the treatment of neonatal jaundice  

NASA Astrophysics Data System (ADS)

The authors have introduced laser phototherapy for the treatment of neonatal jaundice. Clinical trials have demonstrated its high efficacy compared to the conventionally used fluorescent phototherapy. In this paper a new modification to laser irradiation in phototherapy can be achieved by scanning the laser output beam in the selected wavelength of irradiation (488 nm) through a fiberoptic bundle which irradiate the skin of the baby. Scanning of the laser beam provides intermittent irradiation at high frequency, which can provide the same therapeutic efficacy with almost half the power of laser irradiation.

Hamza, Mostafa; Hamza, Mohammad S. E.

1995-05-01

173

Lemongrass essential oil gel as a local drug delivery agent for the treatment of periodontitis  

PubMed Central

Background: It has been long recognized that periodontal diseases are infections of the periodontium, comprising the bacterial etiology, an immune response, and tissue destruction. Treatment strategies aiming primarily at suppressing or eliminating specific periodontal pathogens include adjunct use of local and systemic antibiotics as part of nonsurgical periodontal therapy. Unwanted side effects and resistance of microorganisms toward antibiotics due to their widespread use have modified the general perception about their efficacy. Research in phytosciences has revealed various medicinal plants offering a new choice of optional antimicrobial therapy. Cymbopogon citratus, Stapf. (lemongrass) is a popular medicinal plant. At a concentration ?2%, lemongrass essential oil inhibits the growth of several kinds of microorganisms including periodontal pathogens, especially the reference strains Actinomyces naeslundii and Porphyromonas gingivalis, which were resistant to tetracycline hydrochloride. Aims: To evaluate the efficacy of locally delivered 2% lemongrass essential oil in gel form as an adjunct to scaling and root planing, as compared to scaling and root planing alone for the treatment of chronic periodontitis. Materials and Methods: 2% Lemongrass essential oil gel was prepared and placed in moderate to deep periodontal pockets after scaling and root planing. Results: Statistically significant reduction in probing depth and gingival index and gain in relative attachment level were noted in the experimental group as compared to the control group at 1 and 3 months. Conclusion: Locally delivered 2% lemongrass essential oil gel offers a new choice of safe and effective adjunct to scaling and root planing in periodontal therapy. PMID:24991068

Warad, Shivaraj B.; Kolar, Sahana S.; Kalburgi, Veena; Kalburgi, Nagaraj B.

2013-01-01

174

Double layer adhesive silicone dressing as a potential dermal drug delivery film in scar treatment.  

PubMed

The present studies focused on the evaluation of design of an adhesive silicone film intended for scar treatment. Developed silicone double layer film was examined in terms of its future relevance to therapy and applicability on the human skin considering properties which included in vitro permeability of water vapor and oxygen. In order to adapt the patches for medical use in the future there were tested such properties as in vitro adhesion and occlusion related to in vivo hydration. From the silicone rubbers double layer silicone film was prepared: a non-adhesive elastomer as a drug carrier (the matrix for active substances - enoxaparin sodium - low molecular weight heparin) and an adhesive elastomer, applied on the surface of the matrix. The novel adhesive silicone film was found to possess optimal properties in comparison to commercially available silicone dressing: adhesion in vivo, adhesion in vitro - 11.79N, occlusion F=85% and water vapor permeability in vitro - WVP=105g/m(2)/24h, hydration of stratum corneum in vivoH=61-89 (RSD=1.6-0.9%), oxygen permeation in vitro - 119-391cm(3)/m(2)/24 (RSD=0.17%). In vitro release studies indicated sufficient LMWH release rate from silicone matrix. Developed novel adhesive silicone films were considered an effective treatment of scars and keloids and a potential drug carrier able to improve the effectiveness of therapy. PMID:25639195

Mojsiewicz-Pie?kowska, Krystyna; Jamrógiewicz, Marzena; ?ebrowska, Maria; Mikolaszek, Barbara; Sznitowska, Ma?gorzata

2015-03-15

175

The impacts of dental filling materials on RapidArc treatment planning and dose delivery: Challenges and solution  

SciTech Connect

Purpose: The presence of high-density material in the oral cavity creates dose perturbation in both downstream and upstream directions at the surfaces of dental filling materials (DFM). In this study, the authors have investigated the effect of DFM on head and neck RapidArc treatment plans and delivery. Solutions are proposed to address (1) the issue of downstream dose perturbation, which might cause target under dosage, and (2) to reduce the upstream dose from DFM which may be the primary source of mucositis. In addition, an investigation of the clinical role of a custom-made plastic dental mold/gutter (PDM) in sparing the oral mucosa and tongue reaction is outlined.Methods: The influence of the dental filling artifacts on dose distribution was investigated using a geometrically well-defined head and neck intensity modulated radiation therapy (IMRT) verification phantom (PTW, Freiberg, Germany) with DFM inserts called amalgam, which contained 50% mercury, 25% silver, 14% tin, 8% copper, and 3% other trace metals. Three RapidArc plans were generated in the Varian Eclipse System to treat the oral cavity using the same computer tomography (CT) dataset, including (1) a raw CT image, (2) a streaking artifacts region, which was replaced with a mask of 10 HU, and (3) a 2 cm-thick 6000 HU virtual filter [a volume created in treatment planning system to compensate for beam attenuation, where the thickness of this virtual filter is based on the measured percent depth dose (PDD) data and Eclipse calculation]. The dose delivery for the three plans was verified using Gafchromic-EBT2 film measurements. The custom-made PDM technique to reduce backscatter dose was clinically tested on four head and neck cancer patients (T3, N1, M0) with DFM, two patients with PDM and the other two patients without PDM. The thickness calculation of the PDM toward the mucosa and tongue was purely based on the measured upstream dose. Patients’ with oral mucosal reaction was clinically examined initially and weekly during the course of radiotherapy.Results: For a RapidArc treatment technique, the backscatter dose from the DFM insert was measured to be 9.25 ± 2.17 in the IMRT-verification-phantom. The measured backscatter upstream dose from DFM for a single-field was 22% higher than without the DFM, whereas the downstream dose was lower by 14%. The values of homogeneity index for the plans with and without the application of mask were 0.09 and 0.14, respectively. The calculated mean treatment planning volume (PTV) dose differed from the delivered dose by 13% and was reduced to 2% when using the mask and virtual filter together. A grade 3 mucosa reaction was observed in the control group after 22–24 fractions (44–48 Gy). In contrast, no grade 3 mucositis was observed in the patients wearing the PDM after 25–26 fractions (50–52 Gy).Conclusions: The backscatter from the DFM for a single, parallel-opposed fields, and RapidArc treatment technique was found significant. The application of mask in replacing streaking artifacts can be useful in improving dose homogeneity in the PTV. The use of a virtual filter around the teeth during the planning phase reduces the target underdosage issue in the phantom. Furthermore, a reduction in mucositis is observed in the head and neck patients with the use of PDM.

Mail, Noor; Al-Ghamdi, S.; Saoudi, A. [Princess Norah Oncology Center, National Guard Health Affairs, Jeddah 21423, Saudi Arabia and King Abdullah International Medical Research Center, Jeddah 21423 (Saudi Arabia)] [Princess Norah Oncology Center, National Guard Health Affairs, Jeddah 21423, Saudi Arabia and King Abdullah International Medical Research Center, Jeddah 21423 (Saudi Arabia); Albarakati, Y.; Ahmad Khan, M.; Saeedi, F.; Safadi, N. [Princess Norah Oncology Center, National Guard Health Affairs, Jeddah 21423 (Saudi Arabia)] [Princess Norah Oncology Center, National Guard Health Affairs, Jeddah 21423 (Saudi Arabia)

2013-08-15

176

One System Integrated Project Team: Retrieval And Delivery Of The Hanford Tank Wastes For Vitrification In The Waste Treatment Plant  

SciTech Connect

The One System Integrated Project Team (IPT) was formed in late 2011 as a way for improving the efficiency of delivery and treatment of highly radioactive waste stored in underground tanks at the U.S. Department of Energy's (DOE's) 586-square-mile Hanford Site in southeastern Washington State. The purpose of the One System IPT is to improve coordination and integration between the Hanford's Waste Treatment Plant (WTP) contractor and the Tank Operations Contractor (TOC). The vision statement is: One System is a WTP and TOC safety conscious team that, through integrated management and implementation of risk-informed decision and mission-based solutions, will enable the earliest start of safe and efficient treatment of Hanford's tank waste, to protect the Columbia River, environment and public. The IPT is a formal collaboration between Bechtel National, Inc. (BNI), which manages design and construction of the WTP for the U.S. Department of Energy's Office of River Protection (DOEORP), and Washington River Protection Solutions (WRPS), which manages the TOC for ORP. More than fifty-six (56) million gallons of highly radioactive liquid waste are stored in one hundred seventy-seven (177) aging, underground tanks. Most of Hanford's waste tanks - one hundred forty-nine (149) of them - are of an old single-shell tank (SST) design built between 1944 and 1964. More than sixty (60) of these tanks have leaked in the past, releasing an estimated one million gallons of waste into the soil and threatening the nearby Columbia River. There are another twenty-eight (28) new double-shelled tanks (DSTs), built from 1968 to 1986, that provide greater protection to the environment. In 1989, DOE, the U.S. Environmental Protection Agency (EPA), and the Washington State Department of Ecology (Ecology) signed a landmark agreement that required Hanford to comply with federal and state environmental standards. It also paved the way for agreements that set deadlines for retrieving the tank wastes and for building and operating the WTP. The tank wastes are the result of Hanford's nearly fifty (50) years of plutonium production. In the intervening years, waste characteristics have been increasingly better understood. However, waste characteristics that are uncertain and will remain as such represent a significant technical challenge in terms of retrieval, transport, and treatment, as well as for design and construction ofWTP. What also is clear is that the longer the waste remains in the tanks, the greater the risk to the environment and the people of the Pacific Northwest. The goal of both projects - tank operations and waste treatment - is to diminish the risks posed by the waste in the tanks at the earliest possible date. About two hundred (200) WTP and TOC employees comprise the IPT. Individual work groups within One System include Technical, Project Integration & Controls, Front-End Design & Project Definition, Commissioning, Nuclear Safety & Engineering Systems Integration, and Environmental Safety and Health and Quality Assurance (ESH&QA). Additional functions and team members will be added as the WTP approaches the operational phase. The team has undertaken several initiatives since its formation to collaborate on issues: (1) alternate scenarios for delivery of wastes from the tank farms to WTP; (2) improvements in managing Interface Control Documents; (3) coordination on various technical issues, including the Defense Nuclear Facilities Nuclear Safety Board's Recommendation 2010-2; (4) deployment of the SmartPlant? Foundation-configuration Management System; and (5) preparation of the joint contract deliverable of the Operational Readiness Support Plan.

Harp, Benton J. [Department of Energy, Office of River Protection, Richland, Washington (United States); Kacich, Richard M. [Bechtel National, Inc., Richland, WA (United States); Skwarek, Raymond J. [Washington River Protection Solutions LLC, Richland, WA (United States)

2012-12-20

177

One System Integrated Project Team: Retrieval and Delivery of Hanford Tank Wastes for Vitrification in the Waste Treatment Plant - 13234  

SciTech Connect

The One System Integrated Project Team (IPT) was formed in late 2011 as a way for improving the efficiency of delivery and treatment of highly radioactive waste stored in underground tanks at the U.S. Department of Energy's (DOE's) 586-square-mile Hanford Site in southeastern Washington State. The purpose of the One System IPT is to improve coordination and integration between the Hanford's Waste Treatment Plant (WTP) contractor and the Tank Operations Contractor (TOC). The vision statement is: One System is a WTP and TOC safety-conscious team that, through integrated management and implementation of risk-informed decision and mission-based solutions, will enable the earliest start of safe and efficient treatment of Hanford's tank waste, to protect the Columbia River, environment and public. The IPT is a formal collaboration between Bechtel National, Inc. (BNI), which manages design and construction of the WTP for the U.S. Department of Energy's Office of River Protection (DOEORP), and Washington River Protection Solutions (WRPS), which manages the TOC for ORP. More than fifty-six (56) million gallons of highly radioactive liquid waste are stored in one hundred seventy-seven (177) aging, underground tanks. Most of Hanford's waste tanks - one hundred forty-nine (149) of them - are of an old single-shell tank (SST) design built between 1944 and 1964. More than sixty (60) of these tanks have leaked in the past, releasing an estimated one million gallons of waste into the soil and threatening the nearby Columbia River. There are another twenty-eight (28) new double-shelled tanks (DSTs), built from 1968 to 1986, that provide greater protection to the environment. In 1989, DOE, the U.S. Environmental Protection Agency (EPA), and the Washington State Department of Ecology (Ecology) signed a landmark agreement that required Hanford to comply with federal and state environmental standards. It also paved the way for agreements that set deadlines for retrieving the tank wastes and for building and operating the WTP. The tank wastes are the result of Hanford's nearly fifty (50) years of plutonium production. In the intervening years, waste characteristics have been increasingly better understood. However, waste characteristics that are uncertain and will remain as such represent a significant technical challenge in terms of retrieval, transport, and treatment, as well as for design and construction of WTP. What also is clear is that the longer the waste remains in the tanks, the greater the risk to the environment and the people of the Pacific Northwest. The goal of both projects - tank operations and waste treatment - is to diminish the risks posed by the waste in the tanks at the earliest possible date. About two hundred (200) WTP and TOC employees comprise the IPT. Individual work groups within One System include Technical, Project Integration and Controls, Front-End Design and Project Definition, Commissioning, Nuclear Safety and Engineering Systems Integration, and Environmental Safety and Health and Quality Assurance (ESH and QA). Additional functions and team members will be added as the WTP approaches the operational phase. The team has undertaken several initiatives since its formation to collaborate on issues: (1) alternate scenarios for delivery of wastes from the tank farms to WTP; (2) improvements in managing Interface Control Documents; (3) coordination on various technical issues, including the Defense Nuclear Facilities Nuclear Safety Board's Recommendation 2010-2; (4) deployment of the SmartPlant{sup R} Foundation-Configuration Management System; and (5) preparation of the joint contract deliverable of the Operational Readiness Support Plan. (authors)

Harp, Benton J. [U.S. Department of Energy, Office of River Protection, Post Office Box 550, Richland, Washington 99352 (United States)] [U.S. Department of Energy, Office of River Protection, Post Office Box 550, Richland, Washington 99352 (United States); Kacich, Richard M. [Bechtel National, Inc., 2435 Stevens Center Place, Richland, Washington 99354 (United States)] [Bechtel National, Inc., 2435 Stevens Center Place, Richland, Washington 99354 (United States); Skwarek, Raymond J. [Washington River Protection Solutions LLC, Post Office Box 850, Richland, Washington 99352 (United States)] [Washington River Protection Solutions LLC, Post Office Box 850, Richland, Washington 99352 (United States)

2013-07-01

178

Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles.  

PubMed

The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood?brain?tumor barrier. In the present study, cyclic Arginine?Glycine?Aspartic acid?D?Tyrosine?Lysine [c(RGDyK)], that has a high binding affinity to integrin ?v?3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid?polyethylene glycol (DTX?PLA?PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine?Glycine?Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX?PLA?PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non?targeted micelles showed limited transport ability. Furthermore, RGD?linked micelles showed marked anti?glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand?mediated drug delivery may improve the efficacy of brain cancer chemotherapy. PMID:25434368

Li, Ai-Jun; Zheng, Yue-Hua; Liu, Guo-Dong; Liu, Wei-Sheng; Cao, Pei-Cheng; Bu, Zhen-Fu

2015-04-01

179

Commercial Environmental Cleanup -- The products and services directory. Treatment, characterization and extraction/delivery/materials handling technologies  

SciTech Connect

This directory is patterned after the telephone Yellow Pages and is designed as a reference tool to those who may seek commercial remedies for their environmental cleanup problems. It offers the user the opportunity to survey 325 environmental cleanup businesses that currently market their products and services through 1,134 applications of commercially available technologies. Like the Yellow Pages, the Directory furnishes the user with points-of-contact to investigate the capabilities of the listed companies to perform within acceptable standards, practices, and costs and to meet a user`s specific needs. The three major sections of the Directory are organized under the broad headings of Treatment, Characterization, and Extraction/Delivery/Materials Handling. Within each section, information is grouped according to the applicable contaminant medium and companies are listed alphabetically under each medium heading. Not all vendors in the environmental cleanup business are included in this first edition of the Directory. Future editions will more completely reflect the status of the industry. The database of the commercial cleanup products and services Directory will be offered on the Internet in the future and will be available on the Homepage www.doe.gjpo.com.

NONE

1995-11-01

180

Co-delivery of antiviral and antifungal therapeutics for the treatment of sexually transmitted infections using a moldable, supramolecular hydrogel.  

PubMed

In this investigation, a therapeutic co-delivery hydrogel system is developed to provide effective HIV prophylaxis, alongside the prevention and/or treatment of candidiasis. Two components-a HIV reverse transcriptase inhibitor, tenofovir, and a cationic macromolecular antifungal agent derived from a vitamin D-functionalized polycarbonate (VD/BnCl (1:30))-are formulated into biodegradable vitamin D-functionalized polycarbonate/PEG-based supramolecular hydrogels. The hydrogels exhibit thixotropic properties and can be easily spread across surfaces for efficient drug absorption. Sustained release of tenofovir from the hydrogel is observed, where approximately 85% tenofovir is released within 3 h. VD/BnCl (1:30) does not impede drug diffusion from the hydrogel as the drug release profiles are similar with and without the polycation. Antimicrobial efficacy studies indicate that the hydrogels kill C. albicans efficiently with a minimum bactericidal concentration (MBC) of 0.25-0.5 g L(-1) . These hydrogels also eradicate C. albicans biofilm effectively at 4× MBC. When human dermal fibroblasts (as model mammalian cells) are treated with these hydrogels, cell viability remains high at above 80%, demonstrating excellent biocompatibility. When applied topically, this dual-functional hydrogel can potentially prevent HIV transmission and eliminate microbes that cause infections in the vulvovagina region. PMID:25234003

Lee, Ashlynn L Z; Ng, Victor W L; Poon, Ghim Lee; Ke, Xiyu; Hedrick, James L; Yang, Yi Yan

2015-02-18

181

Are mobile phones and handheld computers being used to enhance delivery of psychiatric treatment? A systematic review.  

PubMed

The rapid diffusion of communication technology has provided opportunities to enhance the delivery of mental health care. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct a qualitative review of randomized controlled trials that reported on the efficacy of mobile phones or handheld computers used to enhance the treatment of psychiatric disorders. We identified eight randomized controlled trials. Five studies used mobile phones to target smoking cessation. Those receiving the smoking cessation intervention were significantly more likely to achieve abstinence compared with those under the control condition. Three studies used non-personal digital assistant (PDA) handheld computers targeting anxiety. Compared with those in the control condition, those who received the non-PDA handheld computer intervention had significant improvement in anxiety outcomes in only one of the three studies. The limited number of rigorous evaluations of mobile phone, PDA, or smartphone interventions for mental health problems underscores the opportunities to enhance our interventions using the available tools of contemporary technology. PMID:22048142

Ehrenreich, Benjamin; Righter, Bryan; Rocke, Di Andra; Dixon, Lisa; Himelhoch, Seth

2011-11-01

182

Formulation, characterization and evaluation of cyclodextrin-complexed bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer treatment.  

PubMed

Abstract PLGA nanospheres are considered to be promising drug carrier in the treatment of cancer. Inclusion complex of bendamustine (BM) with epichlorohydrin beta cyclodextrin polymer was prepared by freeze-drying method. Phase solubility study revealed formation of AL type complex with stability constant (Ks?=?645?M(-1)). This inclusion complex was encapsulated into PLGA nanospheres using solid-in-oil-in-water (S/O/W) technique. The particle size and zeta potential of PLGA nanospheres loaded with cyclodextrin-complexed BM were about 151.4?±?2.53?nm and?-?31.9?±?(-3.08)?mV. In-vitro release study represented biphasic release pattern with 20% burst effect and sustained slow release. DSC studies indicated that inclusion complex incorporated in PLGA nanospheres was not in a crystalline state but existed in an amorphous or molecular state. The cytotoxicity experiment was studied in Z-138 cells and IC50 value was found to be 4.3?±?0.11?µM. Cell viability studies revealed that the PLGA nanospheres loaded with complex exerts a more pronounced effect on the cancer cells as compared to the free drug. In conclusion, PLGA nanospheres loaded with inclusion complex of BM led to sustained drug delivery. The nanospheres were stable after 3 months of storage conditions with slight change in their particle size, zeta potential and entrapment efficiency. PMID:25391288

Gidwani, Bina; Vyas, Amber

2014-11-13

183

New silica nanostructure for the improved delivery of topical antibiotics used in the treatment of staphylococcal cutaneous infections.  

PubMed

In this paper, we report the synthesis, characterization (FT-IR, XRD, BET, HR-TEM) and bioevaluation of a novel ?-aminobutiric acid/silica (noted GABA-SiO? or ?-SiO?) hybrid nanostructure, for the improved release of topical antibiotics, used in the treatment of Staphylococcus aureus infections. GABA-SiO? showed IR bands which were assigned to Si-O-Si (stretch mode). The XRD pattern showed a broad peak in the range of 18-30° (2?), indicating an amorphous structure. Based on the BET analysis, estimations about surface area (438.14 m²/g) and pore diameters (4.76 nm) were done. TEM observation reveals that the prepared structure presented homogeneity and an average size of particles not exceeding 10nm. The prepared nanostructure has significantly improved the anti-staphylococcal activity of bacitracin and kanamycin sulfate, as demonstrated by the drastic decrease of the minimal inhibitory concentration of the respective antibiotics loaded in the GABA-SiO? nanostructure. These results, correlated with the high biocompatibility of this porous structure, are highlighting the possibility of using this carrier for the local delivery of the antimicrobial substances in lower active doses, thus reducing their cytotoxicity and side-effects. PMID:23871740

Grumezescu, Alexandru Mihai; Ghitulica, Cristina Daniela; Voicu, Georgeta; Huang, Keng-Shiang; Yang, Chih-Hui; Ficai, Anton; Vasile, Bogdan Stefan; Grumezescu, Valentina; Bleotu, Coralia; Chifiriuc, Mariana Carmen

2014-03-25

184

Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment.  

PubMed

In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 ?g 5-FU/g rat colon content vs 4.66 ?g/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach. PMID:24709212

Bose, A; Elyagoby, A; Wong, T W

2014-07-01

185

Intravenous delivery of camptothecin-loaded PLGA nanoparticles for the treatment of intracranial glioma.  

PubMed

Effective treatment of glioblastoma multiforme remains a major clinical challenge, due in part to the difficulty of delivering chemotherapeutics across the blood-brain barrier. Systemically administered drugs are often poorly bioavailable in the brain, and drug efficacy within the central nervous system can be limited by peripheral toxicity. Here, we investigate the ability of systemically administered poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) to deliver hydrophobic payloads to intracranial glioma. Hydrophobic payload encapsulated within PLGA NPs accumulated at ?10× higher levels in tumor compared to healthy brain. Tolerability of the chemotherapeutic camptothecin (CPT) was improved by encapsulation, enabling safe administration of up to 20mg/kg drug when encapsulated within NPs. Immunohistochemistry staining for ?-H2AFX, a marker for double-strand breaks, demonstrated higher levels of drug activity in tumors treated with CPT-loaded NPs compared to free drug. CPT-loaded NPs were effective in slowing the growth of intracranial GL261 tumors in immune competent C57 albino mice, providing a significant survival benefit compared to mice receiving saline, free CPT or low dose CPT NPs (median survival of 36.5 days compared to 28, 32, 33.5 days respectively). In sum, these data demonstrate the feasibility of treating intracranial glioma with systemically administered nanoparticles loaded with the otherwise ineffective chemotherapeutic CPT. PMID:25562639

Householder, Kyle T; DiPerna, Danielle M; Chung, Eugene P; Wohlleb, Gregory M; Dhruv, Harshil D; Berens, Michael E; Sirianni, Rachael W

2015-02-20

186

Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review  

PubMed Central

Homeostasis of metal ions such as Zn2+ is essential for proper brain function. Moreover, the list of psychiatric and neurodegenerative disorders involving a dysregulation of brain Zn2+-levels is long and steadily growing, including Parkinson’s and Alzheimer’s disease as well as schizophrenia, attention deficit and hyperactivity disorder, depression, amyotrophic lateral sclerosis, Down's syndrome, multiple sclerosis, Wilson’s disease and Pick’s disease. Furthermore, alterations in Zn2+-levels are seen in transient forebrain ischemia, seizures, traumatic brain injury and alcoholism. Thus, the possibility of altering Zn2+-levels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. Although the role of Zn2+ in the brain has been extensively studied over the past decades, methods for controlled regulation and manipulation of Zn2+ concentrations within the brain are still in their infancy. Since the use of dietary Zn2+ supplementation and restriction has major limitations, new methods and alternative approaches are currently under investigation, such as the use of intracranial infusion of Zn2+ chelators or nanoparticle technologies to elevate or decrease intracellular Zn2+ levels. Therefore, this review briefly summarizes the role of Zn2+ in psychiatric and neurodegenerative diseases and highlights key findings and impediments of brain Zn2+-level manipulation. Furthermore, some methods and compounds, such as metal ion chelation, redistribution and supplementation that are used to control brain Zn2+-levels in order to treat brain disorders are evaluated. PMID:22102982

Grabrucker, Andreas M.; Rowan, Magali; Garner, Craig C.

2011-01-01

187

Bimatoprost-Loaded Ocular Inserts as Sustained Release Drug Delivery Systems for Glaucoma Treatment: In Vitro and In Vivo Evaluation  

PubMed Central

The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM). Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM) were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP) was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a promising system for glaucoma management. PMID:24788066

Franca, Juçara Ribeiro; Foureaux, Giselle; Fuscaldi, Leonardo Lima; Ribeiro, Tatiana Gomes; Rodrigues, Lívia Bomfim; Bravo, Renata; Castilho, Rachel Oliveira; Yoshida, Maria Irene; Cardoso, Valbert Nascimento; Fernandes, Simone Odília; Cronemberger, Sebastião; Ferreira, Anderson José; Faraco, André Augusto Gomes

2014-01-01

188

Chimeric Human Skin Substitute Tissue: A Novel Treatment Option for the Delivery of Autologous Keratinocytes  

PubMed Central

Background For patients suffering from catastrophic burns, few treatment options are available. Chimeric coculture of patient-derived autologous cells with a “carrier” cell source of allogeneic keratinocytes has been proposed as a means to address the complex clinical problem of severe skin loss. The Problem Currently, autologous keratinocytes are harvested, cultured, and expanded to form graftable epidermal sheets. However, epidermal sheets are thin, are extremely fragile, and do not possess barrier function, which only develops as skin stratifies and matures. Grafting is typically delayed for up to 4 weeks to propagate a sufficient quantity of the patient's cells for application to wound sites. Basic/Clinical Science Advances Fully stratified chimeric bioengineered skin substitutes could not only provide immediate wound coverage and restore barrier function, but would simultaneously deliver autologous keratinocytes to wounds. The ideal allogeneic cell source for this application would be an abundant supply of clinically evaluated, nontumorigenic, pathogen-free, human keratinocytes. To evaluate this potential cell-based therapy, mixed populations of a green fluorescent protein-labeled neonatal human keratinocyte cell line (NIKS) and unlabeled primary keratinocytes were used to model the allogeneic and autologous components of chimeric monolayer and organotypic cultures. Clinical Care Relevance Relatively few autologous keratinocytes may be required to produce fully stratified chimeric skin substitute tissue substantially composed of autologous keratinocyte-derived regions. The need for few autologous cells interspersed within an allogeneic “carrier” cell population may decrease cell expansion time, reducing the time to patient application. Conclusion This study provides proof of concept for utilizing NIKS keratinocytes as the allogeneic carrier for the generation of bioengineered chimeric skin substitute tissues capable of providing immediate wound coverage while simultaneously supplying autologous human cells for tissue regeneration. PMID:24527281

Rasmussen, Cathy A.; Allen-Hoffmann, B. Lynn

2012-01-01

189

Co-delivery of docetaxel and endostatin by a biodegradable nanoparticle for the synergistic treatment of cervical cancer  

NASA Astrophysics Data System (ADS)

Cervical cancer remains a major problem in women's health worldwide. In this research, a novel biodegradable d-?-tocopheryl polyethylene glycol 1000 succinate- b-poly(?-caprolactone- ran-glycolide) (TPGS- b-(PCL- ran-PGA)) nanoparticle (NP) was developed as a co-delivery system of docetaxel and endostatin for the synergistic treatment of cervical cancer. Docetaxel-loaded TPGS- b-(PCL- ran-PGA) NPs were prepared and further modified by polyethyleneimine for coating plasmid pShuttle2-endostatin. All NPs were characterized in size, surface charge, morphology, and in vitro release of docetaxel and pDNA. The uptake of coumarin 6-loaded TPGS- b-(PCL- ran-PGA)/PEI-pDsRED by HeLa cells was observed via fluorescent microscopy and confocal laser scanning microscopy. Endostatin expression in HeLa cells transfected by TPGS- b-(PCL- ran-PGA)/PEI-pShuttle2-endostatin NPs was detected using Western blot analysis, and the cell viability of different NP-treated HeLa cells was determined by MTT assay. The HeLa cells from the tumor model, nude mice, were treated with various NPs including docetaxel-loaded-TPGS- b-(PCL- ran-PGA)/PEI-endostatin NPs, and their survival time, tumor volume and body weight were monitored during regimen process. The tumor tissue histopathology was analyzed using hematoxylin and eosin staining, and microvessel density in tumor tissue was evaluated immunohistochemically. The results showed that the TPGS- b-(PCL- ran-PGA)/PEI NPs can efficiently and simultaneously deliver both coumarin-6 and plasmids into HeLa cells, and the expression of endostatin was verified via Western blot analysis. Compared with control groups, the TPGS- b-(PCL- ran-PGA)/PEI-pShuttle2-endostatin NPs significantly decreased the cell viability of HeLa cells ( p < 0.01), inhibited the growth of tumors, and even eradicated the tumors. The underlying mechanism is attributed to synergistic anti-tumor effects by the combined use of docetaxel, endostatin, and TPGS released from NPs. The TPGS- b-(PCL- ran-PGA) NPs could function as multifunctional carrier for chemotherapeutic drugs and genetic material delivery, and offer considerable potential as an ideal candidate for in vivo cancer therapy.

Qiu, Bo; Ji, Minghui; Song, Xiaosong; Zhu, Yongqiang; Wang, Zhongyuan; Zhang, Xudong; Wu, Shu; Chen, Hongbo; Mei, Lin; Zheng, Yi

2012-12-01

190

Control point analysis comparison for 3 different treatment planning and delivery complexity levels using a commercial 3-dimensional diode array.  

PubMed

To investigate the use of "Control Point Analysis" (Sun Nuclear Corporation, Melbourne, FL) to analyze and compare delivered volumetric-modulated arc therapy (VMAT) plans for 3 different treatment planning complexity levels. A total of 30 patients were chosen and fully anonymized for the purpose of this study. Overall, 10 lung stereotactic body radiotherapy (SBRT), 10 head-and-neck (H&N), and 10 prostate VMAT plans were generated on Pinnacle(3) and delivered on a Varian linear accelerator (LINAC). The delivered dose was measured using ArcCHECK (Sun Nuclear Corporation, Melbourne, FL). Each plan was analyzed using "Sun Nuclear Corporation (SNC) Patient 6" and "Control Point Analysis." Gamma passing percentage was used to assess the differences between the measured and planned dose distributions and to assess the role of various control point binning combinations. Of the different sites considered, the prostate cases reported the highest gamma passing percentages calculated with "SNC Patient 6" (97.5% to 99.2% for the 3%, 3mm) and "Control Point Analysis" (95.4% to 98.3% for the 3%, 3mm). The mean percentage of passing control point sectors for the prostate cases increased from 51.8 ± 7.8% for individual control points to 70.6 ± 10.5% for 5 control points binned together to 87.8 ± 11.0% for 10 control points binned together (2%, 2-mm passing criteria). Overall, there was an increasing trend in the percentage of sectors passing gamma analysis with an increase in the number of control points binned together in a sector for both the gamma passing criteria (2%, 2mm and 3%, 3mm). Although many plans passed the clinical quality assurance criteria, plans involving the delivery of high Monitor Unit (MU)/control point (SBRT) and plans involving high degree of modulation (H&N) showed less delivery accuracy per control point compared with plans with low MU/control point and low degree of modulation (prostate). PMID:24480374

Abdellatif, Ady; Gaede, Stewart

2014-01-01

191

Efficacy of a portable oxygen concentrator with pulsed delivery for treatment of hypoxemia during anesthesia of wildlife.  

PubMed

Portable battery-driven oxygen concentrators provide an alternative to the use of oxygen cylinders for treatment of hypoxemia during field anesthesia. The aim of this study was to evaluate the use of the EverGo Portable Oxygen Concentrator (Respironics, Murrysville, Pennsylvania 15668, USA) with pulse-dose delivery for improvement of arterial oxygenation during anesthesia of wildlife. This concentrator delivers oxygen in a pulsed flow with pulse volumes from 12 to 70 ml, up to a maximum capacity of 1.05 L/min. The pulse-dose setting shall be adjusted according to the respiratory rate of the animal, e.g., setting 6 for a respiratory rate < or = 15/min. The study included 16 free-ranging brown bears (Ursus arctos), 18 free-ranging bighorn sheep (Ovis canadensis), and five captive reindeer (Rangifer tarandus). Oxygen was administered via two nasal lines that were inserted through the nostrils to the level of the medial canthus of the eyes. Arterial blood samples were collected before, during, and after oxygen therapy and immediately analyzed. When providing oxygen from the portable concentrator, the arterial oxygenation markedly improved in all brown bears and some reindeer, whereas no or minor improvement was seen in the bighorn sheep. The mean +/- SD (range) PaO2 during oxygen supplementation was 134 +/- 29 (90-185) mmHg in the brown bears, 52 +/- 11 (32-67) mmHg in the bighorn sheep, and 79 +/- 19 (61-110) mmHg in the reindeer. The efficacy of the evaluated method may be influenced by ambient temperature, altitude, pulse-dose setting on the concentrator, the animal's respiratory rate, and species-specific physiology during anesthesia. Advantages of the portable oxygen concentrator included small size and low weight, ease of operate, and rechargeablity. PMID:22448511

Fahlman, Asa; Caulkett, Nigel; Arnemo, Jon M; Neuhaus, Peter; Ruckstuhl, Kathreen E

2012-03-01

192

Cetuximab conjugated vitamin E TPGS micelles for targeted delivery of docetaxel for treatment of triple negative breast cancers.  

PubMed

We developed a system of Cetuximab-conjugated micelles of vitamin E TPGS for targeted delivery of docetaxel as a model anticancer drug for treatment of the triple negative breast cancer (TNBC), which shows no expression of either one of the hormone progesterone receptor (PR), estrogen receptor (ER) and epidermal growth factor receptor 2 (HER2) and is thus more difficult to be treated than the positive breast cancer. Such micelles are of desired particle size, drug loading, drug encapsulation efficiency and drug release profile. Their surface morphology, surface charge and surface chemistry were also characterized. The fibroblast cells (NIH3T3), HER2 overexpressed breast cancer cells (SK-BR-3), ER and PR overexpressed breast cancer cells (MCF7), and TNBC cells of high, moderate and low EGFR expression (MDA MB 468, MDA MB 231 and HCC38) were employed to access in vitro cellular uptake of the coumarin 6 loaded TPGS micelles and cytotoxicity of docetaxel formulated in the micelles. The high IC50 value, which is the drug concentration needed to kill 50% of the cells in a designated period such as 24 h, obtained from Taxotere(®) showed that the TNBC cells are indeed more resistant to the free drug than the positive breast cancer cells. However, the therapeutic effects of docetaxel could be greatly enhanced by the formulation of Cetuximab conjugated TPGS micelles, which demonstrated 205.6 and 223.8 fold higher efficiency than Taxotere(®) for the MDA MB 468 and MDA MB 231 cell lines respectively. PMID:24090836

Kutty, Rajaletchumy Veloo; Feng, Si-Shen

2013-12-01

193

Development characterization and skin permeating potential of lipid based novel delivery system for topical treatment of psoriasis.  

PubMed

The aim of this study was to develop, optimize and evaluate the potential of solid lipid nanoparticles (SLNs) as a topical delivery system for targeted and prolonged release of Fluocinolone acetonide (FA). FA loaded SLNs were successfully developed by an emulsification-ultrasonication method and optimized using 17-run, 3-factor, 3-level Box-Behnken design of Design Expert software. SLNs were evaluated for particle size, polydispersity index, zeta potential, drug encapsulation efficiency and drug loading. Shape and surface morphology of the SLNs confirmed spherical shape of nanoparticles when investigated under a transmission electron microscope. Complete encapsulation of drug in the nanoparticles was confirmed by powder X-ray diffraction and differential scanning calorimetry. The drug release study confirmed prolonged release from the SLNs following Higuchi release kinetics with R(2) value of 0.995 where as pure drug suspension exhibited faster drug release following zero order release kinetics with R(2) value of 0.992. Stability study confirmed that SLNs were stable for 3 months at 4°C. Furthermore, in vitro skin distribution studies showed presence of significant amount of FA on the epidermal layer of skin when treated with FA loaded SLNs suspension while plain FA suspension showed minimum amount of FA in the epidermis and dermis. Moreover, selective accumulation of FA in the epidermis might eliminate adverse side effects associated with systemic exposure. Results demonstrated that FA loaded SLNs could be a promising modality for psoriasis treatment but to establish clinical utility of the present system further studies are required in clinically relevant models. PMID:25447290

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

2015-02-01

194

Routes of Delivery for CpG and Anti-CD137 for the Treatment of Orthotopic Kidney Tumors in Mice  

PubMed Central

We have found previously that the tumor cell lines, Renca (a renal cancer) and MC38 (a colon tumor) which had been injected subcutaneously in mice, could be successfully treated with a combination therapy of an oligodeoxynucleotide (CpG1826) (injected intratumorally) and anti-CD137 antibody (injected intraperitoneally). Thus the combination treatment was expected to initiate a “danger” signal via TLR9 on immune cells, and the anti-CD137 was expected to further activate T cells. In the present study, we found that several other tumor types injected subcutaneously could also be successfully treated with this combination therapy. In addition, we wished to determine if the treatment could work as effectively in an orthotopic metastatic model, which is more physiologically relevant to cancer in humans. Renca was selected as we were familiar with injecting this orthotopically into the outer cortex of the kidney in mice, and it spontaneously metastasizes to lung and abdominal sites. We tested various routes of delivery of CpG combined with intraperitoneal delivery of anti-CD137. Orthotopic tumors were injected with CpG intratumorally, using ultrasound-guided delivery on multiple occasions, combined with anti-CD137 intraperitoneally. A reduction in primary tumor size was observed following intratumoral injection of CpG compared to other treatments. We found that there was a statistically significant increase in survival of mice with orthotopic Renca tumor following intratumoral injection of CpG. However, we determined that the most effective route of delivery of CpG was intravenous, which led to further significantly enhanced survival of mice when combined with anti-CD137 intraperitoneally, likely due to inhibition of metastatic disease. Our data supports future development of this combination therapy for cancer. PMID:24788789

Westwood, Jennifer A.; Potdevin Hunnam, Titaina C. U.; Pegram, Hollie J.; Hicks, Rodney J.; Darcy, Phillip K.; Kershaw, Michael H.

2014-01-01

195

Locoregional Delivery of Adenoviral Vectors  

Microsoft Academic Search

The overall median survival of patients with a malignant glioma is ,1 y. Because malignant gliomas rarely metastasize outside the skull, locoregional treatment strategies, such as gene therapy, are under investigation. Recently, convection-enhanced delivery (CED) has been presented as a method to improve delivery of large molecules. The goal of this study was to evaluate whether CED improves intratumoral delivery

Suzanne M. Verwijnen; Eric Brouwer; Rob C. Hoeben; Marion de Jong; Bertie H. C. G. M. de Leeuw; Peter A. E. Sillevis

196

Quality assurance of serial tomotherapy for head and neck patient treatments  

Microsoft Academic Search

Purpose: A commercial serial tomotherapy intensity-modulated radiation therapy (IMRT) treatment planning (Peacock, NOMOS Corp., Sewickley, PA) and delivery system is in clinical use. The dose distributions are highly conformal, with large dose gradients often surrounding critical structures, and require accurate localization and dose delivery. Accelerator and patient-specific quality assurance (QA) procedures have been developed that address the localization, normalization, and

Daniel A Low; K. S. Clifford Chao; Sasa Mutic; Russell L Gerber; Carlos A Perez; James A Purdy

1998-01-01

197

Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation  

PubMed Central

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas. PMID:21206463

Burke, Caitlin W.; Price, Richard J.

2010-01-01

198

A magnetic mesoporous silica nanoparticle-based drug delivery system for photosensitive cooperative treatment of cancer with a mesopore-capping agent and mesopore-loaded drug  

NASA Astrophysics Data System (ADS)

Lately, there has been a growing interest in anticancer therapy with a combination of different drugs that work by different mechanisms of action, which decreases the possibility that resistant cancer cells will develop. Herein we report on the development of a drug delivery system for photosensitive delivery of a known anticancer drug camptothecin along with cytotoxic cadmium sulfide nanoparticles from a magnetic drug nanocarrier. Core-shell nanoparticles consisting of magnetic iron-oxide-cores and mesoporous silica shells are synthesized with a high surface area (859 m2 g-1) and hexagonal packing of mesopores, which are 2.6 nm in diameter. The mesopores are loaded with anticancer drug camptothecin while entrances of the mesopores are blocked with 2-nitro-5-mercaptobenzyl alcohol functionalized CdS nanoparticles through a photocleavable carbamate linkage. Camptothecin release from this magnetic drug delivery system is successfully triggered upon irradiation with UV light, as measured by fluorescence spectroscopy. Photosensitive anticancer activity of the drug delivery system is monitored by viability studies on Chinese hamster ovarian cells. The treatment of cancer cells with drug loaded magnetic material leads to a decrease in viability of the cells due to the activity of capping CdS nanoparticles. Upon exposure to low power UV light (365 nm) the loaded camptothecin is released which induces additional decrease in viability of CHO cells. Hence, the capping CdS nanoparticles and loaded camptothecin exert a cooperative anticancer activity. Responsiveness to light irradiation and magnetic activity of the nanocarrier enable its potential application for selective targeted treatment of cancer.

Kneževi?, Nikola Ž.; Lin, Victor S.-Y.

2013-01-01

199

Nanodrug-Enhanced Radiofrequency Tumor Ablation: Effect of Micellar or Liposomal Carrier on Drug Delivery and Treatment Efficacy  

PubMed Central

Purpose To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. Materials/Methods Fischer 344 rats were used (n?=?196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of IV fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4–24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm) or liposomal (100 nm) preparations of doxorubicin (Dox; targeting HIF-1?) or quercetin (Qu; targeting HSP70). Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg IV, 15 min post-RFA), and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg IV). Tumor coagulation and HIF-1? orHSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with IV Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA) compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4–72 hr. Results Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm) and liver (100 nm) (p<0.05). Mic-Dox and Mic-Qu suppressed periablational HIF-1? or HSP70 rim thickness more than liposomal preparations (p<0.05). RFA/Mic-Dox had greater early (4 hr) intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24–72 hr post-RFA (p<0.04). No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03). Conclusion With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug accumulation over time and reduced tumor growth. Accordingly, different carriers provide specific advantages, which should be considered when formulating optimal combination therapies. PMID:25133740

Moussa, Marwan; Goldberg, S. Nahum; Kumar, Gaurav; Sawant, Rupa R.; Levchenko, Tatyana; Torchilin, Vladimir P.; Ahmed, Muneeb

2014-01-01

200

Systemic delivery of synthetic microRNA-451 is an effective therapeutic strategy for the treatment of lung cancer.  

PubMed

MicroRNAs (miRNAs) can function as tumor suppressors and may provide an efficient strategy for the eradication of cancer. Specific miRNAs can be reintroduced into tumor cells to complement loss of tumor suppression activities. The aim of the present study was to develop miRNA delivery formulation using synthesized miR-451. miR-451 was detected using RT-PCR and tissues were analyzed using immunohistochemical analysis. miRNA delivery formulation proved to be effective either locally or systemically. miR-451 accumulation became evident in tumor cells and exerted an anti-proliferative function. The intravenous delivery of formulated miR-451 did not induce any deregulation in the cytokine levels and liver enzymes. Taken together, the results provide insight into the concept of the systemic delivery of synthetic mimics for tumor suppressor miR-451 and provide potential implications for miRNA therapy in clinical practice. PMID:25812923

Lou, Baisong; Zhou, Xin

2015-05-01

201

Commissioning of an integrated platform for time-resolved treatment delivery in scanned ion beam therapy by means of optical motion monitoring.  

PubMed

The integrated use of optical technologies for patient monitoring is addressed in the framework of time-resolved treatment delivery for scanned ion beam therapy. A software application has been designed to provide the therapy control system (TCS) with a continuous geometrical feedback by processing the external surrogates tridimensional data, detected in real-time via optical tracking. Conventional procedures for phase-based respiratory phase detection were implemented, as well as the interface to patient specific correlation models, in order to estimate internal tumor motion from surface markers. In this paper, particular attention is dedicated to the quantification of time delays resulting from system integration and its compensation by means of polynomial interpolation in the time domain. Dedicated tests to assess the separate delay contributions due to optical signal processing, digital data transfer to the TCS and passive beam energy modulation actuation have been performed. We report the system technological commissioning activities reporting dose distribution errors in a phantom study, where the treatment of a lung lesion was simulated, with both lateral and range beam position compensation. The zero-delay systems integration with a specific active scanning delivery machine was achieved by tuning the amount of time prediction applied to lateral (14.61 ± 0.98 ms) and depth (34.1 ± 6.29 ms) beam position correction signals, featuring sub-millimeter accuracy in forward estimation. Direct optical target observation and motion phase (MPh) based tumor motion discretization strategies were tested, resulting in 20.3(2.3)% and 21.2(9.3)% median (IQR) percentual relative dose difference with respect to static irradiation, respectively. Results confirm the technical feasibility of the implemented strategy towards 4D treatment delivery, with negligible percentual dose deviations with respect to static irradiation. PMID:24354750

Fattori, G; Saito, N; Seregni, M; Kaderka, R; Pella, A; Constantinescu, A; Riboldi, M; Steidl, P; Cerveri, P; Bert, C; Durante, M; Baroni, G

2014-12-01

202

Evaluation of renal nerve morphological changes and norepinephrine levels following treatment with novel bipolar radiofrequency delivery systems in a porcine model  

PubMed Central

Objective: To evaluate the safety and effectiveness of different bipolar radiofrequency system algorithms in interrupting the renal sympathetic nerves and reducing renal norepinephrine in a healthy porcine model. Methods: A porcine model (N?=?46) was used to investigate renal norepinephrine levels and changes to renal artery tissues and nerves following percutaneous renal denervation with radiofrequency bipolar electrodes mounted on a balloon catheter. Parameters of the radiofrequency system (i.e. electrode length and energy delivery algorithm), and the effects of single and longitudinal treatments along the artery were studied with a 7-day model in which swine received unilateral radiofrequency treatments. Additional sets of animals were used to examine norepinephrine and histological changes 28 days following bilateral percutaneous radiofrequency treatment or surgical denervation; untreated swine were used for comparison of renal norepinephrine levels. Results: Seven days postprocedure, norepinephrine concentrations decreased proportionally to electrode length, with 81, 60 and 38% reductions (vs. contralateral control) using 16, 4 and 2-mm electrodes, respectively. Applying a temperature-control algorithm with the 4-mm electrodes increased efficacy, with a mean 89.5% norepinephrine reduction following a 30-s treatment at 68°C. Applying this treatment along the entire artery length affected more nerves vs. a single treatment, resulting in superior norepinephrine reduction 28 days following bilateral treatment. Conclusion: Percutaneous renal artery application of bipolar radiofrequency energy demonstrated safety and resulted in a significant renal norepinephrine content reduction and renal nerve injury compared with untreated controls in porcine models. PMID:24875181

Cohen-Mazor, Meital; Mathur, Prabodh; Stanley, James R.L.; Mendelsohn, Farrell O.; Lee, Henry; Baird, Rose; Zani, Brett G.; Markham, Peter M.; Rocha-Singh, Krishna

2014-01-01

203

Exploring the potential of gastro retentive dosage form in delivery of ellagic acid and aloe vera gel powder for treatment of gastric ulcers.  

PubMed

Approach of novel drug delivery system (NDDS) overcomes the limitations of conventional dosage forms. However, this concept is still not practiced to a large extent in delivery of herbal drugs in Ayurveda. Thus, the potential of herbal drugs has not been explored to its fullest. Hence, there is a growing need to amalgamate the concept of NDDS in delivery of herbal constituents. The present investigation is designed to deliver and retain two herbal constituents in stomach for better action against Helicobacter pylori induced gastric ulcers. The objective was to develop a bilayer floating tablet of ellagic acid and Aloe vera gel powder through rational combination of excipients to give the lowest possible lag time with maximum drug release in the period of 4 h. Formulation F9 containing 100 mg of HPMC K15M, 27 mg of crospovidone, 80 mg of mannitol and effervescent agents in the ratio 1:2 gave 92% drug release and desired floating properties. In vivo studies showed that combination of ellagic acid and Aloe vera gave 75 % ulcer inhibition in comparison to 57% ulcer inhibition in the group which was administered with ellagic acid alone. This suggests the use of bilayer floating tablet in gastric ulcer treatment. PMID:24261674

Ranade, Arati N; Ranpise, Nisharani S; Ramesh, C

2014-01-01

204

The delivery of poly(lactic acid)-poly(ethylene glycol) nanoparticles loaded with non-toxic drug to overcome drug resistance for the treatment of neuroblastoma  

NASA Astrophysics Data System (ADS)

Neuroblastoma is a rare cancer of the sympathetic nervous system. A neuroblastoma tumor develops in the nerve tissue and is diagnosed in infants and children. Approximately 10.2 per million children under the age of 15 are affected in the United States and is slightly more common in boys. Neuroblastoma constitutes 6% of all childhood cancers and has a long-term survival rate of only 15%. There are approximately 700 new cases of neuroblastoma each year in the United States. With such a low rate of survival, the development of more effective treatment methods is necessary. A number of therapies are available for the treatment of these tumors; however, clinicians and their patients face the challenges of systemic side effects and drug resistance of the tumor cells. The application of nanoparticles has the potential to provide a safer and more effective method of delivery drugs to tumors. The advantage of using nanoparticles for drug delivery is the ability to specifically or passively target tumors while reducing the harmful side effects of chemotherapeutics. Drug delivery via nanoparticles can also allow for lower dosage requirements with controlled release of the drugs, which can further reduce systemic toxicity. The aim of this research was to develop a polymeric nanoparticle drug delivery system for the treatment of high-risk neuroblastoma. Nanoparticles composed of a poly(lactic acid)-poly(ethylene glycol) block copolymer were formulated to deliver a non-toxic drug in combination with Temozolomide, a commonly used chemotherapeutic drug for the treatment of neuroblastoma. The non-toxic drug acts as an inhibitor to the DNA-repair protein present in neuroblastoma cells that is responsible for inducing drug resistance in the cells, which would potentially allow for enhanced temozolomide activity. A variety of studies were completed to prove the nanoparticles' low toxicity, loading abilities, and uptake into cells. Additionally, studies were performed to determine the individual effect on cell toxicity of each drug and in combination. Finally, nanoparticles were loaded with the non-toxic drug and delivered with free temozolomide to determine the overall efficacy of the drugs in reducing neuroblastoma cell viability.

Dhulekar, Jhilmil

205

Development and testing of gold nanoparticles for drug delivery and treatment of heart failure: a theranostic potential for PPP cardiology  

PubMed Central

Introduction Nanoscale gold particles (AuNPs) have wide perspectives for biomedical applications because of their unique biological properties, as antioxidative activity and potentials for drug delivery. Aims and objectives The aim was to test effects of AuNPs using suggested heart failure rat model to compare with proved medication Simdax, to test gold nanoparticle for drug delivery, and to test sonoporation effect to increase nanoparticles delivery into myocardial cells. Material and methods We performed biosafety and biocompatibility tests for AuNPs and conjugate with Simdax. For in vivo tests, we included Wistar rats weighing 180–200 g (n = 54), received doxorubicin in cumulative dose of 12.0 mg/kg to model advance heart failure, registered by ultrasonography. We formed six groups: the first three groups of animals received, respectively, 0.06 ml Simdax, AuNPs, and conjugate (AuNPs-Simdax), intrapleurally, and the second three received them intravenously. The seventh group was control (saline). We performed dynamic assessment of heart failure regression in vivo measuring hydrothorax. Sonoporation of gold nanoparticles to cardiomyocytes was tested. Results We designed and constructed colloidal, spherical gold nanoparticles, AuNPs-Simdax conjugate, both founded biosafety (in cytotoxicity, genotoxicity, and immunoreactivity). In all animals of the six groups after the third day post-medication injection, no ascites and liver enlargement were registered (P < 0.001 vs controls). Conjugate injection showed significantly higher hydrothorax reduction than Simdax injection only (P < 0.01); gold nanoparticle injection showed significantly higher results than Simdax injection (P < 0.05). AuNPs and conjugate showed no significant difference for rat recovery. Difference in rat life continuity was significant between Simdax vs AuNPs (P < 0.05) and Simdax vs conjugate (P < 0.05). Sonoporation enhances AuNP transfer into the cell and mitochondria that were highly localized, superior to controls (P < 0.01 for both). Conclusions Gold nanoparticles of 30 nm and its AuNPs-Simdax conjugate gave positive results in biosafety and biocompatibility in vitro and in vivo. AuNPs-Simdax and AuNPs have similar significant cardioprotective effects in rats with doxorubicin-induced heart failure, higher than that of Simdax. Intrapleural (local) delivery is preferred over intravenous (systemic) delivery according to all tested parameters. Sonoporation is able to enhance gold nanoparticle delivery to myocardial cells in vivo. PMID:23889805

2013-01-01

206

SU-E-J-81: Interplay Effect in Non-Gated Dynamic Treatment Delivery of a Lung Phantom with Simulated Respiratory Motion  

SciTech Connect

Purpose: To quantify the interplay effect in non-gated VMAT external beam delivery using realistic, clinically relevant 3D motion in an anthropomorphic lung phantom, and to determine if adding margins is sufficient to account for motion or if gating is required in all cases. Methods: A 4D motion stage was used to move a Virtual Water (VW) lung target containing a piece of radiochromic EBT3 film in an anthropomorphic chest phantom. A five-arc stereotactic body radiation therapy (SBRT) treatment was planned using a CT scan of the phantom in its stationary position, using planning parameters chosen to push the optimizer to achieve a highly-modulated plan. Two scenarios were delivered using a Varian TrueBeam: the first was delivered with the phantom and target both stationary and the second was delivered with the phantom stationary but the target moving in a realistic, irregular 3D elliptical pattern. A single piece of 4×4 cm{sup 2} film was used per fraction, located in the central coronal plane of the target. Film was calibrated on a 6 MV beam with dose values from 0.20 to 20 Gy. Results: Preliminary test films were analyzed in ImageJ and MatLab software. Dose maps were calculated on a central region of interest (ROI) delineated on both the motion-induced and stationary films. Both static and dynamic film dose maps agreed with planning values within acceptable uncertainty. Conclusion: Including a large number of arcs in a clinically realistic SBRT treatment could reduce the effect of motion interplay due to averaging. Because all clinics do not employ multiple arcs for SBRT lung treatments, it is still important to consider the effects of motion on treatment delivery. Further analysis on the treatment films, as well as a broader investigation other planning parameters, will be conducted.

Desai, V; Fagerstrom, J; Bayliss, A; Kissick, M [University of Wisconsin, Madison, WI (United States)

2014-06-01

207

Poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) nanoparticles for local delivery of paclitaxel for restenosis treatment  

Microsoft Academic Search

Catheter-based local delivery of biodegradable nanoparticles (NP) with sustained release characteristics represents a therapeutic approach to reduce restenosis. Paclitaxel-loaded NP consisting of poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) (PVA-g-PLGA) with varying PLGA chain length as well as poly(lactide-co-glycolide) (PLGA), were prepared by a solvent evaporation technique. NP of <180 nm in diameter characterized by photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and atomic force

Ulrich Westedt; Marc Kalinowski; Matthias Wittmar; Thomas Merdan; Florian Unger; Jutta Fuchs; Susann Schäller; Udo Bakowsky; Thomas Kissel

2007-01-01

208

Nanoclays for polymer nanocomposites, paints, inks, greases and cosmetics formulations, drug delivery vehicle and waste water treatment  

Microsoft Academic Search

An overview of nanoclays or organically modified layered silicates (organoclays) is presented with emphasis placed on the\\u000a use of nanoclays as the reinforcement phase in polymer matrices for preparation of polymer\\/layered silicates nanocomposites,\\u000a rheological modifier for paints, inks and greases, drug delivery vehicle for controlled release of therapeutic agents, and\\u000a nanoclays for industrial waste water as well as potable water

Hasmukh A. Patel; Rajesh S. Somani; Hari C. Bajaj; Raksh V. Jasra

2006-01-01

209

Developing an effective therapeutic by delivery of synthetic microRNA-520e in lung cancer treatment.  

PubMed

MicroRNAs (miRNAs) can function as tumor suppressors and might provide an efficient strategy for annihilating cancer. Specific miRNAs can be reintroduced into tumor cells to complement the loss of tumor suppression activities. The "miRNA replacement therapy" is based on the concept that the reintroduction of miRNAs depleted in cancer cells reactivates cellular pathways that lead to therapeutic responses. Here, we report the development of miRNA delivery formulation using synthesized miR-520e. This formulation proved to be effective either locally or systematically. MiR-520e accumulation becomes evident in tumor cells and then exerts anti-proliferative function. Meanwhile, intravenous delivery of formulated miR-520e does not induce any deregulation in cytokine levels and liver enzymes. Taken together, our results shed new lights on the concept that systematic delivery of synthetic mimics for tumor suppressor miR-520e and provide potential implications for miRNA therapy in clinic. PMID:25661366

Ma, Dedong; Lu, Hongxiu; Qu, Yiqing; Fu, Weijiang; Ma, Zhe

2015-02-01

210

Fractional carbon dioxide laser-assisted drug delivery of topical timolol solution for the treatment of deep infantile hemangioma: a pilot study.  

PubMed

Infantile hemangiomas (IHs) are benign vascular tumors of infancy. Topical timolol has recently been reported to be an effective treatment for superficial IHs, although it failed to have an effect on deep IHs. This prospective study was aimed at evaluating the feasibility of ablative fractional laser-assisted drug delivery for enhancing topical timolol permeation into deep IHs. Nine patients ages 1 to 6 months with deep IHs were enrolled. A fractional carbon dioxide (CO2 ) laser system was applied to the skin surface of deep IHs using the DeepFx mode (25-30 mJ/pulse, 5% density, single pulse) at 1-week intervals. Topical timolol maleate 0.5% ophthalmic solution was applied under occlusion for 30 minutes four to five times per day for an average treatment duration of 14.2 weeks. Clinical improvement was evaluated according to a global score and the Hemangioma Activity Score (HAS). Four patients (44.4%) demonstrated excellent regression, four (44.4%) showed good response, and one (11.1%) experienced moderate regression. The HAS declined from 4.1 ± 0.7 at baseline to 1.7 ± 0.7 at 1 week (p < 0.001) and 1.4 ± 0.7 at 3 months (p = 0.03) after the last treatment procedure. Plasma timolol concentration was not detected in any of the patients after the first administration of topical timolol. No systemic complication or skin side effects were observed in any of the patients. Ablative fractional laser-assisted transdermal delivery of topical timolol is a safe and effective method for the treatment of deep IHs. PMID:24602019

Ma, Gang; Wu, Pinru; Lin, Xiaoxi; Chen, Hui; Hu, Xiaojie; Jin, Yunbo; Qiu, Yajing

2014-01-01

211

Enhanced delivery of topically-applied formulations following skin pre-treatment with a hand-applied, plastic microneedle array.  

PubMed

The purpose of this work is to characterize microchannels created by polymeric microneedles, applied by hand, and to demonstrate enhanced delivery of topically applied formulations of lidocaine hydrochloride and methylprednisolone sodium succinate (MPSS). 3M's Microstructured Transdermal System (MTS) arrays were applied to domestic swine to demonstrate reliability of penetration, depth of penetration and durability of the structures to repeat application and high force. Tissue levels of lidocaine and MPSS following topical application with and without microneedle pretreatment were determined by HPLC-MS analysis following digestion of biopsies. Almost all microneedles penetrate the stratum corneum upon hand force application. The depth of penetration varies from <100µm to nearly 150µm depending on the application force and the firmness of the underlying tissue. The arrays show excellent durability to repeated in-vivo application, with less than 5% of the structures evidencing even minimal tip bending after 16 applications. Under extreme force against a rigid surface, the microneedles bend but do not break. A lidocaine hydrochloride formulation applied topically in-vivo showed ~340% increase in local tissue levels when the MTS arrays were used to twice pre-treat the skin prior to applying the drug. Local delivery of a topically applied formulation of MPSS was over one order of magnitude higher when the application site was twice pre-treated with the MTS array. 3M's MTS array (marketed as 3M(TM) Microchannel Skin System) provides repeatable and robust penetration of the stratum corneum and epidermis and enhances delivery of some formulations such as lidocaine hydrochloride. PMID:21696356

Duan, Dan; Moeckly, Craig; Gysbers, Jerry; Novak, Chris; Prochnow, Gayatri; Siebenaler, Kris; Albers, Leila; Hansen, Kris

2011-09-01

212

Inhalable Antibiotic Delivery Using a Dry Powder Co-delivering Recombinant Deoxyribonuclease and Ciprofloxacin for Treatment of Cystic Fibrosis  

Microsoft Academic Search

Purpose  To achieve efficient antibiotic delivery to the cystic fibrosis (CF) airway using a single inhalable powder co-encapsulating\\u000a a mucolytic and an antibiotic.\\u000a \\u000a \\u000a \\u000a Methods  Inhalable dry powders containing deoxyribonuclease and\\/or ciprofloxacin (DNase, Cipro, and DNase\\/Cipro powders) were produced\\u000a by spray-drying with dipalmitylphosphatidylcholine, albumin, and lactose as excipients, and their antibacterial effects were\\u000a evaluated using the artificial sputum model.\\u000a \\u000a \\u000a \\u000a Results  All powders showed mass

Yan Yang; Michael D. Tsifansky; Chia-Jung Wu; Hae In Yang; Gudrun Schmidt; Yoon Yeo

2010-01-01

213

Delivery of berberine using chitosan/fucoidan-taurine conjugate nanoparticles for treatment of defective intestinal epithelial tight junction barrier.  

PubMed

Bacterial-derived lipopolysaccharides (LPS) can cause defective intestinal barrier function and play an important role in the development of inflammatory bowel disease. In this study, a nanocarrier based on chitosan and fucoidan was developed for oral delivery of berberine (Ber). A sulfonated fucoidan, fucoidan-taurine (FD-Tau) conjugate, was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy. The FD-Tau conjugate was self-assembled with berberine and chitosan (CS) to form Ber-loaded CS/FD-Tau complex nanoparticles with high drug loading efficiency. Berberine release from the nanoparticles had fast release in simulated intestinal fluid (SIF, pH 7.4), while the release was slow in simulated gastric fluid (SGF, pH 2.0). The effect of the berberine-loaded nanoparticles in protecting intestinal tight-junction barrier function against nitric oxide and inflammatory cytokines released from LPS-stimulated macrophage was evaluated by determining the transepithelial electrical resistance (TEER) and paracellular permeability of a model macromolecule fluorescein isothiocyanate-dextran (FITC-dextran) in a Caco-2 cells/RAW264.7 cells co-culture system. Inhibition of redistribution of tight junction ZO-1 protein by the nanoparticles was visualized using confocal laser scanning microscopy (CLSM). The results suggest that the nanoparticles may be useful for local delivery of berberine to ameliorate LPS-induced intestinal epithelia tight junction disruption, and that the released berberine can restore barrier function in inflammatory and injured intestinal epithelial. PMID:25421323

Wu, Shao-Jung; Don, Trong-Ming; Lin, Cheng-Wei; Mi, Fwu-Long

2014-11-01

214

Delivery of Berberine Using Chitosan/Fucoidan-Taurine Conjugate Nanoparticles for Treatment of Defective Intestinal Epithelial Tight Junction Barrier  

PubMed Central

Bacterial-derived lipopolysaccharides (LPS) can cause defective intestinal barrier function and play an important role in the development of inflammatory bowel disease. In this study, a nanocarrier based on chitosan and fucoidan was developed for oral delivery of berberine (Ber). A sulfonated fucoidan, fucoidan-taurine (FD-Tau) conjugate, was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy. The FD-Tau conjugate was self-assembled with berberine and chitosan (CS) to form Ber-loaded CS/FD-Tau complex nanoparticles with high drug loading efficiency. Berberine release from the nanoparticles had fast release in simulated intestinal fluid (SIF, pH 7.4), while the release was slow in simulated gastric fluid (SGF, pH 2.0). The effect of the berberine-loaded nanoparticles in protecting intestinal tight-junction barrier function against nitric oxide and inflammatory cytokines released from LPS-stimulated macrophage was evaluated by determining the transepithelial electrical resistance (TEER) and paracellular permeability of a model macromolecule fluorescein isothiocyanate-dextran (FITC-dextran) in a Caco-2 cells/RAW264.7 cells co-culture system. Inhibition of redistribution of tight junction ZO-1 protein by the nanoparticles was visualized using confocal laser scanning microscopy (CLSM). The results suggest that the nanoparticles may be useful for local delivery of berberine to ameliorate LPS-induced intestinal epithelia tight junction disruption, and that the released berberine can restore barrier function in inflammatory and injured intestinal epithelial. PMID:25421323

Wu, Shao-Jung; Don, Trong-Ming; Lin, Cheng-Wei; Mi, Fwu-Long

2014-01-01

215

Redox-responsive targeted gelatin nanoparticles for delivery of combination wt-p53 expressing plasmid DNA and gemcitabine in the treatment of pancreatic cancer  

PubMed Central

Background Pancreatic adenocarcinoma is one of the most dreaded cancers with very low survival rate and poor prognosis to the existing frontline chemotherapeutic drugs. Gene therapy in combination with a cytotoxic agent could be a promising approach to circumvent the limitations of previously attempted therapeutic interventions. Method We have developed a redox-responsive thiolated gelatin based nanoparticle system that efficiently delivers its payload in the presence of glutathione-mediated reducing intra-cellular environment and could be successfully used for site-specific wt-p53 expressing plasmid DNA as well as gemcitabine delivery by targeting epidermal growth factor receptor (EGFR). Efficacy studies were performed in subcutaneous human adenocarcinoma bearing SCID beige mice along with molecular level p53 plasmid and apoptotic marker expression by PCR and western blot for all study groups. Results Efficacy studies demonstrate an improved in vivo targeting efficiency resulting in increased transfection efficiency and tumor growth suppression. In all the treatment groups, the targeted nanoparticles showed better anti-tumor activity than their non-targeted as well as non-encapsulated, naked therapeutic agent counterparts (50.1, 61.7 and 77.3% tumor regression by p53 plasmid alone, gemcitabine alone and in combination respectively). Molecular analysis revealed a higher mRNA expression of transfected p53 gene, its corresponding protein and that the tumor cell death in all treatment groups was due to the induction of apoptotic pathways. Conclusions Gene/drug combination treatment significantly improves the therapeutic performance of the delivery system compared to the gene or drug alone treated groups. Anti-tumor activity of the thiolated gelatin loaded wt-p53 plasmid or gemcitabine-based therapy was attributed to their ability to induce cell apoptosis, which was confirmed by a marked increase in mRNA level of proapoptotic transcription factors, as well as, protein apoptotic biomarker expression and significant decrease in the anti-apoptotic transcription factors. PMID:24507760

2014-01-01

216

Intracisternal delivery of NF?B-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment  

PubMed Central

We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NF?B activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic kainic acid (KA) injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions, respectively, known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions. We show that self-complementary AAV2/9 (scAAV2/9) delivery in the adult rat cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e., cortex, hippocampus, and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF) into the brain is a limiting factor. Interestingly, AAV2/9-2YF a rationally designed capsid mutant (affecting surface tyrosines) increased gene transfer efficiency approximately fivefold. Neurons, astrocytes, and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid. Finally, after a single intracisternal injection of scAAV2/9-2YF using the NF?B-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the CD11b marker of microglial activation. These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or transgenic disease models. However, further improvements are required to enhance viral particles penetration into the brain. PMID:25520614

Bockstael, Olivier; Tenenbaum, Liliane; Dalkara, Deniz; Melas, Catherine; De Witte, Olivier; Levivier, Marc; Chtarto, Abdelwahed

2014-01-01

217

Promising practices for delivery of court-supervised substance abuse treatment: Perspectives from six high-performing California counties operating Proposition 36  

PubMed Central

Operative for nearly a decade, California's voter-initiated Proposition 36 program offers many offenders community-based substance abuse treatment in lieu of likely incarceration. Research has documented program successes and plans for replication have proliferated, yet very little is known about how the Proposition 36 program works or practices for achieving optimal program outcomes. In this article, we identify policies and practices that key stakeholders perceive to be most responsible for the successful delivery of court-supervised substance abuse treatment to offenders under Proposition 36. Data was collected via focus groups conducted with 59 county stakeholders in six high-performing counties during 2009. Discussion was informed by seven empirical indicators of program performance and outcomes and was focused on identifying and describing elements contributing to success. Program success was primarily attributed to four strategies, those that: (1) fostered program engagement, monitored participant progress, and sustained cooperation among participants; (2) cultivated buy-in among key stakeholders; (3) capitalized on the role of the court and the judge; and (4) created a setting which promoted a high-quality treatment system, utilization of existing resources, and broad financial and political support for the program. Goals and practices for implementing each strategy are discussed. Findings provide a “promising practices” resource for Proposition 36 program evaluation and improvement and inform the design and study of other similar types of collaborative justice treatment efforts. PMID:20965568

Evans, Elizabeth; Anglin, M. Douglas; Urada, Darren; Yang, Joy

2010-01-01

218

Pharmaceutical approaches to colon targeted drug delivery systems  

Microsoft Academic Search

Purpose. Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon but also for its potential for the delivery of proteins

M. K. Chourasia; S. K. Jain

219

Ex vivo bone morphogenetic protein 2 gene delivery using periodontal ligament stem cells for enhanced re-osseointegration in the regenerative treatment of peri-implantitis.  

PubMed

Peri-implantitis is a chronic inflammatory process with advanced bone loss and impaired healing potential. For peri-implantitis treatment, tissue engineering can be applied to enhance bone regeneration of peri-implant defects. This study aimed to evaluate ex vivo bone morphogenetic protein 2 (BMP2) gene delivery using canine periodontal ligament stem cells (PDLSCs) for regeneration of peri-implantitis defects. Canine PDLSCs were transduced with adenoviral vectors containing BMP2 (BMP2/PDLSCs). After peri-implantitis was induced by ligature placement in six beagle dogs, regenerative procedures were performed; hydroxyapatite (HA) particles and collagen gel with autologous canine PDLSCs (PDLSC group) or BMP2/PDLSCs (BMP/PDLSC group) or without cells (control group) were grafted into the defects and covered by an absorbable membrane. Three months later, the animals were sacrificed. In vitro, BMP2/PDLSCs showed similar levels of stem cell properties to PDLSCs, such as colony-forming efficiency and expression of MSC markers STRO-1 and CD 146. BMP2/PDLSCs produced BMP-2 until day 21 at a concentration of 4-8 ng/mL. In vivo, the BMP2/PDLSC group showed significantly more new bone formation and re-osseointegration in peri-implantitis defects compared to the other groups. In conclusion, ex vivo BMP2 gene delivery using PDLSCs enhanced new bone formation and re-osseointegration in peri-implantitis defects. PMID:24616330

Park, Shin-Young; Kim, Kyoung-Hwa; Gwak, Eun-Hye; Rhee, Sang-Hoon; Lee, Jeong-Cheol; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2015-01-01

220

Peptide and protein delivery using new drug delivery systems.  

PubMed

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

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

2013-01-01

221

Pharmacodynamic and Therapeutic Investigation of Focused Ultrasound-Induced Blood-Brain Barrier Opening for Enhanced Temozolomide Delivery in Glioma Treatment  

PubMed Central

Focused ultrasound (FUS) exposure with the presence of microbubbles has been shown to transiently open the blood-brain barrier (BBB), and thus has potential to enhance the delivery of various kinds of therapeutic agents into brain tumors. The purpose of this study was to assess the preclinical therapeutic efficacy of FUS-BBB opening for enhanced temozolomide (TMZ) delivery in glioma treatment. FUS exposure with microbubbles was delivered to open the BBB of nude mice that were either normal or implanted with U87 human glioma cells. Different TMZ dose regimens were tested, ranging from 2.5 to 25 mg/kg. Plasma and brain samples were obtained at different time-points ranging from 0.5 to 4 hours, and the TMZ concentration within samples was quantitated via a developed LC-MS/MS procedure. Tumor progression was followed with T2-MRI, and animal survival and brain tissue histology were conducted. Results demonstrated that FUS-BBB opening caused the local TMZ accumulation in the brain to increase from 6.98 to 19 ng/mg. TMZ degradation time in the tumor core was found to increase from 1.02 to 1.56 hours. Improved tumor progression and animal survival were found at different TMZ doses (up to 15% and 30%, respectively). In conclusion, this study provides preclinical evidence that FUS-BBB opening increases the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting the potential for clinical application to improve current brain tumor treatment. PMID:25490097

Liu, Hao-Li; Huang, Chiung-Yin; Chen, Ju-Yu; Wang, Hay-Yan Jack; Chen, Pin-Yuan; Wei, Kuo-Chen

2014-01-01

222

Radiofrequency hyperthermia in the palliative treatment of mucinous carcinomatosis of appendiceal origin: optimizing and monitoring heat delivery in western patients.  

PubMed

Mucinous peritoneal carcinomatosis from a primary gastrointestinal malignancy is a lethal condition that has few treatment options with the use of surgery, chemotherapy or radiation therapy. Recent advances in hyperthermia technology and in knowledge of the natural history of this disease has suggested the possible utility of hyperthermia in the application of aggressive local-regional therapy. Radiofrequency (RF) hyperthermia to the whole abdomen, to the hemithorax, or to an isolated mucinous tumour deposit obstructing the gastrointestinal tract was used in patients with disseminated mucinous adenocarcinoma of appendiceal origin. There were 228 hyperthermia treatments in 21 patients, with a median of 10 treatments per patient. The maximum number of treatments was 26, and minimum was one. For the first six hyperthermia treatments, escalating doses of deep hyperthermia (41-45 degrees C) was monitored with multiple sensor internal temperature probes and a single sensor subcutaneous temperature probe. After reaching a maximal hyperthermia treatment, this was maintained for all subsequent treatments. Initially, the maximal temperature allowed in tumour and subcutaneous tissue was 43 degrees C. After 50 hyperthermia treatments, this was changed to 45 degrees C. If disease stabilization or response was insufficient and maximal tolerable hyperthermia had been established, the frequency of treatment was increased from every 4 weeks to every 2 weeks, and escalating doses of mitomycin C at 8 mg/m2 were added to the regimen. Mitomycin C was infused during the hyperthermia treatment. For the first 165 treatments, patients were monitored just before and 10 days after hyperthermia with a complete blood count and a full battery of laboratory tests including amylase and lipase. Response was monitored by carcinoembryonic antigen assays on a monthly basis and CT scans on a 6 monthly basis. None of the 21 patients included in this study died, required intensive care, or required major surgical interventions as a result of hyperthermia treatments. One potentially life-endangering event was profound bradycardia and hypotension observed in a 76-year-old male receiving hyperthermia treatment to his right hemithorax. Two patients developed an enterocutaneous fistula (a frequent spontaneous event in this group of patients) while under treatment. No abnormal laboratory tests were observed in the first 165 hyperthermia treatments. Heat damage to normal tissue was limited to skin blisters in three patients and induration of the subcutaneous tissues in 10 patients. Skin pain on an analogue scale of 0-10 was scored by patients as a mean of 3.6 (range 0-8) before skin analgesia was routinely utilized. With anesthetic gel, the skin discomfort was greatly reduced. Prolonged abdominal pain for 4-20 days following treatment which required narcotic analgesia was seen in four patients. A complication rate of 62% was caused by the long-term indwelling temperature probe sheaths. Infection was observed in four patients, small bowel fistula in one, and dislodgement of the temperature probe sheath requiring repeat CT was necessary in seven patients. After maximal escalation of RF power in seven patients (33%), deep hyperthermia compatible with thermal destruction of tumour (> or = 43 degrees C for 45 min) was recorded in all subsequent treatments. In eight patients (38%), heat generation compatible with chemotherapy augmentation (41.5-43 degrees C) was consistently recorded. In six patients, non-therapeutic temperatures were recorded. There was no correlation of maximal tumour temperature, maximal subcutaneous tissue temperature and maximal RF power. With the use of skin anaesthetic there was no correlation of tumour temperature and the thickness of the subcutaneous layer of the skin. Progression was seen in 14 patients, and 11 of these patients died. No patients who showed disease stabilization have died with a minimum of 2 year follow-up. (ABSTRACT TRUNCATED) PMID:11001576

Sugarbaker, P H; Sugarbaker, C; Stephens, A D; Chang, D

2000-01-01

223

On-line quality assurance of rotational radiotherapy treatment delivery by means of a 2D ion chamber array and the Octavius phantom  

SciTech Connect

For routine pretreatment verification of innovative treatment techniques such as (intensity modulated) dynamic arc therapy and helical TomoTherapy, an on-line and reliable method would be highly desirable. The present solution proposed by TomoTherapy, Inc. (Madison, WI) relies on film dosimetry in combination with up to two simultaneous ion chamber point dose measurements. A new method is proposed using a 2D ion chamber array (Seven29, PTW, Freiburg, Germany) inserted in a dedicated octagonal phantom, called Octavius. The octagonal shape allows easy positioning for measurements in multiple planes. The directional dependence of the response of the detector was primarily investigated on a dual energy (6 and 18 MV) Clinac 21EX (Varian Medical Systems, Palo Alto, CA) as no fixed angle incidences can be calculated in the Hi-Art TPS of TomoTherapy. The array was irradiated from different gantry angles and with different arc deliveries, and the dose distributions at the level of the detector were calculated with the AAA (Analytical Anisotropic Algorithm) photon dose calculation algorithm implemented in Eclipse (Varian). For validation on the 6 MV TomoTherapy unit, rotational treatments were generated, and dose distributions were calculated with the Hi-Art TPS. Multiple cylindrical ion chamber measurements were used to cross-check the dose calculation and dose delivery in Octavius in the absence of the 2D array. To compensate for the directional dependence of the 2D array, additional prototypes of Octavius were manufactured with built-in cylindrically symmetric compensation cavities. When using the Octavius phantom with a 2 cm compensation cavity, measurements with an accuracy comparable to that of single ion chambers can be achieved. The complete Octavius solution for quality assurance of rotational treatments consists of: The 2D array, two octagonal phantoms (with and without compensation layer), an insert for nine cylindrical ion chambers, and a set of inserts of various tissue equivalent materials of different densities. The combination of the 2D array with the Octavius phantom proved to be a fast and reliable method for pretreatment verification of rotational treatments. Quality control of TomoTherapy patients was reduced to a total of {approx}25 min per patient.

Esch, Ann van; Clermont, Christian; Devillers, Magali; Iori, Mauro; Huyskens, Dominique P. [Clinique Ste Elisabeth, Place L. Godin 15, 5000 Namur, Belgium and 7Sigma, Kasteeldreef 2, 3150 Tildonk (Belgium); Clinique Ste Elisabeth, Place L. Godin 15, 5000 Namur (Belgium); Santa Maria Nuova Hospital, Viale Risorgimento 80, 42100 Reggio Emilia (Italy); Clinique Ste Elisabeth, Place L. Godin 15, 5000 Namur, Belgium and 7Sigma, Kasteeldreef 2, 3150 Tildonk (Belgium)

2007-10-15

224

Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer  

PubMed Central

Nearly 40% of patients with non-invasive bladder cancer will progress to invasive disease despite locally-directed therapy. Overcoming the bladder permeability barrier (BPB) is a challenge for intravesical drug delivery. Using the fluorophore coumarin (C6), we synthesized C6-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface modified with a novel cell penetrating polymer, poly(guanidinium oxanorbornene) (PGON). Addition of PGON to the NP surface improved tissue penetration by 10-fold in intravesically-treated mouse bladder and ex vivo human ureter. In addition, NP-C6-PGON significantly enhanced intracellular uptake of NPs compared to NPs without PGON. To examine biological activity, we synthesized NPs that were loaded with the histone deacetylase (HDAC) inhibitor belinostat (NP-Bel-PGON). NP-Bel-PGON exhibited a significantly lower IC50 in cultured bladder cancer cells, and sustained hyperacetylation, when compared to unencapsulated belinostat. Xenograft tumors treated with NP-Bel-PGON showed a 70% reduction in volume, and a 2.5-fold higher intratumoral acetyl-H4, when compared to tumors treated with unloaded NP-PGON. PMID:23764660

Martin, Darryl T.; Hoimes, Christopher J.; Kaimakliotis, Hristos Z.; Cheng, Christopher J.; Zhang, Ke; Liu, Jingchun; Wheeler, Marcia A.; Kelly, W. Kevin; Tew, Greg N.; Saltzman, W. Mark; Weiss, Robert M.

2013-01-01

225

Nanoparticle Delivery of Natural Products in the Prevention and Treatment of Cancers: Current Status and Future Prospects  

PubMed Central

The advent of nanotechnology has had a revolutionary impact on many aspects of 21st century life. Nanotechnology has provided an opportunity to explore new avenues that conventional technologies have been unable to make an impact on for diagnosis, prevention, and therapy of different diseases, and of cancer in particular. Entities in nanometer sizes are excellent platforms to incorporate various drugs or active materials that can be delivered effectively to the desired action site without compromising the activity of the incorporated drug or material. In particular, nanotechnology entities can be used to deliver conventional natural products that have poor solubility or a short half life. Conventional natural products used with entities in nanometer sizes enable us to solve many of the inherent problems (stability, solubility, toxicity) associated with natural products, and also provide a platform for targeted delivery to tumor sites. We recently introduced the novel concept of using nanotechnology for enhancing the outcome of chemoprevention, which we called ‘nanochemoprevention’. This idea was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the applications of nanotechnology for cancer prevention and therapy using natural products. PMID:24213123

Bharali, Dhruba J.; Siddiqui, Imtiaz A.; Adhami, Vaqar M.; Chamcheu, Jean Christopher; Aldahmash, Abdullah M.; Mukhtar, Hasan; Mousa, Shaker A.

2011-01-01

226

A Randomized, Double-Blind, Placebo-Controlled Study of Breath Powered Nasal Delivery of Sumatriptan Powder (AVP-825) in the Treatment of Acute Migraine (The TARGET Study)  

PubMed Central

Objective To evaluate the efficacy and safety of AVP-825, a drug–device combination of low-dose sumatriptan powder (22?mg loaded dose) delivered intranasally through a targeted Breath Powered device vs an identical device containing lactose powder (placebo device) in the treatment of migraine headache. Background Early treatment of migraine headaches is associated with improved outcome, but medication absorption after oral delivery may be delayed in migraineurs because of reduced gastric motility. Sumatriptan powder administered with an innovative, closed-palate, Bi-Directional, Breath Powered intranasal delivery mechanism is efficiently absorbed across the nasal mucosa and produces fast absorption into the circulation. Results from a previously conducted placebo-controlled study of AVP-825 showed a high degree of headache relief with an early onset of action (eg, 74% AVP-825 vs 38% placebo device at 1 hour, P?treatment vs placebo device (70% vs 45%, P?treatment with AVP-825 at 1 hour (19% vs 9%; P?=?.04). There were no serious adverse events (AEs), and no systemic AEs occurred in more than one patient. Chest pain or pressure was not reported, and only one patient taking AVP-825 reported mild paresthesia. No other triptan sensations were reported. Conclusions Targeted delivery of a low-dose of sumatriptan powder via a novel, closed-palate, Breath Powered, intranasal device (AVP-825) provided fast relief of moderate or severe migraine headache in adults that reached statistical significance over placebo by 30 minutes. The treatment was well tolerated with a low incidence of systemic AEs. PMID:25355310

Cady, Roger K; McAllister, Peter J; Spierings, Egilius LH; Messina, John; Carothers, Jennifer; Djupesland, Per G; Mahmoud, Ramy A

2015-01-01

227

What’s in a name? Is accurate recognition and labelling of mental disorders by young people associated with better help-seeking and treatment preferences?  

Microsoft Academic Search

Background  The possible benefits or harms of using psychiatric labels in the community have been a focus of debate for many decades.\\u000a The aim of this study was to examine associations between the accuracy of labelling of depression or psychosis by young people\\u000a aged 12–25 and their help-seeking, treatment and self-help preferences, whilst controlling for a range of potential confounding\\u000a factors.

Annemarie Wright; Anthony F. Jorm; Meredith G. Harris; Patrick D. McGorry

2007-01-01

228

Efficacy of a Combined Intracerebral and Systemic Gene Delivery Approach for the Treatment of a Severe Lysosomal Storage Disorder  

PubMed Central

Multiple sulfatase deficiency (MSD), a severe autosomal recessive disease is caused by mutations in the sulfatase modifying factor 1 gene (Sumf1). We have previously shown that in the Sumf1 knockout mouse model (Sumf1?/?) sulfatase activities are completely absent and, similarly to MSD patients, this mouse model displays growth retardation and early mortality. The severity of the phenotype makes MSD unsuitable to be treated by enzyme replacement or bone marrow transplantation, hence the importance of testing the efficacy of novel treatment strategies. Here we show that recombinant adeno-associated virus serotype 9 (rAAV9) vector injected into the cerebral ventricles of neonatal mice resulted in efficient and widespread transduction of the brain parenchyma. In addition, we compared a combined, intracerebral ventricles and systemic, administration of an rAAV9 vector encoding SUMF1 gene to the single administrations—either directly in brain, or systemic alone —in MSD mice. The combined treatment resulted in the global activation of sulfatases, near-complete clearance of glycosaminoglycans (GAGs) and decrease of inflammation in both the central nervous system (CNS) and visceral organs. Furthermore, behavioral abilities were improved by the combined treatment. These results underscore that the “combined” mode of rAAV9 vector administration is an efficient option for the treatment of severe whole-body disorders. PMID:21326216

Spampanato, Carmine; De Leonibus, Elvira; Dama, Paola; Gargiulo, Annagiusi; Fraldi, Alessandro; Sorrentino, Nicolina Cristina; Russo, Fabio; Nusco, Edoardo; Auricchio, Alberto; Surace, Enrico M; Ballabio, Andrea

2011-01-01

229

Efficacy of a combined intracerebral and systemic gene delivery approach for the treatment of a severe lysosomal storage disorder.  

PubMed

Multiple sulfatase deficiency (MSD), a severe autosomal recessive disease is caused by mutations in the sulfatase modifying factor 1 gene (Sumf1). We have previously shown that in the Sumf1 knockout mouse model (Sumf1(-/-)) sulfatase activities are completely absent and, similarly to MSD patients, this mouse model displays growth retardation and early mortality. The severity of the phenotype makes MSD unsuitable to be treated by enzyme replacement or bone marrow transplantation, hence the importance of testing the efficacy of novel treatment strategies. Here we show that recombinant adeno-associated virus serotype 9 (rAAV9) vector injected into the cerebral ventricles of neonatal mice resulted in efficient and widespread transduction of the brain parenchyma. In addition, we compared a combined, intracerebral ventricles and systemic, administration of an rAAV9 vector encoding SUMF1 gene to the single administrations-either directly in brain, or systemic alone -in MSD mice. The combined treatment resulted in the global activation of sulfatases, near-complete clearance of glycosaminoglycans (GAGs) and decrease of inflammation in both the central nervous system (CNS) and visceral organs. Furthermore, behavioral abilities were improved by the combined treatment. These results underscore that the "combined" mode of rAAV9 vector administration is an efficient option for the treatment of severe whole-body disorders. PMID:21326216

Spampanato, Carmine; De Leonibus, Elvira; Dama, Paola; Gargiulo, Annagiusi; Fraldi, Alessandro; Sorrentino, Nicolina Cristina; Russo, Fabio; Nusco, Edoardo; Auricchio, Alberto; Surace, Enrico M; Ballabio, Andrea

2011-05-01

230

Delivery Strategies in Behavioral Obesity Treatment: Comparing Type and Degree of Therapist Contact in Treating the Obese.  

ERIC Educational Resources Information Center

Relative to other treatment modalities for obesity, behavioral strategies, particularly self-control, have been established as effective means of weight loss and control. While most of the early research reported the presence of live professional therapists treating individuals or groups, more recent interest has focused on programs using little…

Balch, Philip; And Others

231

COMMUNICATION www.rsc.org/loc | Lab on a Chip A refillable microfabricated drug delivery device for treatment of ocular  

E-print Network

for treatment of ocular diseases Ronalee Lo,a Po-Ying Li,b Saloomeh Saati,c Rajat Agrawal,c Mark S. Humayuna device was demonstrated as a new approach for delivering therapeutic compounds to ocular tissue in acute the eye, and trauma to the eye resulting from invasive therapies. If left untreated, chronic retinal

Meng, Ellis

232

Uniformity of Evidence-Based Treatments in Practice? Therapist Effects in the Delivery of Cognitive Processing Therapy for PTSD  

ERIC Educational Resources Information Center

Objective: Various factors contribute to the effective implementation of evidence-based treatments (EBTs). In this study, cognitive processing therapy (CPT) was administered in a Veterans Affairs (VA) posttraumatic stress disorder (PTSD) specialty clinic in which training and supervision were provided following VA implementation guidelines. The…

Laska, Kevin M.; Smith, Tracey L.; Wislocki, Andrew P.; Minami, Takuya; Wampold, Bruce E.

2013-01-01

233

Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients.  

PubMed

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by mutations in the dystrophin gene, without curative treatment yet available. Our study provides, for the first time, the overall safety profile and therapeutic dose of a recombinant adeno-associated virus vector, serotype 8 (rAAV8) carrying a modified U7snRNA sequence promoting exon skipping to restore a functional in-frame dystrophin transcript, and injected by locoregional transvenous perfusion of the forelimb. Eighteen Golden Retriever Muscular Dystrophy (GRMD) dogs were exposed to increasing doses of GMP-manufactured vector. Treatment was well tolerated in all, and no acute nor delayed adverse effect, including systemic and immune toxicity was detected. There was a dose relationship for the amount of exon skipping with up to 80% of myofibers expressing dystrophin at the highest dose. Similarly, histological, nuclear magnetic resonance pathological indices and strength improvement responded in a dose-dependent manner. The systematic comparison of effects using different independent methods, allowed to define a minimum threshold of dystrophin expressing fibers (>33% for structural measures and >40% for strength) under which there was no clear-cut therapeutic effect. Altogether, these results support the concept of a phase 1/2 trial of locoregional delivery into upper limbs of nonambulatory DMD patients. PMID:25200009

Le Guiner, Caroline; Montus, Marie; Servais, Laurent; Cherel, Yan; Francois, Virginie; Thibaud, Jean-Laurent; Wary, Claire; Matot, Béatrice; Larcher, Thibaut; Guigand, Lydie; Dutilleul, Maeva; Domenger, Claire; Allais, Marine; Beuvin, Maud; Moraux, Amélie; Le Duff, Johanne; Devaux, Marie; Jaulin, Nicolas; Guilbaud, Mickaël; Latournerie, Virginie; Veron, Philippe; Boutin, Sylvie; Leborgne, Christian; Desgue, Diana; Deschamps, Jack-Yves; Moullec, Sophie; Fromes, Yves; Vulin, Adeline; Smith, Richard H; Laroudie, Nicolas; Barnay-Toutain, Frédéric; Rivière, Christel; Bucher, Stéphanie; Le, Thanh-Hoa; Delaunay, Nicolas; Gasmi, Mehdi; Kotin, Robert M; Bonne, Gisèle; Adjali, Oumeya; Masurier, Carole; Hogrel, Jean-Yves; Carlier, Pierre; Moullier, Philippe; Voit, Thomas

2014-11-01

234

Nanoparticle delivery of HIF1? siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer.  

PubMed

Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1? siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1? siRNA nanoparticles effectively reduced HIF1? expression, increased cell death, and significantly inhibited cell growth following photosan-mediated photodynamic therapy in cultured cells. Intravenous injection of the same nanoparticles into human SCC4 or SAS xenografted mice likewise resulted in concentrated siRNA accumulation and reduced HIF1? expression in tumor tissues. When combined with photodynamic therapy, HIF1? siRNA nanoparticles enhanced the regression in tumor size resulting in a?~40% decrease in volume after 10 days. Combination therapy was found to be substantially more effective than either HIF1? siRNA or photodynamic therapy alone. Results from caspase-3, TUNEL, and CD31 marker studies support this conclusion. Our results show the potential use of LCP nanoparticles for efficient delivery of HIF1? siRNA into tumors as part of combination therapy along with PDT in the treatment of oral squamous cell carcinoma. PMID:25596376

Chen, Wei-Hua; Lecaros, Rumwald Leo G; Tseng, Yu-Cheng; Huang, Leaf; Hsu, Yih-Chih

2015-04-01

235

Targeted co-delivery of docetaxel, cisplatin and herceptin by vitamin E TPGS-cisplatin prodrug nanoparticles for multimodality treatment of cancer.  

PubMed

We developed a nanocarrier system of herceptin-conjugated nanoparticles of d-alpha-tocopheryl-co-poly(ethylene glycol) 1000 succinate (TPGS)-cisplatin prodrug (HTCP NPs) for targeted co-delivery of cisplatin, docetaxel and herceptin for multimodality treatment of breast cancer of high human epidermal growth factor receptor 2 (HER2) overexpression. Co-polymers poly(lactic acid)-TPGS (PLA-TPGS) and carboxyl group-terminated TPGS (TPGS-COOH) were also added in the polymeric matrix to stabilize the prodrug nanoparticles and to facilitate herceptin conjugation. The HTCP NPs of high, moderate and low docetaxel versus cisplatin ratio were prepared by the nanoprecipitation method, which showed a pH-sensitive release for both anticancer drugs. The therapeutic effects of HTCP NPs were evaluated in vitro and compared with Taxotere® and cisplatin. The HTCP NPs of high docetaxel versus cisplatin ratio were found to have better efficacy than those of moderate and low docetaxel versus cisplatin ratio. The targeting effects of the HTCP NPs were demonstrated by a much lower IC50 value of 0.0201+0.00780+0.1629?g/mL of docetaxel+cisplatin+herceptin for SK-BR-3 cells, which are of high HER2 overexpression, than that of 0.225+0.0875+1.827?g/mL for NIH3T3 cells, which are of low HER2 overexpression, after 24h incubation. The same design of TPGS prodrug nanoparticles can also be applied for targeted co-delivery of other hydrophilic and hydrophobic drugs. PMID:23403395

Mi, Yu; Zhao, Jing; Feng, Si-Shen

2013-08-10

236

Oral administration of a curcumin-phospholipid delivery system for the treatment of central serous chorioretinopathy: a 12-month follow-up study  

PubMed Central

Background The therapeutic effects of Meriva®, a curcumin-phospholipid (lecithin) delivery system (formulated as Norflo® tablets), on visual acuity and retinal thickness in patients with acute and chronic central serous chorioretinopathy was previously investigated in a six-month open-label study. Methods In this follow-up study, visual acuity was again assessed by ophthalmologic evaluation and retinal thickness by optical coherence tomography (OCT). Norflo tablets were administered twice daily to patients with central serous chorioretinopathy. The study group consisted of 12 patients (total 18 eyes) who completed 12 months of follow-up. The primary endpoint was change in visual acuity before and after treatment with Norflo, and change in neuroretinal or retinal pigment epithelium detachment on OCT was the secondary endpoint. Results After 12 months of therapy, no eyes showed further reduction in visual acuity, 39% showed stabilization, and 61% showed statistically significant improvement (P = 0.0001 by Student’s t-test and P = 0.0005 by Wilcoxon signed rank test). Ninety-five percent of eyes showed a reduction in neuroretinal or retinal pigment epithelium detachment and 5% showed stabilization. The difference in retinal thickness after 12 months was statistically significant (P = 0.0001 by Student’s t-test and P = 0.0004 by Wilcoxon signed rank test). Conclusion These results, albeit preliminary, confirm our previous finding that this curcumin delivery system is effective in the management of central serous chorioretinopathy. When administered in a bioavailable formulation, curcumin is worth considering as a therapeutic agent for the management of inflammatory and degenerative eye conditions involving activation of retinal microglial cells. PMID:23723686

Mazzolani, Fabio; Togni, Stefano

2013-01-01

237

Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy  

NASA Astrophysics Data System (ADS)

In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

Hälg, R. A.; Besserer, J.; Boschung, M.; Mayer, S.; Lomax, A. J.; Schneider, U.

2014-05-01

238

4D analysis of influence of patient movement and anatomy alteration on the quality of 3D U/S-based prostate HDR brachytherapy treatment delivery  

SciTech Connect

Purpose: Modern HDR brachytherapy treatment for prostate cancer based on the 3D ultrasound (U/S) plays increasingly important role. The purpose of this study is to investigate possible patient movement and anatomy alteration between the clinical image set acquisition, made after the needle implantation, and the patient irradiation and their influence on the quality of treatment. Methods: The authors used 3D U/S image sets and the corresponding treatment plans based on a 4D-treatment planning procedure: plans of 25 patients are obtained right after the needle implantation (clinical plan is based on this 3D image set) and just before and after the treatment delivery. The authors notice the slight decrease of treatment quality with increase of time gap between the clinical image set acquisition and the patient irradiation. 4D analysis of dose-volume-histograms (DVHs) for prostate: CTV1 = PTV, and urethra, rectum, and bladder as organs at risk (OARs) and conformity index (COIN) is presented, demonstrating the effect of prostate, OARs, and needles displacement. Results: The authors show that in the case that the patient body movement/anatomy alteration takes place, this results in modification of DVHs and radiobiological parameters, hence the plan quality. The observed average displacement of needles (1 mm) and of prostate (0.57 mm) is quite small as compared with the average displacement noted in several other reports [A. A. Martinez et al., Int. J. Radiat. Oncol., Biol., Phys. 49(1), 61-69 (2001); S. J. Damore et al., Int. J. Radiat. Oncol., Biol., Phys. 46(5), 1205-1211 (2000); P. J. Hoskin et al., Radiotherm. Oncol. 68(3), 285-288 (2003); E. Mullokandov et al., Int. J. Radiat. Oncol., Biol., Phys. 58(4), 1063-1071 (2004)] in the literature. Conclusions: Although the decrease of quality of dosimetric and radiobiological parameters occurs, this does not cause clinically unacceptable changes to the 3D dose distribution, according to our clinical protocol.

Milickovic, Natasa; Mavroidis, Panayiotis; Tselis, Nikolaos; Nikolova, Iliyana; Katsilieri, Zaira; Kefala, Vasiliki; Zamboglou, Nikolaos; Baltas, Dimos [Department of Medical Physics and Engineering, Offenbach Clinic, Starkenburgring 66, 63069 Offenbach am Main (Germany); Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University (Sweden); Department of Radiation Oncology, Offenbach Clinic, Starkenburgring 66, 63069 Offenbach am Main (Germany); Department of Medical Physics and Engineering, Offenbach Clinic, Starkenburgring 66, 63069 Offenbach am Main (Germany); Department of Radiation Oncology, Offenbach Clinic, Starkenburgring 66, 63069 Offenbach am Main (Germany); Department of Medical Physics and Engineering, Offenbach Clinic, Starkenburgring 66, 63069 Offenbach am Main, Germany and Nuclear and Particle Physics Section, Physics Department, University of Athens, 15771 Athens (Greece)

2011-09-15

239

Local delivery of minocycline-loaded PEG-PLA nanoparticles for the enhanced treatment of periodontitis in dogs  

PubMed Central

Background Rapid local drug clearance of antimicrobials is a major drawback for the treatment of chronic periodontitis. In the study reported here, minocycline-loaded poly(ethylene glycol)-poly(lactic acid) nanoparticles were prepared and administered locally for long drug retention and enhanced treatment of periodontitis in dogs. Methods Biodegradable poly(ethylene glycol)-poly(lactic acid) was synthesized to prepare nanoparticles using an emulsion/solvent evaporation technique. The particle size and zeta potential of the minocycline-loaded nanoparticles (MIN-NPs) were determined by dynamic light scattering and the morphology of the nanoparticles was observed by transmission electron microscopy. The in vitro release of minocycline from MIN-NPs and in vivo pharmacokinetics of minocycline in gingival crevice fluid, after local administration of MIN-NPs in the periodontal pockets of beagle dogs with periodontitis, were investigated. The anti-periodontitis effects of MIN-NPs on periodontitis-bearing dogs were finally evaluated. Results Transmission electron microscopy examination and dynamic light scattering results revealed that the MIN-NPs had a round shape, with a mean diameter around 100 nm. The in vitro release of minocycline from MIN-NPs showed a remarkably sustained releasing characteristic. After local administration of the MIN-NPs, minocycline concentration in gingival crevice fluid decreased slowly and retained an effective drug concentration for a longer time (12 days) than Periocline®. Anti-periodontitis effects demonstrated that MIN-NPs could significantly decrease symptoms of periodontitis compared with Periocline and minocycline solution. These findings suggest that MIN-NPs might have great potential in the treatment of periodontitis. PMID:25170266

Yao, Wenxin; Xu, Peicheng; Pang, Zhiqing; Zhao, Jingjing; Chai, Zhilan; Li, Xiaoxia; Li, Huan; Jiang, Menglin; Cheng, Hongbo; Zhang, Bo; Cheng, Nengneng

2014-01-01

240

After Delivery  

MedlinePLUS

... after delivery. For many, it's a period of odd blood glucose swings. Not being able to predict ... stressed from lack of sleep, and off schedule. Odd sleep patterns increase the danger of napping through ...

241

Transdermal delivery of the in situ hydrogels of curcumin and its inclusion complexes of hydroxypropyl-?-cyclodextrin for melanoma treatment.  

PubMed

Curcumin (Cur) is a hydrophobic polyphenol with diverse pharmacological effects, especially for cancer treatment. However, its weak water solubility and stability was the major obstacle for the formulation research of Cur. The complexation of Cur and hydroxypropyl-?-cyclodextrin (HP-?-CD) was done by grinding. The increasing solubility of Cur was achieved due to complexation and the photochemical stability of Cur was improved. The inclusion of Cur could happen when two ends of Cur were embedded into the cavity of the HP-?-CD rings. The in situ hydrogels (ISGs) of Cur and its inclusion complexes were prepared using poloxamers 407 and 188 as the matrix. The extent of drug's in vitro release from the ISGs depended on the dissolution of drugs. Both of the ISGs had transdermal effect and cytotoxicity on B16-F10 cells. However, the effects of the ISGs containing Cur inclusion complexes were much higher than those of Cur ISGs because of the improved Cur solubility in the former. The cytotoxicity of Cur on melanoma cells was related to blocking of cellular proliferation in the G2/M stage followed by cellular apoptosis. The ISGs of Cur inclusion complexes are a promising formulation for melanoma treatment. PMID:24746691

Sun, Yunbo; Du, Lina; Liu, Yangpu; Li, Xin; Li, Miao; Jin, Yiguang; Qian, Xiaohong

2014-07-20

242

Chitosan and gelatin based prototype delivery systems for the treatment of oral mucositis: from material to performance in vitro.  

PubMed

In this study we developed and evaluated a prototype of an effective occlusive mucoadhesive system for prophylaxis and/or treatment of oral mucositis based on chitosan and gelatine models together with nystatin as a prophylactic agent incorporated into the formulation and investigated drug release in-vitro. Results of in vitro studies showed that chitosan and gelatine based gels posses properties that makes them excellent candidates for treatment of oral mucositis. These properties include not only the palliative effects of an occlusive dressing but also the potential for delivering therapeutic compounds with chitosan gels providing drug concentrations above their minimum inhibition concentration and extending the retention time in the oral cavity due to their bioadhesive properties. Chitosan also offers an advantage over suspensions because of its inherent antimicrobial properties. The performance of gelatin-based gels highlights the novel, non-toxic, in situ forming gelatine based hydrogel. The results of in vitro drug release experiments demonstrated that all the hydrogel showed sustained release properties. PMID:23017090

Perchyonok, V Tamara; Zhang, Shengmiao; Oberholzer, Theunis

2013-02-01

243

Prophylactic cannabinoid administration blocks the development of paclitaxel-induced neuropathic nociception during analgesic treatment and following cessation of drug delivery  

PubMed Central

Background Chemotherapeutic treatment results in chronic pain in an estimated 30-40 percent of patients. Limited and often ineffective treatments make the need for new therapeutics an urgent one. We compared the effects of prophylactic cannabinoids as a preventative strategy for suppressing development of paclitaxel-induced nociception. The mixed CB1/CB2 agonist WIN55,212-2 was compared with the cannabilactone CB2-selective agonist AM1710, administered subcutaneously (s.c.), via osmotic mini pumps before, during, and after paclitaxel treatment. Pharmacological specificity was assessed using CB1 (AM251) and CB2 (AM630) antagonists. The impact of chronic drug infusion on transcriptional regulation of mRNA markers of astrocytes (GFAP), microglia (CD11b) and cannabinoid receptors (CB1, CB2) was assessed in lumbar spinal cords of paclitaxel and vehicle-treated rats. Results Both WIN55,212-2 and AM1710 blocked the development of paclitaxel-induced mechanical and cold allodynia; anti-allodynic efficacy persisted for approximately two to three weeks following cessation of drug delivery. WIN55,212-2 (0.1 and 0.5 mg/kg/day s.c.) suppressed the development of both paclitaxel-induced mechanical and cold allodynia. WIN55,212-2-mediated suppression of mechanical hypersensitivity was dominated by CB1 activation whereas suppression of cold allodynia was relatively insensitive to blockade by either CB1 (AM251; 3 mg/kg/day s.c.) or CB2 (AM630; 3 mg/kg/day s.c.) antagonists. AM1710 (0.032 and 3.2 mg/kg /day) suppressed development of mechanical allodynia whereas only the highest dose (3.2 mg/kg/day s.c.) suppressed cold allodynia. Anti-allodynic effects of AM1710 (3.2 mg/kg/day s.c.) were mediated by CB2. Anti-allodynic efficacy of AM1710 outlasted that produced by chronic WIN55,212-2 infusion. mRNA expression levels of the astrocytic marker GFAP was marginally increased by paclitaxel treatment whereas expression of the microglial marker CD11b was unchanged. Both WIN55,212-2 (0.5 mg/kg/day s.c.) and AM1710 (3.2 mg/kg/day s.c.) increased CB1 and CB2 mRNA expression in lumbar spinal cord of paclitaxel-treated rats in a manner blocked by AM630. Conclusions and implications Cannabinoids block development of paclitaxel-induced neuropathy and protect against neuropathic allodynia following cessation of drug delivery. Chronic treatment with both mixed CB1/CB2 and CB2 selective cannabinoids increased mRNA expression of cannabinoid receptors (CB1, CB2) in a CB2-dependent fashion. Our results support the therapeutic potential of cannabinoids for suppressing chemotherapy-induced neuropathy in humans. PMID:24742127

2014-01-01

244

Nanomedicine in pulmonary delivery  

PubMed Central

The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

2009-01-01

245

Simultaneous delivery of doxorubicin and GG918 (Elacridar) by new polymer-lipid hybrid nanoparticles (PLN) for enhanced treatment of multidrug-resistant breast cancer.  

PubMed

Multidrug-resistant (MDR) cancer may be treated using combinations of encapsulated cytotoxic drugs and chemosensitizers. To optimize for the effectiveness of this combinational approach, novel polymer-lipid hybrid nanoparticle (PLN) formulations capable of delivering a cytotoxic drug, doxorubicin (Dox), a chemosensitizer, GG918, or their combination were prepared. Both acute and long-term anticancer activities of various combinations of Dox and GG918 in solution or PLN form were evaluated in a human MDR breast cancer cell line (MDA435/LCC6/MDR1) using trypan blue exclusion and clonogenic assays. Cellular Dox uptake and drug distribution within the cells were determined by fluoremetry and fluorescence microscopy. The results showed that the encapsulation efficiencies of Dox and GG918 in PLN were up to 89% and were not compromised by co-encapsulation of the two agents. Of various combinational treatment approaches, the Dox and GG918 co-encapsulated PLN formulation ((DG)n) demonstrated the greatest Dox uptake and anticancer activity to the MDR cells, while co-administration of two single-agent loaded PLN was least effective. Fluorescence microscopy indicated cellular internalization of (DG)n. These findings suggest that in addition to the total drug concentrations, the simultaneous delivery of Dox and GG918 to the same cellular location is critical in determining the therapeutic effectiveness of this anticancer drug-chemosensitizer combination. PMID:17097178

Wong, Ho Lun; Bendayan, Reina; Rauth, Andrew Mike; Wu, Xiao Yu

2006-12-01

246

Phase Composition Control of Calcium Phosphate Nanoparticles for Tunable Drug Delivery Kinetics and Treatment of Osteomyelitis. Part 1: Preparation and Drug Release  

PubMed Central

Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the CAP phase, decreasing from monocalcium phosphate to monetite to amorphous CAP and calcium pyrophosphate to hydroxyapatite. The sustained release of the two model drugs was shown to be directly relatable to the degradation rate of CAP carriers. It was demonstrated that the degradation rate of the carrier and the drug release kinetics could be made tunable within the time scale of 1–2 h for the most soluble CAP phase, monocalcium phosphate, to 1–2 years for the least soluble one, hydroxyapatite. From the standpoint of antibiotic therapy for osteomyelitis, typically lasting for six weeks, the most prospective CAP powder was amorphous CAP with its release time scale for a small organic molecule, the same category to which antibiotics belong, of 1 – 2 months under the conditions applied in our experiments. By combining these different CAP phases in various proportions, drug release profiles could be tailored to the therapeutic occasion. PMID:23115118

Uskokovi?, Vuk; Desai, Tejal A.

2012-01-01

247

Intracerebral delivery of Carboplatin in combination with either 6 MV Photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma  

PubMed Central

Background The purpose of the present study was to compare side-by-side the therapeutic efficacy of a 6-day infusion of carboplatin, followed by X-irradiation with either 6 MV photons or synchrotron X-rays, tuned above the K-edge of Pt, for treatment of F98 glioma bearing rats. Methods Carboplatin was administered intracerebrally (i.c.) to F98 glioma bearing rats over 6?days using AlzetTM osmotic pumps starting 7?days after tumor implantation. Radiotherapy was delivered in a single 15?Gy fraction on day 14 using a conventional 6 MV linear accelerator (LINAC) or 78.8?keV synchrotron X-rays. Results Untreated control animals had a median survival time (MeST) of 33?days. Animals that received either carboplatin alone or irradiation alone with either 78.8?keV or 6 MV had a MeSTs 38 and 33?days, respectively. Animals that received carboplatin in combination with X-irradiation had a MeST of?>?180?days with a 55% cure rate, irrespective of whether they were irradiated with either 78.8 KeV synchrotron X-rays or 6MV photons. Conclusions These studies have conclusively demonstrated the equivalency of i.c. delivery of carboplatin in combination with X-irradiation with either 6 MV photons or synchrotron X-rays. PMID:22992374

2012-01-01

248

Co-delivery of docetaxel and Poloxamer 235 by PLGA-TPGS nanoparticles for breast cancer treatment.  

PubMed

Multidrug resistance (MDR) is a major hurdle to the success of cancer chemotherapy. Poloxamers have been shown to reverse MDR by inhibiting the P-glycoprotein (P-gp) pump. The objective of this research is to test the feasibility of docetaxel-loaded PLGA-TPGS/Poloxamer 235 nanoparticles to overcome MDR in docetaxel-resistant human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by a modified nanoprecipitation method using PLGA-TPGS and PLGA-TPGS/Poloxamer 235 mixture, respectively. The PLGA-TPGS/Poloxamer 235 nanoparticles were of spherical shape and have a rough and porous surface. The docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles which had an average size of around 180nm with a narrow size distribution were stable, showing almost no change in particle size and surface charge during the 3-month storage period. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PLGA-TPGS/Poloxamer 235 porous nanoparticles (PPNPs) in docetaxel-resistant human breast cancer cell line, MCF-7/TXT, in comparison with PLGA-TPGS nanoparticles (PTNPs). The PLGA-TPGS/Poloxamer 235 porous nanoparticles produced significantly higher level of toxicity than both of PLGA-TPGS nanoparticle formulation and Taxotere® both in vitro and in vivo, indicating docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles have significant potential for the treatment of breast cancer. PMID:25686959

Tang, Xiaolong; Liang, Yong; Feng, Xiaojun; Zhang, Rongbo; Jin, Xu; Sun, Leilei

2015-04-01

249

Intranasal delivery of central nervous system-retargeted human mesenchymal stromal cells prolongs treatment efficacy of experimental autoimmune encephalomyelitis.  

PubMed

Treatment with mesenchymal stromal cells (MSCs) is currently of interest for a number of diseases including multiple sclerosis. MSCs are known to target inflamed tissues, but in a therapeutic setting their systemic administration will lead to few cells reaching the brain. We hypothesized that MSCs may target the brain upon intranasal administration and persist in central nervous system (CNS) tissue if expressing a CNS-targeting receptor. To demonstrate proof of concept, MSCs were genetically engineered to express a myelin oligodendrocyte glycoprotein-specific receptor. Engineered MSCs retained their immunosuppressive capacity, infiltrated into the brain upon intranasal cell administration, and were able to significantly reduce disease symptoms of experimental autoimmune encephalomyelitis (EAE). Mice treated with CNS-targeting MSCs were resistant to further EAE induction whereas non-targeted MSCs did not give such persistent effects. Histological analysis revealed increased brain restoration in engineered MSC-treated mice. In conclusion, MSCs can be genetically engineered to target the brain and prolong therapeutic efficacy in an EAE model. PMID:24588452

Fransson, Moa; Piras, Elena; Wang, Hao; Burman, Joachim; Duprez, Ida; Harris, Robert A; LeBlanc, Katarina; Magnusson, Peetra U; Brittebo, Eva; Loskog, Angelica S I

2014-07-01

250

Topical application of retinyl palmitate-loaded nanotechnology-based drug delivery systems for the treatment of skin aging.  

PubMed

The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS) with and without retinyl palmitate (RP). LCS containing polyether functional siloxane (PFS) as a surfactant, silicon glycol copolymer (SGC) as oil phase, and water in the ratios 30 : 25 : 45 and 40 : 50 : 10 with (OLS(v) = RP-loaded opaque liquid system and TLS(v) = RP-loaded transparent liquid system, respectively) and without (OLS and TLS, respectively) RP were studied. Samples were characterized using polarized light microscopy (PLM) and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging. PMID:24772430

Oliveira, Marcela B; do Prado, Alice Haddad; Bernegossi, Jéssica; Sato, Claudia S; Lourenço Brunetti, Iguatemy; Scarpa, Maria Virgínia; Leonardi, Gislaine Ricci; Friberg, Stig E; Chorilli, Marlus

2014-01-01

251

Characterization of different carbon nanotubes for the development of a mucoadhesive drug delivery system for intravesical treatment of bladder cancer.  

PubMed

In order to increase the effectiveness of therapeutics for bladder carcinoma (BCa) treatment, alternative strategies for intravesical applications are needed. The use of carbon nanotubes (CNTs) as basis for a multifunctional drug transporter is a promising possibility to combine traditional chemotherapeutics with innovative therapeutic agents such as antisense oligodeoxynucleotides or small interfering RNA. In the current study four CNT types varying in length and diameter (CNT-1, CNT-2, CNT-3, CNT-4) were synthesized and then characterized with different spectroscopic techniques. Compared to the pristine CNT-1 and CNT-3, the shortened CNT-2 and CNT-4 exhibited more defects and lower aspect ratios. To analyze their mucoadhesive properties, CNTs were exposed to mouse bladders ex vivo by using Franz diffusion cells. All four tested CNT types were able to adhere to the urothelium with a mean covering area of 5-10%. In vitro studies on UM-UC-3 and EJ28 BCa cells were conducted to evaluate the toxic potential of these CNTs. Viability and cytotoxicity assays revealed that the shortened CNT-2 and CNT-4 induced stronger inhibitory effects on BCa cells than CNT-1 and CNT-3. In conclusion, CNT-1 and CNT-3 showed the most promising properties for further optimization of a multifunctional drug transporter. PMID:25595385

Rieger, Christiane; Kunhardt, David; Kaufmann, Anika; Schendel, Darja; Huebner, Doreen; Erdmann, Kati; Propping, Stefan; Wirth, Manfred P; Schwenzer, Bernd; Fuessel, Susanne; Hampel, Silke

2015-02-20

252

Topical Application of Retinyl Palmitate-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging  

PubMed Central

The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS) with and without retinyl palmitate (RP). LCS containing polyether functional siloxane (PFS) as a surfactant, silicon glycol copolymer (SGC) as oil phase, and water in the ratios 30?:?25?:?45 and 40?:?50?:?10 with (OLSv = RP-loaded opaque liquid system and TLSv = RP-loaded transparent liquid system, respectively) and without (OLS and TLS, respectively) RP were studied. Samples were characterized using polarized light microscopy (PLM) and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging. PMID:24772430

Oliveira, Marcela B.; do Prado, Alice Haddad; Bernegossi, Jéssica; Sato, Claudia S.; Lourenço Brunetti, Iguatemy; Scarpa, Maria Virgínia; Leonardi, Gislaine Ricci; Friberg, Stig E.

2014-01-01

253

Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo: ex vivo permeation and skin irritation studies.  

PubMed

The aim of the present investigation was to evaluate microemulsion as a vehicle for dermal drug delivery and to develop microemulsion based gel (MBC) of clobetasol propionate (CP) for the effective treatment of vitiligo. D-Optimal mixture experimental design was adopted to optimize the amount of oil (X(1)), S(mix) (mixture of surfactant and cosurfactant) (X(2)) and water (X(3)) in the microemulsion. The formulations were assessed for globule size (nm) (Y(1)) and solubility of CP in microemulsion (mg/ml) (Y(2)). The microemulsion containing 3% oil, 45% S(mix) and 50% water was selected as the optimized batch (ME). The globule size and solubility of CP in ME were 18.26 nm and 36.42 mg/ml respectively. Transmission electron microscopy showed that ME globules were spherical in shape. Carbopol 934P was used to convert microemulsion containing drug into gel form without affecting its structure. Ex-vivo permeation studies showed that cumulative amount of CP permeated (Q(n)) from ME, MBC and market formulation (MFCP) at 8h after application were 53.6±2.18, 28.43±0.67 and 37.73±0.77 ?g cm(-2) respectively. MBC showed greater retention of CP in to skin layers than ME and MFCP. Skin irritation studies showed MBC to be significantly less irritating than MFCP. Photomicrographs and scanning electron micrographs of skin sections treated with MBC showed significant changes in the skin structure, which was attributed to the interaction of microemulsion components with skin resulting in permeation enhancement and retention of CP into skin layers. It was concluded that CP loaded gel could be a promising formulation for effective treatment of vitiligo. PMID:23000677

Patel, Hetal K; Barot, Bhavesh S; Parejiya, Punit B; Shelat, Pragna K; Shukla, Arunkumar

2013-02-01

254

Intracellular delivery of 2-deoxy-D-glucose into tumor cells by long-term cultivation and through swelling-activated pathways: implications for radiation treatment.  

PubMed

2-Deoxy-D-glucose (2DG), a well-known inhibitor of anaerobic glycolysis, is expected to exert cytotoxic and radiosensitizing effects. In order to test this hypothesis, the response of four tumor cell lines (U87-MG, GaMG, A549 and HT1080) to 2DG was analyzed for cell proliferation, changes in cell volume and nucleus size, as well as for radiation-induced DNA fragmentation, measured by the alkaline Comet assay. Two methods were used for loading cells with 2DG. The long-term method included cell cultivation in the presence of 5 mM 2DG for 24 h, while rapid intracellular delivery of 2DG was achieved by exposing the cells for 20 min to a hypotonic solution containing 100 mM 2DG. Irrespective of the loading method, 2DG inhibited the growth of HT1080 and A549 cells. In contrast, two glioblastoma lines (U87 and GaMG) were resistant to 2DG. In three of the four cell lines (all except HT1080), long-term treatment with 2DG reduced radiation-induced DNA fragmentation in conjunction with 2DG-mediated nucleus shrinkage (probably via chromatin condensation) in non-irradiated cells. Complementary volumetric experiments revealed the avid hypotonic uptake of 2DG by all tumor lines. Nonetheless, only HT1080 cells exhibited a significant increase in radiation-induced DNA fragmentation upon hypotonic loading with 2DG, associated with marked nucleus expansion in non-irradiated samples. Our data suggest that, dependant on cell type as well as on medium composition and tonicity, sugar treatment can induce the compaction or expansion of chromatin, thus decreasing or increasing radiation-induced DNA fragmentation. These results raise interesting questions for further studies on the mechanistic links between the sugar-modulated cell volume changes, chromatin structure and radiosensitivity of tumor and normal cells. PMID:21475878

Djuzenova, Cholpon S; Krasnyanska, Julia; Kiesel, Martin; Stingl, Lavinia; Zimmermann, Ulrich; Flentje, Michael; Sukhorukov, Vladimir L

2009-01-01

255

Malaria Risk Factors in Women on Intermittent Preventive Treatment at Delivery and Their Effects on Pregnancy Outcome in Sanaga-Maritime, Cameroon  

PubMed Central

Malaria is known to have a negative impact on pregnant women and their foetuses. The efficacy of Sulfadoxine-Pyrimethamine (SP) used for intermittent preventive treatment (IPT) is being threatened by increasing levels of resistance. This study assessed malaria risk factors in women on intermittent preventive treatment with SP (IPTp-SP) at delivery and their effects on pregnancy outcome in Sanaga-Maritime Division, Cameroon. Socio-economic and obstetrical data of mothers and neonate birth weights were documented. Peripheral blood from 201 mothers and newborns as well as placental and cord blood were used to prepare thick and thin blood films. Maternal haemoglobin concentration was measured. The overall malaria parasite prevalence was 22.9% and 6.0% in mothers and newborns respectively. Monthly income lower than 28000 FCFA and young age were significantly associated with higher prevalence of placental malaria infection (p?=?0.0048 and p?=?0.019 respectively). Maternal infection significantly increased the risk of infection in newborns (OR?=?48.4; p<0.0001). Haemoglobin concentration and birth weight were lower in infected mothers, although not significant. HIV infection was recorded in 6.0% of mothers and increased by 5-folds the risk of malaria parasite infection (OR?=?5.38, p?=?0.007). Attendance at antenatal clinic and level of education significantly influenced the utilisation of IPTp-SP (p<0.0001 and p?=?0.018 respectively). Use of SP and mosquito net resulted in improved pregnancy outcome especially in primiparous, though the difference was not significant. Malaria infection in pregnancy is common and increases the risk of neonatal malaria infection. Preventive strategies are poorly implemented and their utilization has overall reasonable effect on malaria infection and pregnancy outcome. PMID:23762446

Tonga, Calvin; Kimbi, Helen Kuokuo; Anchang-Kimbi, Judith Kuoh; Nyabeyeu, Hervé Nyabeyeu; Bissemou, Zacharie Bissemou; Lehman, Léopold G.

2013-01-01

256

Malaria risk factors in women on intermittent preventive treatment at delivery and their effects on pregnancy outcome in Sanaga-Maritime, Cameroon.  

PubMed

Malaria is known to have a negative impact on pregnant women and their foetuses. The efficacy of Sulfadoxine-Pyrimethamine (SP) used for intermittent preventive treatment (IPT) is being threatened by increasing levels of resistance. This study assessed malaria risk factors in women on intermittent preventive treatment with SP (IPTp-SP) at delivery and their effects on pregnancy outcome in Sanaga-Maritime Division, Cameroon. Socio-economic and obstetrical data of mothers and neonate birth weights were documented. Peripheral blood from 201 mothers and newborns as well as placental and cord blood were used to prepare thick and thin blood films. Maternal haemoglobin concentration was measured. The overall malaria parasite prevalence was 22.9% and 6.0% in mothers and newborns respectively. Monthly income lower than 28000 FCFA and young age were significantly associated with higher prevalence of placental malaria infection (p?=?0.0048 and p?=?0.019 respectively). Maternal infection significantly increased the risk of infection in newborns (OR?=?48.4; p<0.0001). Haemoglobin concentration and birth weight were lower in infected mothers, although not significant. HIV infection was recorded in 6.0% of mothers and increased by 5-folds the risk of malaria parasite infection (OR?=?5.38, p?=?0.007). Attendance at antenatal clinic and level of education significantly influenced the utilisation of IPTp-SP (p<0.0001 and p?=?0.018 respectively). Use of SP and mosquito net resulted in improved pregnancy outcome especially in primiparous, though the difference was not significant. Malaria infection in pregnancy is common and increases the risk of neonatal malaria infection. Preventive strategies are poorly implemented and their utilization has overall reasonable effect on malaria infection and pregnancy outcome. PMID:23762446

Tonga, Calvin; Kimbi, Helen Kuokuo; Anchang-Kimbi, Judith Kuoh; Nyabeyeu, Hervé Nyabeyeu; Bissemou, Zacharie Bissemou; Lehman, Léopold G

2013-01-01

257

Continuous Arc Rotation of the Couch Therapy for the Delivery of Accelerated Partial Breast Irradiation: A Treatment Planning Analysis  

SciTech Connect

Purpose: We present a novel form of arc therapy: continuous arc rotation of the couch (C-ARC) and compare its dosimetry with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT) for accelerated partial breast irradiation (APBI). C-ARC, like VMAT, uses a modulated beam aperture and dose rate, but with the couch, not the gantry, rotating. Methods and Materials: Twelve patients previously treated with APBI using 3D-CRT were replanned with (1) C-ARC, (2) IMRT, and (3) VMAT. C-ARC plans were designed with one medial and one lateral arc through which the couch rotated while the gantry was held stationary at a tangent angle. Target dose coverage was normalized to the 3D-CRT plan. Comparative endpoints were dose to normal breast tissue, lungs, and heart and monitor units prescribed. Results: Compared with 3D-CRT, C-ARC, IMRT, and VMAT all significantly reduced the ipsilateral breast V50% by the same amount (mean, 7.8%). Only C-ARC and IMRT plans significantly reduced the contralateral breast maximum dose, the ipsilateral lung V5Gy, and the heart V5%. C-ARC used on average 40%, 30%, and 10% fewer monitor units compared with 3D-CRT, IMRT, and VMAT, respectively. Conclusions: C-ARC provides improved dosimetry and treatment efficiency, which should reduce the risks of toxicity and secondary malignancy. Its tangent geometry avoids irradiation of critical structures that is unavoidable using the en face geometry of VMAT.

Shaitelman, Simona F.; Kim, Leonard H.; Yan Di; Martinez, Alvaro A. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Vicini, Frank A., E-mail: fvicini@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Grills, Inga S. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

2011-07-01

258

Liposome dependent delivery of S-adenosyl methionine to cells by liposomes: a potential treatment for liver disease.  

PubMed

The present study demonstrates that the nutritional supplement S-adenosyl methionine (SAMe), the primary methyl donor in mammalian cells, is delivered selectively to cells by anionic liposomes, and is, therefore, a liposome dependent drug. Contrary to our expectations, free SAMe chloride was growth inhibitory in cultured cells. The growth inhibitory potency of SAMe chloride in anionic liposomes composed of distearoylphosphatidylglycerol/cholesterol 2:1 was fivefold greater than that of free SAMe. Neutral liposomes composed of distearoylphosphatidylcholine and cholesterol did not increase the potency of the drug. An improved anionic liposome SAMe formulation was produced by use of the 1,4-butanedisulfonate salt (SD4), adding a metal chelator (EDTA), and lowering the buffer pH from pH 7.0 to pH 4.0. This formulation was 15-fold more potent than free SD4, and was active after more than 28 days at 4 degrees C. SAMe and its potential degradation products were screened for toxicity. Formaldehyde was determined to have potency similar to that of free SAMe chloride in CV1-P cells, suggesting that the growth inhibitory effects of SAMe may partly arise from the formation of formaldehyde. The cytotoxic effects of formaldehyde and the less stable forms of SAMe, (SAMe chloride and SAMe tosylate) were decreased in the presence of 3 mM GSH (IC(50) approximately 0.44 mM). The cytotoxic effects of SD4 were not reduced by GSH, suggesting that this more stable form of SAMe is not toxic through the production of formaldehyde. SD4 in anionic DSPG liposomes stimulated murine IL-6 production in RAW 264 cells at concentrations 25- to 30-fold lower than free drug. This increase in potency for IL-6 production was in keeping with the increase in potency observed in our growth inhibition experiments. These results suggest that SD4 in liposomes may be a potential treatment for acute or chronic liver failure. PMID:18642386

Wagner, Eric J; Krugner-Higby, Lisa; Heath, Timothy D

2009-02-01

259

Multiparticulate Formulation .. Approach to Colon Specific Drug Delivery: Current Perspectives  

Microsoft Academic Search

Colon specific drug delivery has gained increased importance not just for the delivery of drugs for the treatment of local diseases associated with the colon but also as potential site for the systemic delivery of therapeutic peptide and proteins. To achieve successful colon targeted drug delivery, a drug needs to be protected from degradation, release and\\/or absorption in the upper

Laila Fatima; Ali Asghar; Sajeev Chandran

260

Section 21: Drug Discovery/Delivery Pharmacokinetic Considerations of Local Drug Delivery to the Inner Ear by  

E-print Network

.Plontke@uni-tuebingen.de Although there is increasing interest in the local delivery of drugs to the inner ear by applying them1 Section 21: Drug Discovery/Delivery Pharmacokinetic Considerations of Local Drug Delivery, consequences of changes in delivery method, applied drug concentration or even small alterations in treatment

Salt, Alec N.

261

Radiation delivery system and method  

DOEpatents

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

Sorensen, Scott A. (Overland Park, KS); Robison, Thomas W. (Los Alamos, NM); Taylor, Craig M. V. (Jemez Springs, NM)

2002-01-01

262

Accurately determining inflationary perturbations  

E-print Network

Cosmic microwave anisotropy satellites promise extremely accurate measures of the amplitude of perturbations in the universe. We use a numerical code to test the accuracy of existing approximate expressions for the amplitude of perturbations produced by single-field inflation models. We find that the second-order Stewart-Lyth calculation gives extremely accurate results, typically better than one percent. We use our code to carry out an expansion about the general power-law inflation solution, providing a fitting function giving results of even higher accuracy.

Andrew R Liddle; Ian J Grivell

1997-01-08

263

GENE DELIVERY TO BONE  

PubMed Central

Gene delivery to bone is useful both as an experimental tool and as a potential therapeutic strategy. Among its advantages over protein delivery are the potential for directed, sustained and regulated expression of authentically processed, nascent proteins. Although no clinical trials have been initiated, there is a substantial pre-clinical literature documenting the successful transfer of genes to bone, and their intraosseous expression. Recombinant vectors derived from adenovirus, retrovirus and lentivirus, as well as non-viral vectors, have been used for this purpose. Both ex vivo and in vivo strategies, including gene-activated matrices, have been explored. Ex vivo delivery has often employed mesenchymal stem cells (MSCs), partly because of their ability to differentiate into osteoblasts. MSCs also have the potential to home to bone after systemic administration, which could serve as a useful way to deliver transgenes in a disseminated fashion for the treatment of diseases affecting the whole skeleton, such as osteoporosis or osteogenesis imperfecta. Local delivery of osteogenic transgenes, particularly those encoding bone morphogenetic proteins, has shown great promise in a number of applications where it is necessary to regenerate bone. These include healing large segmental defects in long bones and the cranium, as well as spinal fusion and treating avascular necrosis. PMID:22480730

Evans, C. H.

2012-01-01

264

A fast and accurate \\  

Microsoft Academic Search

We present a new ldquoshoeboxrdquo room acoustics simulator that is designed to support research into signal processing algorithms that are robust to reverberation. It is an improvement over existing room acoustics simulators because it is computationally fast, portable to many kinds of research environments, and flexible to use. The proposed simulator is also perceptually accurate because it models both specular

Steven M. Schimmel; Martin F. Müller; Norbert Dillier

2009-01-01

265

Project #15: Ravi Bellamkonda and Hongbin Han: Comparison of therapeutic efficacy of neuroprotective drugs between liposomal delivery and stereotactic simple diffusion delivery (SDD) via brain extracellular  

E-print Network

of neuroprotective drugs between liposomal delivery and stereotactic simple diffusion delivery (SDD) via brain extracellular space in the treatment of Alzheimer's disease Limited delivery of neuroprotective drugs into the central nervous system (CNS) by systemic administration has led to poor treatment efficacy. Drug delivery

Weber, Rodney

266

The use of biodosimetry to measure the UV-C dose delivered to a sphere, and implications for the commercial treatment of fruit  

Microsoft Academic Search

Commercialization of UV-C treatment of horticultural produce in order to induce beneficial responses in the produce following treatment requires both accurate dose delivery and a method of treating large quantities of produce efficiently. Furthermore, it has long been assumed that such effects require the entire surface of the horticultural commodities – typically fruit – to be exposed to UV-C. This

Matthew Akpoge Obande; Gilbert Shama

2011-01-01

267

Accurate Unlexicalized Parsing  

Microsoft Academic Search

We demonstrate that an unlexicalized PCFG can parse much more accurately than previously shown, by making use of simple, linguistically motivated state splits, which break down false independence assumptions latent in a vanilla treebank grammar. Indeed, its performance of 86.36% (LP\\/LR F PCFG models, and surprisingly close to the current state-of-the-art. This result has potential uses beyond establishing a strong

Dan Klein; Christopher D. Manning

2003-01-01

268

Pyomyositis after vaginal delivery  

PubMed Central

Pyomyositis is a purulent infection of skeletal muscle that arises from haematogenous spread, usually with abscess formation. It can develop after a transient bacteraemia of any cause. This type of infection has never been reported before in the literature after vaginal delivery. A 34-year-old woman had progressive severe pain in the left buttock and thigh and weakness in the left lower limb day 1 post spontaneous vaginal delivery. MRI showed severe oedema of the left gluteus, iliacus, piriformis and adductor muscles of the left thigh and a small fluid collection at the left hip joint. She was diagnosed with pyomyositis. She had fever of 37.9°C immediately postpartum and her risk factors for bacteraemia were a mild IV cannula-associated cellulitis and labour itself. She required prolonged treatment with antibiotics before significant clinical improvement was noted. PMID:22693277

Gaughan, Eve; Eogan, Maeve; Holohan, Mary

2011-01-01

269

In Vitro Analysis of Nanoparticulate Hydroxyapatite/Chitosan Composites as Potential Drug Delivery Platforms for the Sustained Release of Antibiotics in the Treatment of Osteomyelitis  

PubMed Central

Nanoparticulate composites of hydroxyapatite (HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one—HAp. Embedment of 5–10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, and promoted sustained-release kinetics throughout the 3 weeks of release time. The addition of chitosan to the particulate drug carrier formulation, however, reduced the antibacterial efficacy against S aureus. Excellent cell spreading and proliferation of osteoblastic MC3T3-E1 cells evidenced on microscopic conglomerates of HAp nanoparticles in vitro also markedly diminished on HAp/chitosan composites. Mitochondrial dehydrogenase activity exhibited normal values only for HAp/chitosan particle concentrations of up to 2 mg/cm2 and significantly dropped, by about 50%, at higher particle concentrations (4 and 8 mg/cm2). The gene expression of osteocalcin, a mineralization inductor, and the transcription factor Runx2 was downregulated in cells incubated in the presence of 3 mg/cm2 HAp/chitosan composite particles, whereas the expression of osteopontin, a potent mineralization inhibitor, was upregulated, further demonstrating the partially unfavorable osteoblastic cell response to the given particles. The peak in the expression of osteogenic markers paralleling the osteoblastic differentiation was also delayed most for the cell population incubated with HAp/chitosan particles. Overall, the positive effect of chitosan coating on the drug elution profile of HAp nanoparticles as carriers for the controlled delivery of antibiotics in the treatment of osteomyelitis was compensated for by the lower bacteriostatic efficiency and the comparatively unviable cell response to the composite material, especially at higher dosages. PMID:24382825

USKOKOVI?, VUK; DESAI, TEJAL A.

2014-01-01

270

Measurements of lateral penumbra for uniform scanning proton beams under various beam delivery conditions and comparison to the XiO treatment planning system  

SciTech Connect

Purpose: The main purposes of this study were to (1) investigate the dependency of lateral penumbra (80%–20% distance) of uniform scanning proton beams on various factors such as air gap, proton range, modulation width, compensator thickness, and depth, and (2) compare the lateral penumbra calculated by a treatment planning system (TPS) with measurements.Methods: First, lateral penumbra was measured using solid–water phantom and radiographic films for (a) air gap, ranged from 0 to 35 cm, (b) proton range, ranged from 8 to 30 cm, (c) modulation, ranged from 2 to 10 cm, (d) compensator thickness, ranged from 0 to 20 cm, and (e) depth, ranged from 7 to 15 cm. Second, dose calculations were computed in a virtual water phantom using the XiO TPS with pencil beam algorithm for identical beam conditions and geometrical configurations that were used for the measurements. The calculated lateral penumbra was then compared with the measured one for both the horizontal and vertical scanning magnets of our uniform scanning proton beam delivery system.Results: The results in the current study showed that the lateral penumbra of horizontal scanning magnet was larger (up to 1.4 mm for measurement and up to 1.0 mm for TPS) compared to that of vertical scanning magnet. Both the TPS and measurements showed an almost linear increase in lateral penumbra with increasing air gap as it produced the greatest effect on lateral penumbra. Lateral penumbra was dependent on the depth and proton range. Specifically, the width of lateral penumbra was found to be always lower at shallower depth than at deeper depth within the spread out Bragg peak (SOBP) region. The lateral penumbra results were less sensitive to the variation in the thickness of compensator, whereas lateral penumbra was independent of modulation. Overall, the comparison between the results of TPS with that of measurements indicates a good agreement for lateral penumbra, with TPS predicting higher values compared to measurements.Conclusions: Lateral penumbra of uniform scanning proton beams depends on air gap, proton range, compensator thickness, and depth, whereas lateral penumbra is not dependent on modulation. The XiO TPS typically overpredicted lateral penumbra compared to measurements, within 1 mm for most cases, but the difference could be up to 2.5 mm at a deep depth and large air gap.

Rana, Suresh; Zeidan, Omar; Ramirez, Eric; Rains, Michael; Gao, Junfang; Zheng, Yuanshui [Department of Medical Physics, ProCure Proton Therapy Center, Oklahoma City, Oklahoma 73142 (United States)] [Department of Medical Physics, ProCure Proton Therapy Center, Oklahoma City, Oklahoma 73142 (United States)

2013-09-15

271

Driving delivery vehicles with ultrasound.  

PubMed

Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled "Ultrasound for Drug and Gene Delivery," addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized. PMID:18479775

Ferrara, Katherine W

2008-06-30

272

Driving delivery vehicles with ultrasound ?  

PubMed Central

Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled “Ultrasound for Drug and Gene Delivery,” addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized. PMID:18479775

Ferrara, Katherine W.

2009-01-01

273

An Integrated Method for Reproducible and Accurate Image-Guided Stereotactic Cranial Irradiation of Brain Tumors Using the Small Animal Radiation Research Platform1  

PubMed Central

Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) to define tumor volumes, computed tomographic (CT) imaging for accurate treatment planning, a novel mouse immobilization system, and precise treatments delivered with the Small Animal Radiation Research Platform. We demonstrated that, in vivo, BLI correlated well with MRI for defining tumor volumes. Our novel restraint system enhanced setup reproducibility and precision, was atraumatic, and minimized artifacts on CT imaging used for treatment planning. We confirmed precise radiation delivery through immunofluorescent analysis of the phosphorylation of histone H2AX in irradiated brains and brain tumors. Assays with an intravenous near-infrared fluorescent probe confirmed that radiation of orthografts increased disruption of the tumor blood-brain barrier (BBB). This integrated model system, which facilitated delivery of precise, reproducible, stereotactic cranial RT in mice and confirmed RT's resultant histologic and BBB changes, may aid future brain tumor research. PMID:22937174

Baumann, Brian C; Benci, Joseph L; Santoiemma, Phillip P; Chandrasekaran, Sanjay; Hollander, Andrew B; Kao, Gary D; Dorsey, Jay F

2012-01-01

274

An integrated method for reproducible and accurate image-guided stereotactic cranial irradiation of brain tumors using the small animal radiation research platform.  

PubMed

Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) to define tumor volumes, computed tomographic (CT) imaging for accurate treatment planning, a novel mouse immobilization system, and precise treatments delivered with the Small Animal Radiation Research Platform. We demonstrated that, in vivo, BLI correlated well with MRI for defining tumor volumes. Our novel restraint system enhanced setup reproducibility and precision, was atraumatic, and minimized artifacts on CT imaging used for treatment planning. We confirmed precise radiation delivery through immunofluorescent analysis of the phosphorylation of histone H2AX in irradiated brains and brain tumors. Assays with an intravenous near-infrared fluorescent probe confirmed that radiation of orthografts increased disruption of the tumor blood-brain barrier (BBB). This integrated model system, which facilitated delivery of precise, reproducible, stereotactic cranial RT in mice and confirmed RT's resultant histologic and BBB changes, may aid future brain tumor research. PMID:22937174

Baumann, Brian C; Benci, Joseph L; Santoiemma, Phillip P; Chandrasekaran, Sanjay; Hollander, Andrew B; Kao, Gary D; Dorsey, Jay F

2012-08-01

275

Characterization of responses of 2d array seven29 detector and its combined use with octavius phantom for the patient-specific quality assurance in rapidarc treatment delivery  

SciTech Connect

A commercial 2D array seven29 detector has been characterized and its performance has been evaluated. 2D array ionization chamber equipped with 729 ionization chambers uniformly arranged in a 27 Multiplication-Sign 27 matrix with an active area of 27 Multiplication-Sign 27 cm{sup 2} was used for the study. An octagon-shaped phantom (Octavius Phantom) with a central cavity is used to insert the 2D ion chamber array. All measurements were done with a linear accelerator. The detector dose linearity, reproducibility, output factors, dose rate, source to surface distance (SSD), and directional dependency has been studied. The performance of the 2D array, when measuring clinical dose maps, was also investigated. For pretreatment quality assurance, 10 different RapidArc plans conforming to the clinical standards were selected. The 2D array demonstrates an excellent short-term output reproducibility. The long-term reproducibility was found to be within {+-}1% over a period of 5 months. Output factor measurements for the central chamber of the array showed no considerable deviation from ion chamber measurements. We found that the 2D array exhibits directional dependency for static fields. Measurement of beam profiles and wedge-modulated fields with the 2D array matched very well with the ion chamber measurements in the water phantom. The study shows that 2D array seven29 is a reliable and accurate dosimeter and a useful tool for quality assurance. The combination of the 2D array with the Octavius phantom proved to be a fast and reliable method for pretreatment verification of rotational treatments.

Syamkumar, S.A., E-mail: skppm@rediffmail.com [Department of Medical Physics, Cancer Institute (WIA), Chennai (India); Padmanabhan, Sriram; Sukumar, Prabakar; Nagarajan, Vivekanandan [Department of Medical Physics, Cancer Institute (WIA), Chennai (India)

2012-04-01

276

Challenges in the brain delivery of a promising MEK1/2 inhibitor Trametinib (Mekinist): Implications for the treatment of advanced melanoma  

E-print Network

for melanoma brain metastases. Simultaneous inhibition of multiple signaling pathways via combination therapy9/12/13 1 Challenges in the brain delivery of a promising MEK1/2 inhibitor Trametinib (Mekinist with a high propensity for brain metastasis in advanced stages. In the year 2013, it is estimated

Thomas, David D.

277

Radiotherapy delivery during motion  

NASA Astrophysics Data System (ADS)

This paper discusses the 3D dosimetric consequences of radiotherapy delivery during two kinds of motion, (i) the respiratory motion by the patient and (ii) the motion by the gantry while rotating around the patient. Respiratory motion primarily compromises treatments in the thorax and abdomen regions. Several strategies to reduce respiratory motion effects have been developed or are under development. The organ motion could for instance be measured and incorporated in the treatment planning, or adapted to by using respiratory gating and tumour-tracking delivery techniques. Gantry motion is involved in various forms of intensity-modulated arc-therapy techniques. The purpose is to increase the modulation by simultaneously varying the MLC positions, the rotation speed of the gantry, and the dose rate during the treatment. The advantage of these techniques is the increased possibility to deliver a high absorbed dose to the target volume while minimizing the dose to normal tissues. However, the dosimetric uncertainties associated with motion, small fields and steep dose gradients, has to be evaluated in detail, and this requires adequate true 3D dose-verification tools.

Ceberg, Sofie; Bäck, Sven Å. J.

2010-11-01

278

Accurate quantum chemical calculations  

NASA Technical Reports Server (NTRS)

An important goal of quantum chemical calculations is to provide an understanding of chemical bonding and molecular electronic structure. A second goal, the prediction of energy differences to chemical accuracy, has been much harder to attain. First, the computational resources required to achieve such accuracy are very large, and second, it is not straightforward to demonstrate that an apparently accurate result, in terms of agreement with experiment, does not result from a cancellation of errors. Recent advances in electronic structure methodology, coupled with the power of vector supercomputers, have made it possible to solve a number of electronic structure problems exactly using the full configuration interaction (FCI) method within a subspace of the complete Hilbert space. These exact results can be used to benchmark approximate techniques that are applicable to a wider range of chemical and physical problems. The methodology of many-electron quantum chemistry is reviewed. Methods are considered in detail for performing FCI calculations. The application of FCI methods to several three-electron problems in molecular physics are discussed. A number of benchmark applications of FCI wave functions are described. Atomic basis sets and the development of improved methods for handling very large basis sets are discussed: these are then applied to a number of chemical and spectroscopic problems; to transition metals; and to problems involving potential energy surfaces. Although the experiences described give considerable grounds for optimism about the general ability to perform accurate calculations, there are several problems that have proved less tractable, at least with current computer resources, and these and possible solutions are discussed.

Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

1989-01-01

279

Midpalmar Accurate Incision for Carpal Tunnel Release  

Microsoft Academic Search

Background: Carpal tunnel syndrome is the most common entrapment neuropathy in humans today. For patients in whom conservative treatment fails, surgical decompression is indicated. Among the various surgical techniques currently in use, endoscopic techniques are becoming increasingly popular. Due to the rapid postoperative recovery shown after endoscopic operations, midpalmar accurate incision for carpal tunnel release is a comparative alternative. Methods:

Wen-Ching Tzaan; Tai-Ngar Lui; Shih-Tseng Lee

280

COLON TARGETED DRUG DELIVERY SYSTEMS  

Microsoft Academic Search

Colon targeted drug delivery systems have the potential to deliver drugs for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. In recent years, various pharmaceutical approaches have been developed for targeting the drugs to the colon include, formation of prodrugs, coating of pH-sensitive polymers, use of colon

Ceyda Tuba

281

Electroporation-mediated gene delivery.  

PubMed

Electroporation has been used extensively to transfer DNA to bacteria, yeast, and mammalian cells in culture for the past 30 years. Over this time, numerous advances have been made, from using fields to facilitate cell fusion, delivery of chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug delivery in living tissues from rodents to man. Electroporation uses electrical fields to transiently destabilize the membrane allowing the entry of normally impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate field strengths, the application of these fields to tissues results in little, if any, damage or trauma. Indeed, electroporation has even been used successfully in human trials for gene delivery for the treatment of tumors and for vaccine development. Electroporation can lead to between 100 and 1000-fold increases in gene delivery and expression and can also increase both the distribution of cells taking up and expressing the DNA as well as the absolute amount of gene product per cell (likely due to increased delivery of plasmids into each cell). Effective electroporation depends on electric field parameters, electrode design, the tissues and cells being targeted, and the plasmids that are being transferred themselves. Most importantly, there is no single combination of these variables that leads to greatest efficacy in every situation; optimization is required in every new setting. Electroporation-mediated in vivo gene delivery has proven highly effective in vaccine production, transgene expression, enzyme replacement, and control of a variety of cancers. Almost any tissue can be targeted with electroporation, including muscle, skin, heart, liver, lung, and vasculature. This chapter will provide an overview of the theory of electroporation for the delivery of DNA both in individual cells and in tissues and its application for in vivo gene delivery in a number of animal models. PMID:25620008

Young, Jennifer L; Dean, David A

2015-01-01

282

Physically facilitating drug-delivery systems  

PubMed Central

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

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

2012-01-01

283

Pure Insulin Nanoparticle Agglomerates for Pulmonary Delivery  

E-print Network

for pulmonary delivery, using polyvinylpyrrolidone as the xcipient. 46 After spray freze-drying, the particles wer dispersd in saline solution, then ebulized and aministerd to mice as prohylactic treatment aginst Aspergilus flavus infection. Mice treatd...

Bailey, Mark Michael

2008-04-29

284

Successful treatment of osseous lesion associated with palatoradicular groove using local drug delivery and guided tissue regeneration: A report of two cases.  

PubMed

Developmental grooves are not rare and often appear on maxillary lateral and central incisors and are an important predisposing factor to localized periodontal disease. Various techniques have been adopted to eliminate the groove and regenerate lost periodontium. This report of two cases describes the technique of using the local drug delivery system with chlorehexidine and the guided tissue regeneration (GTR) to control the disease progression and regeneration. PMID:23066240

Gadagi, Jayaprakash S; Elavarasu, Sugumari; Ananda, Divya; Murugan, Thamaraiselvan

2012-08-01

285

Targeted Delivery of Proteins across the Blood-Brain Barrier  

Microsoft Academic Search

Treatment of many neuronal degenerative disorders will require delivery of a therapeutic protein to neurons or glial cells across the whole CNS. The presence of the blood-brain barrier hampers the delivery of these proteins from the blood, thus necessitating a new method for delivery. Receptors on the blood-brain barrier bind ligands to facilitate their transport to the CNS; therefore, we

Brian J. Spencer; Inder M. Verma

2007-01-01

286

Imaging evaluation of maternal complications associated with repeat cesarean deliveries.  

PubMed

The rate of cesarean deliveries continues to rise, while the rate of vaginal delivery after cesarean birth continues to decline. Many women now tend to undergo multiple cesarean deliveries, and therefore the associated chronic maternal morbidities are of growing concern. Accurate diagnosis of these conditions is crucial in maternal and fetal well-being. Many of these complications are diagnosed by imaging, and radiologists should be aware of the type and imaging appearances of these conditions. PMID:25173662

Moshiri, Mariam; Osman, Sherif; Bhargava, Puneet; Maximin, Suresh; Robinson, Tracy J; Katz, Douglas S

2014-09-01

287

Accurate spectral color measurements  

NASA Astrophysics Data System (ADS)

Surface color measurement is of importance in a very wide range of industrial applications including paint, paper, printing, photography, textiles, plastics and so on. For a demanding color measurements spectral approach is often needed. One can measure a color spectrum with a spectrophotometer using calibrated standard samples as a reference. Because it is impossible to define absolute color values of a sample, we always work with approximations. The human eye can perceive color difference as small as 0.5 CIELAB units and thus distinguish millions of colors. This 0.5 unit difference should be a goal for the precise color measurements. This limit is not a problem if we only want to measure the color difference of two samples, but if we want to know in a same time exact color coordinate values accuracy problems arise. The values of two instruments can be astonishingly different. The accuracy of the instrument used in color measurement may depend on various errors such as photometric non-linearity, wavelength error, integrating sphere dark level error, integrating sphere error in both specular included and specular excluded modes. Thus the correction formulas should be used to get more accurate results. Another question is how many channels i.e. wavelengths we are using to measure a spectrum. It is obvious that the sampling interval should be short to get more precise results. Furthermore, the result we get is always compromise of measuring time, conditions and cost. Sometimes we have to use portable syste or the shape and the size of samples makes it impossible to use sensitive equipment. In this study a small set of calibrated color tiles measured with the Perkin Elmer Lamda 18 and the Minolta CM-2002 spectrophotometers are compared. In the paper we explain the typical error sources of spectral color measurements, and show which are the accuracy demands a good colorimeter should have.

Hiltunen, Jouni; Jaeaeskelaeinen, Timo; Parkkinen, Jussi P. S.

1999-08-01

288

Alternative Applications for Drug Delivery: Nasal and Pulmonary Routes  

Microsoft Academic Search

For treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes\\u000a provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose,\\u000a several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include\\u000a liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins and others.

A. Yekta Ozer

289

Electrophoretic Particle Guidance Significantly Enhances Olfactory Drug Delivery: A Feasibility Study  

PubMed Central

Background Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and directly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has not yet been found. Methods In this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to the olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically accurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on the olfactory delivery efficiency. Findings Results showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly enhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of magnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril (i.e., partial release) led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By combining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more than 90% were observed as compared to the extremely low olfactory dosage (<1%) with conventional inhaler devices. Conclusion Results of this study have important implications in developing personalized olfactory delivery protocols for the treatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different pointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery. PMID:24497957

Xi, Jinxiang; Si, Xiuhua A.; Gaide, Rachel

2014-01-01

290

Transdermal drug delivery  

Microsoft Academic Search

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted

Mark R Prausnitz; Robert Langer

2008-01-01

291

Using In-Service and Coaching to Increase Teachers' Accurate Use of Research-Based Strategies  

ERIC Educational Resources Information Center

Increasing the accurate use of research-based practices in classrooms is a critical issue. Professional development is one of the most practical ways to provide practicing teachers with training related to research-based practices. This study examined the effects of in-service plus follow-up coaching on first grade teachers' accurate delivery of…

Kretlow, Allison G.; Cooke, Nancy L.; Wood, Charles L.

2012-01-01

292

Ocular drug delivery systems: An overview  

PubMed Central

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed. PMID:25590022

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

2014-01-01

293

Transdermal drug delivery  

PubMed Central

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

Prausnitz, Mark R.; Langer, Robert

2009-01-01

294

Targeted delivery of salicylic acid from acne treatment products into and through skin: role of solution and ingredient properties and relationships to irritation  

Microsoft Academic Search

Salicylic acid (SA) is a beta hydroxy acid and has multifunctional uses in the treatment of various diseases in skin such as acne, psoriasis, and photoaging. One problem often cited as associated with salicylic acid is that it can be quite irritating at pH 3-4, where it exhibits the highest activity in the treatment of skin diseases. We have identified

LINDA RHEIN; BHASKAR CHAUDHURI; NUR JIVANI; H. Fares; A. Davis

2004-01-01

295

An Implantable MEMS Drug Delivery Device for Rapid Delivery in Ambulatory Emergency Care  

E-print Network

We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named ...

Elman, Noel

296

Hollow hydroxyapatite microspheres/chitosan composite as a sustained delivery vehicle for rhBMP-2 in the treatment of bone defects.  

PubMed

Composite scaffold comprised of hollow hydroxyapatite (HA) and chitosan (designated hHA/CS) was prepared as a delivery vehicle for recombinating human bone morphogenetic protein-2 (rhBMP-2). The in vitro and in vivo biological activities of rhBMP2 released from the composite scaffold were then investigated. The rhBMP-2 was firstly loaded into the hollow HA microspheres, and then the rhBMP2-loaded HA microspheres were further incorporated into the chitosan matrix. The chitosan not only served to bind the HA microspheres together and kept them at the implant site, but also effectively modified the release behavior of rhBMP-2. The in vitro release and bioactivity analysis confirmed that the rhBMP2 could be loaded and released from the composite scaffolds in bioactive form. In addition, the composite scaffolds significantly reduced the initial burst release of rhBMP2, and thus providing prolonged period of time (as long as 60 days) compared with CS scaffolds. In vivo bone regenerative potential of the rhBMP2-loaded composite scaffolds was evaluated in a rabbit radius defect model. The results revealed that the rate of new bone formation in the rhBMP2-loaded hHA/CS group was higher than that in both negative control and rhBMP2-loaded CS group. These observations suggest that the hHA/CS composite scaffold would be effective and feasible as a delivery vehicle for growth factors in bone regeneration and repair. PMID:25578692

Yao, Ai-Hua; Li, Xu-Dong; Xiong, Long; Zeng, Jian-Hua; Xu, Jun; Wang, De-Ping

2015-01-01

297

Development and delivery of patient treatment in the Trondheim Hip Fracture Trial. A new geriatric in-hospital pathway for elderly patients with hip fracture  

PubMed Central

Background Hip fractures are common among frail elderly persons and often have serious consequences on function, mobility and mortality. Traditional treatment of these patients is performed in orthopedic departments without additional geriatric assessment. However, studies have shown that interdisciplinary geriatric treatment may be beneficial compared to traditional treatment. The aim of the present study is to investigate whether treatment of these patients in a Department of Geriatrics (DG) during the entire hospital stay gives additional benefits as compared to conventional treatment in a Department of Orthopaedic Surgery (DOS). Findings A new clinical pathway for in-hospital treatment of hip fracture patients was developed. In this pathway patients were treated pre-and postoperatively in DG. Comprehensive geriatric assessment was performed as an interdisciplinary, multidimensional, systematic assessment of all patients focusing on each patient’s capabilities and limitations as recommended in guidelines and systematic reviews. Identification and treatment of co-morbidities, pain relief, hydration, oxygenation, nutrition, elimination, prevention and management of delirium, assessment of falls and osteoporosis were emphasized. Discharge planning started as early as possible. Initiation of rehabilitation with focus on early mobilisation and development of individual plans was initiated in hospital and continued after discharge from hospital. Fracture specific treatment was based upon standard treatment for the hospital, expert opinions and a review of the literature. Conclusion A new treatment program for old hip fracture patients was developed, introduced and run in the DG, the potential benefits of which being compared with traditional care of hip fracture patients in the DOS in a randomised clinical trial. PMID:22800378

2012-01-01

298

A robust MRI-compatible system to facilitate highly accurate stereotactic administration of therapeutic agents to targets within the brain of a large animal model  

Microsoft Academic Search

Achieving accurate intracranial electrode or catheter placement is critical in clinical practice in order to maximise the efficacy of deep brain stimulation and drug delivery respectively as well as to minimise side-effects. We have developed a highly accurate and robust method for MRI-guided, stereotactic delivery of catheters and electrodes to deep target structures in the brain of pigs. This study

E. White; M. Woolley; A. Bienemann; D. E. Johnson; M. Wyatt; G. Murray; H. Taylor; S. S. Gill

2011-01-01

299

Routine Vaginal Delivery  

MedlinePLUS

... Friendly Doctor Delivery by Cesarean Section Choosing a School Delivery: What About the Pain? Banking Cord Blood Study Finds Over 4,500 U.S. Children Hospitalized From Child Abuse in One Year, and 300 of Them Died ...

300

Modifications in service delivery and clinical treatment for women diagnosed with severe mental illness who are also the survivors of sexual abuse trauma  

Microsoft Academic Search

Sexual abuse trauma and chronic revictimization are central to the experience of many women diagnosed with severe mental illness.\\u000a The high reported prevalence rates of sexual abuse trauma among these women necessitate that program planners and clinicians\\u000a be prepared to adapt their treatment interventions for use with trauma survivors. This article describes how current treatment\\u000a approaches for women diagnosed with

Maxine Harris

1994-01-01

301

Communication and coping as predictors of fertility problem stress: cohort study of 816 participants who did not achieve a delivery after 12 months of fertility treatment  

Microsoft Academic Search

BACKGROUND: We investigated coping strategies and communication strategies as predictors of fertility problem stress 12 months after start of ferti lity treatment. METHODS: We used a prospective, longitudinal cohort design including 2250 people beginning fertility treatment with a 12-month follow-up. Data were based on self-administered questionnaires measuring communication with partner and with other people, coping strategies: active-avoidance coping, active-confronting coping,

L. Schmidt; B. E. Holstein; U. Christensen; J. Boivin

2005-01-01

302

Magnetizable implants for targeted drug delivery  

NASA Astrophysics Data System (ADS)

The capability to deliver high effective dosages to specific sites in the human body has become the holy grail of drug delivery research. Drugs with proven effectiveness under in vitro investigation often reach a major roadblock under in vivo testing due to a lack of an effective delivery strategy. In addition, many clinical scenarios require delivery of agents that are therapeutic at the desired delivery point, but otherwise systemically toxic. This project proposes a method for targeted drug delivery by applying high magnetic field gradients within the body to an injected superparamagnetic colloidal fluid carrying a drug, with the aid of modest uniform magnetic field. The design involves patterning of endovascular implants, such as coronary stents, with soft magnetic coatings capable of applying high local magnetic field gradients within the body. Examination of the feasibility of the design has been focused around the treatment of coronary restenosis following angioplasty. Drug-eluting stents, which have debuted in hospitals over the past two years, have thus far reduced restenosis rates to below 10%. Our local drug delivery system is a viable alternative or enhancement to drug-eluting stents, offering increased clinician control of dose size, the ability to treat a site repeatedly, and a wide array of applications for treatment of other pathologies. The theoretical models, parallel plate and pipe flow analysis, and cell culture models presented give insight into the use of micron and sub-micron scale magnetic particles for site-specific delivery of pharmaceuticals and magnetically labeled cells.

Forbes, Zachary Graham

303

Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer  

PubMed Central

Star-shaped polymer micelles have good stability against dilution with water, showing promising application in drug delivery. In this work, biodegradable micelles made from star-shaped poly(å-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer were prepared and used to deliver doxorubicin (Dox) in vitro and in vivo. First, an acrylated monomethoxy poly (ethylene glycol)-poly(å-caprolactone) (MPEG-PCL) diblock copolymer was synthesized, which then self-assembled into micelles, with a core-shell structure, in water. Then, the double bonds at the end of the PCL blocks were conjugated together by radical polymerization, forming star-shaped MPEG-PCL (SSMPEG-PCL) micelles. These SSMPEG-PCL micelles were monodispersed (polydispersity index = 0.11), with mean diameter of ?25 nm, in water. Blank SSMPEG-PCL micelles had little cytotoxicity and did not induce obvious hemolysis in vitro. The critical micelle concentration of the SSMPEG-PCL micelles was five times lower than that of the MPEG-PCL micelles. Dox was directly loaded into SSMPEG-PCL micelles by a pH-induced self-assembly method. Dox loading did not significantly affect the particle size of SSMPEG-PCL micelles. Dox-loaded SSMPEG-PCL (Dox/SSMPEG-PCL) micelles slowly released Dox in vitro, and the Dox release at pH 5.5 was faster than that at pH 7.0. Also, encapsulation of Dox in SSMPEG-PCL micelles enhanced the anticancer activity of Dox in vitro. Furthermore, the therapeutic efficiency of Dox/SSMPEG-PCL on colon cancer mouse model was evaluated. Dox/SSMPEG-PCL caused a more significant inhibitory effect on tumor growth than did free Dox or controls (P < 0.05), which indicated that Dox/SSMPEG-PCL had enhanced anticolon cancer activity in vivo. Analysis with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed that Dox/SSMPEG-PCL induced more tumor cell apoptosis than free Dox or controls. These results suggested that SSMPEG-PCL micelles have promising application in doxorubicin delivery for the enhancement of anticancer effect. PMID:23493403

Gao, Xiang; Wang, BiLan; Wei, XiaWei; Rao, Wang; Ai, Fang; Zhao, Fen; Men, Ke; Yang, Bowen; Liu, Xingyu; Huang, Meijuan; Gou, Maling; Qian, ZhiYong; Huang, Ning; Wei, Yuquan

2013-01-01

304

Temporal characterization and in vitro comparison of cell survival following the delivery of 3D-conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)  

NASA Astrophysics Data System (ADS)

A phantom was designed and implemented for the delivery of treatment plans to cells in vitro. Single beam, 3D-conformal radiotherapy (3D-CRT) plans, inverse planned five-field intensity-modulated radiation therapy (IMRT), nine-field IMRT, single-arc volumetric modulated arc therapy (VMAT) and dual-arc VMAT plans were created on a CT scan of the phantom to deliver 3 Gy to the cell layer and verified using a Farmer chamber, 2D ionization chamber array and gafchromic film. Each plan was delivered to a 2D ionization chamber array to assess the temporal characteristics of the plan including delivery time and 'cell's eye view' for the central ionization chamber. The effective fraction time, defined as the percentage of the fraction time where any dose is delivered to each point examined, was also assessed across 120 ionization chambers. Each plan was delivered to human prostate cancer DU-145 cells and normal primary AGO-1522b fibroblast cells. Uniform beams were delivered to each cell line with the delivery time varying from 0.5 to 20.54 min. Effective fraction time was found to increase with a decreasing number of beams or arcs. For a uniform beam delivery, AGO-1552b cells exhibited a statistically significant trend towards increased survival with increased delivery time. This trend was not repeated when the different modulated clinical delivery methods were used. Less sensitive DU-145 cells did not exhibit a significant trend towards increased survival with increased delivery time for either the uniform or clinical deliveries. These results confirm that dose rate effects are most prevalent in more radiosensitive cells. Cell survival data generated from uniform beam deliveries over a range of dose rates and delivery times may not always be accurate in predicting response to more complex delivery techniques, such as IMRT and VMAT.

McGarry, Conor K.; Butterworth, Karl T.; Trainor, Colman; O'Sullivan, Joe M.; Prise, Kevin M.; Hounsell, Alan R.

2011-04-01

305

Ultrasound-assisted siRNA delivery via arginine-grafted bioreducible polymer and microbubbles targeting VEGF for ovarian cancer treatment.  

PubMed

The major drawback hampering siRNA therapies from being more widely accepted in clinical practice is its insufficient accumulation at the target site mainly due to poor cellular uptake and rapid degradation in serum. Therefore, we designed a novel polymeric siRNA carrier system, which would withstand serum-containing environments and tested its performance in vitro as well as in vivo. Delivering siRNA with a system combining an arginine-grafted bioreducible polymer (ABP), microbubbles (MBs), and ultrasound technology (US) we were able to synergize the advantages each delivery system owns individually, and created our innovative siRNA-ABP-MB (SAM) complexes. SAM complexes show significantly higher siRNA uptake and VEGF protein knockdown in vitro with serum-containing media when compared to naked siRNA, and 25k-branched-polyethylenimine (bPEI) representing the current standard in nonviral gene therapy. SAM complexes activated by US are also able to improve siRNA uptake in tumor tissue resulting in decelerating tumor growth in vivo. PMID:24657947

Florinas, Stelios; Kim, Jaesung; Nam, Kihoon; Janát-Amsbury, Margit M; Kim, Sung Wan

2014-06-10

306

Accurate determination of inflationary perturbations  

E-print Network

We use a numerical code for accurate computation of the amplitude of linear density perturbations and gravitational waves generated by single-field inflation models to study the accuracy of existing analytic results based on the slow-roll approximation. We use our code to calculate the coefficient of an expansion about the exact analytic result for power-law inflation; this generates a fitting function which can be applied to all inflationary models to obtain extremely accurate results. In the appropriate limit our results confirm the Stewart--Lyth analytic second-order calculation, and we find that their results are very accurate for inflationary models favoured by current observational constraints.

Ian J Grivell; Andrew R Liddle

1996-07-18

307

Accurate Monitor 1.2  

NSDL National Science Digital Library

With many computer users developing their own Web sites, some of them may be interested in monitoring how search engines may be ranking their site. This latest edition of Accurate Monitor may prove useful, as it allows individuals to find the position of their Web site in search engines like Altavista and Google. Additionally, Accurate Monitor can generate advanced statistics and monitor plugins, along with providing a flexible interface system. This version of Accurate Monitor is compatible with all systems running Windows 95 and higher.

308

Colon Targeted Drug Delivery Systems: A Review on Primary and Novel Approaches  

Microsoft Academic Search

The colon is a site where both local and systemic delivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific Drug Delivery)

Anil K. Philip; Betty Philip

2010-01-01

309

Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies  

PubMed Central

In the United States, more than half of all new invasive cancers diagnosed are non-small cell lung cancer, with a significant number of these cases presenting at locally advanced stages, resulting in about one-third of all cancer deaths. While the advent of stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiotherapy, or SBRT) for early-staged patients has improved local tumor control to >90%, survival results for locally advanced stage lung cancer remain grim. Significant challenges exist in lung cancer radiation therapy including tumor motion, accurate dose calculation in low density media, limiting dose to nearby organs at risk, and changing anatomy over the treatment course. However, many recent technological advancements have been introduced that can meet these challenges, including four-dimensional computed tomography (4DCT) and volumetric cone-beam computed tomography (CBCT) to enable more accurate target definition and precise tumor localization during radiation, respectively. In addition, advances in dose calculation algorithms have allowed for more accurate dosimetry in heterogeneous media, and intensity modulated and arc delivery techniques can help spare organs at risk. New delivery approaches, such as tumor tracking and gating, offer additional potential for further reducing target margins. Image-guided adaptive radiation therapy (IGART) introduces the potential for individualized plan adaptation based on imaging feedback, including bulky residual disease, tumor progression, and physiological changes that occur during the treatment course. This review provides an overview of the current state of the art technology for lung cancer volume definition, treatment planning, localization, and treatment plan adaptation. PMID:24688775

Glide-Hurst, Carri K.

2014-01-01

310

700. Targeted delivery of a recombinant protein to neurons and astrocytes by transport and uptake via the low density lipoprotein (LDL) receptor for treatment of neurodegenerative disorders  

Microsoft Academic Search

Inherited lysosomal storage disorders occur in approximately 1 in 8000 births worldwide resulting from deficient activity of a key enzyme involved in catalysis of glucosaminoglycans resulting in symptoms ranging from skeletal deformities to progressive neuronal degeneration. Enzyme replacement therapy has been used to treat the peripheral symptoms; however, no treatment effectively treats the neurological disorders associated with the diseases. Gaucher's

Brian J. Spencer; Inder M. Verma

2004-01-01

311

Evaluation of antibacterial activity and cytocompatibility of ciprofloxacin loaded gelatin-hydroxyapatite scaffolds as a local drug delivery system for osteomyelitis treatment.  

PubMed

Surgical debridement of the dead bone and subsequent systemic antibiotic therapy is often ineffective in eliminating Staphylococcus aureus infections in osteomyelitic patients. The recurrence of S. aureus infection is mainly due to the intracellular growth of bacterial colonies within osteoblast cells that protect the organism from extracellular host defences and/or antibiotic therapy. In this study, porous gelatin-hydroxyapatite (HAP) scaffolds with various amounts of ciprofloxacin (1, 2, 5, and 10?wt%) were fabricated by freeze-drying technique and the release of the antibiotic was characterized, as was the efficacy of the released antibiotic against methicillin-sensitive and methicillin-resistant S. aureus. Furthermore, the impact of the released antibiotic on the viability and osteogenic differentiation of human adipose-derived mesenchymal stem cells (ADMSCs) cultured on the scaffolds were assessed. Finally, the efficacy of the released ciprofloxacin to enter the cells and abate intracellularly located S. aureus was evaluated. All the groups of CGHA scaffolds displayed sustained release of ciprofloxacin against S. aureus for 60 days above the minimum inhibitory concentration for the target species with zero-order kinetics and Korsmeyer-Peppas models. While comparing, the released antibiotic from CGHA5 scaffolds was found to be effective at reducing S. aureus through the study period, without detrimental effects on human ADMSC viability or osteogenic potential. When stem cells internalized with S. aureus were cultured onto the drug-loaded scaffolds, a significant reduction in the colony count of internalized bacteria was observed, resulting in the osteogenic differentiation capability of those cells. Our results clearly demonstrate that the ciprofloxacin incorporated gelatin-HAP scaffolds, which were cytocompatible and could target both intracellular and extracellular S. aureus, defining its potential to be used as local drug delivery system. PMID:25567452

Krishnan, Amit G; Jayaram, Lakshmi; Biswas, Raja; Nair, Manitha

2015-04-01

312

Whole-procedure clinical accuracy of Gamma Knife treatments of large lesions  

SciTech Connect

The mechanical accuracy of Gamma Knife radiosurgery based on single-isocenter measurement has been established to within 0.3 mm. However, the full delivery accuracy for Gamma Knife treatments of large lesions has only been estimated via the quadrature-sum analysis. In this study, the authors directly measured the whole-procedure accuracy for Gamma Knife treatments of large lesions to examine the validity of such estimation. The measurements were conducted on a head-phantom simulating the whole treatment procedure that included frame placement, computed tomography imaging, treatment planning, and treatment delivery. The results of the measurements were compared with the dose calculations from the treatment planning system. Average agreements of 0.1-1.6 mm for the isodose lines ranging from 25% to 90% of the maximum dose were found despite potentially large contributing uncertainties such as 3-mm imaging resolution, 2-mm dose grid size, 1-mm frame registration, multi-isocenter deliveries, etc. The results of our measurements were found to be significantly smaller (>50%) than the calculated value based on the quadrature-sum analysis. In conclusion, Gamma Knife treatments of large lesions can be delivered much more accurately than predicted from the quadrature-sum analysis of major sources of uncertainties from each step of the delivery chain.

Ma Lijun; Chuang, Cynthia; Descovich, Martina; Petti, Paula; Smith, Vernon; Verhey, Lynn [Department of Radiation Oncology, University of California San Francisco, San Francisco, California 94143 (United States)

2008-11-15

313

Impact of Intermittent Preventive Treatment in Pregnancy with Azithromycin-Containing Regimens on Maternal Nasopharyngeal Carriage and Antibiotic Sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus: a Cross-Sectional Survey at Delivery.  

PubMed

Sulfadoxine-pyrimethamine (SP) plus azithromycin (AZ) (SPAZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe pediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus at delivery among 854 women participating in a randomized controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest. Potential risk factors for carriage were examined. Nasopharyngeal carriage at delivery of S. pneumoniae (SPAZ, 7.2% [30/418], versus SPCQ, 19.3% [84/436]; P < 0.001) and H. influenzae (2.9% [12/418] versus 6.0% [26/436], P = 0.028), but not S. aureus, was significantly reduced among women who had received SPAZ-IPTp. The number of macrolide-resistant pneumococcal isolates was small but increased in the SPAZ group (13.3% [4/30], versus SPCQ, 2.2% [2/91]; P = 0.033). The proportions of isolates with serotypes covered by the 13-valent pneumococcal conjugate vaccine were similar (SPAZ, 10.3% [3/29], versus SPCQ, 17.6% [16/91]; P = 0.352). Although macrolide-resistant isolates were rare, they were more commonly detected in women who had received SPAZ-IPTp, despite the significant reduction of maternal carriage of S. pneumoniae and H. influenzae observed in this group. Future studies on SPAZ-IPTp should evaluate carriage and persistence of macrolide-resistant S. pneumoniae and other pathogenic bacteria in both mothers and infants and assess the clinical significance of their circulation. PMID:25673788

Unger, Holger W; Aho, Celestine; Ome-Kaius, Maria; Wangnapi, Regina A; Umbers, Alexandra J; Jack, Wanda; Lafana, Alice; Michael, Audrey; Hanieh, Sarah; Siba, Peter; Mueller, Ivo; Greenhill, Andrew R; Rogerson, Stephen J

2015-04-01

314

Delivery of behavioral HIV prevention services in New York City outpatient substance abuse treatment clinics: providers' perspectives on opportunities and challenges.  

PubMed

Providers (e.g., counselors, physicians) of substance abuse treatment have an opportunity to address HIV. This study identified: (1) providers' HIV prevention practices, (2) barriers, and (3) promoters to offering HIV prevention in substance abuse treatment. Semistructured qualitative interviews with one director, one medical provider, and four counselors, from each of six outpatient clinics (N = 36) were transcribed and coded according to thematic content analysis. Providers' practices included: (1) recommending condoms, (2) explaining HIV transmission, (3) HIV testing, and (4) assessing risk. Barriers included: (1) believing that clients know enough about HIV, (2) believing that clients are not at risk, (3) lacking information, (4) outdated training (i.e., > 5 years ago), (5) HIV stigma, and (6) avoidance. While some providers recommended condoms and HIV testing, many avoided discussing HIV. Our results suggest a need for training to improve understanding of HIV transmission, effective counseling practices, and to build capacity for HIV testing or linkages with HIV service agencies. PMID:25646726

Spector, Anya Y; Remien, Robert H

2015-02-01

315

Intracarotid Delivery of Drugs: The Potential and the Pitfalls  

PubMed Central

The major efforts to selectively deliver drugs to the brain in the last decade have relied on smart molecular techniques to penetrate the blood brain barrier while intraarterial drug delivery has drawn relatively little attention. In the last decade there have been rapid advances in endovascular techniques. Modern endovascular procedures can permit highly targeted drug delivery by intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart-neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggests that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs. PMID:18719453

Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

2014-01-01

316

Power Delivery of the Future  

E-print Network

This paper is written to provide an insight into the physics and engineering that go into power delivery of the future. Topics covered are Fault Current Limiters (FCL) including Superconducting FCL and Emission Limited FCL; Lightning and Restoration Preparedness; Compressed-Gas-Insulated Delivery; Evaporative Cooling Delivery; Advanced Delivery Technologies Requiring Big Breakthroughs such as Conducting Polymers, Electron-Beam Delivery, Microwave Delivery, and Laser-Beam Delivery.

Mario Rabinowitz

2003-04-26

317

IMRT treatment Monitor Unit verification using absolute calibrated BEAMnrc and Geant4 Monte Carlo simulations  

NASA Astrophysics Data System (ADS)

Intensity Modulated Radiation Therapy (IMRT) treatments are some of the most complex being delivered by modern megavoltage radiotherapy accelerators. Therefore verification of the dose, or the presecribed Monitor Units (MU), predicted by the planning system is a key element to ensuring that patients should receive an accurate radiation dose plan during IMRT. One inherently accurate method is by comparison with absolute calibrated Monte Carlo simulations of the IMRT delivery by the linac head and corresponding delivery of the plan to a patient based phantom. In this work this approach has been taken using BEAMnrc for simulation of the treatment head, and both DOSXYZnrc and Geant4 for the phantom dose calculation. The two Monte Carlo codes agreed to within 1% of each other, and these matched very well to our planning system for IMRT plans to the brain, nasopharynx, and head and neck.

Oborn, B. M.; Williams, M.; Bailey, M.; Carolan, M. G.

2014-03-01

318

Development of a Microfluidics-Based Intracochlear Drug Delivery Device  

Microsoft Academic Search

Background: Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods: We have taken a microfluidics\\/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the

William F. Sewell; Jeffrey T. Borenstein; Zhiqiang Chen; Jason Fiering; Ophir Handzel; Maria Holmboe; Ernest S. Kim; Sharon G. Kujawa; Michael J. McKenna; Mark M. Mescher; Brian Murphy; Erin E. Leary Swan; Marcello Peppi; Sarah Tao

2009-01-01

319

Co-delivery of HIF1? siRNA and gemcitabine via biocompatible lipid-polymer hybrid nanoparticles for effective treatment of pancreatic cancer.  

PubMed

Hypoxia-inducible factor 1? (HIF1?) has emerged as a promising new target for pancreatic cancer treatment over the past decade. High expression of HIF-1? increases the drug resistance of the current first line chemotherapeutic drug, gemcitabine (Gem). Here we employed biocompatible lipid-polymer hybrid nanoparticles to co-deliver HIF1? siRNA (si-HIF1?) and Gem for pancreatic cancer treatment in subcutaneous and orthotopic tumor models. The cationic ?-polylysine co-polymer (ENPs) can effectively absorb negatively charged si-HIF1? on the surface and encapsulate Gem to the hydrophilic core. Further coating of ENPs with PEGylated lipid bilayer resulted formation of LENPs, with reversed surface charge. The lipid bilayer of LENPs prevented nanoparticle aggregation and si-HIF1? degradation in serum, as well as Gem leakage. Those characteristics endow LENPs encapsulating drug prolonged lifetime in bloodstream and improved drug release via the enhanced tumor vasculature effect in tumor tissues. LENPs can co-deliver Gem and si-HIF1? (LENP-Gem-si-HIF1?) into tumor cells and effectively suppress the HIF1? expression both in vitro and in vivo. LENP-Gem-siHIF1? exhibited significant synergistic antitumor effects. Furthermore, LENP-Gem-si-HIF1? showed excellent capability to inhibit tumor metastasis in orthotopic tumor model. PMID:25678112

Zhao, Xiao; Li, Feng; Li, Yiye; Wang, Hai; Ren, He; Chen, Jing; Nie, Guangjun; Hao, Jihui

2015-04-01

320

Adeno-associated Virus–mediated Delivery of a Recombinant Single-chain Antibody Against Misfolded Superoxide Dismutase for Treatment of Amyotrophic Lateral Sclerosis  

PubMed Central

There is emerging evidence that the misfolding of superoxide dismutase 1 (SOD1) may represent a common pathogenic event in both familial and sporadic amyotrophic lateral sclerosis (ALS). To reduce the burden of misfolded SOD1 species in the nervous system, we have tested a novel therapeutic approach based on adeno-associated virus (AAV)–mediated tonic expression of a DNA construct encoding a secretable single-chain fragment variable (scFv) antibody composed of the variable heavy and light chain regions of a monoclonal antibody (D3H5) binding specifically to misfolded SOD1. A single intrathecal injection of the AAV encoding the single-chain antibody in SOD1G93A mice at 45 days of age resulted in sustained expression of single-chain antibodies in the spinal cord, and it delayed disease onset and extension of life span by up to 28%, in direct correlation with scFv titers in the spinal cord. The treatment caused attenuation of neuronal stress signals and reduction in levels of misfolded SOD1 in the spinal cord of SOD1G93A mice. From these results, we propose that an immunotherapy based on intrathecal inoculation of AAV encoding a secretable scFv against misfolded SOD1 should be considered as potential treatment for ALS, especially for individuals carrying SOD1 mutations. PMID:24394188

Patel, Priyanka; Kriz, Jasna; Gravel, Mathieu; Soucy, Geneviève; Bareil, Christine; Gravel, Claude; Julien, Jean-Pierre

2014-01-01

321

Clinical effect of continuous corrective force delivery in the non-operative treatment of idiopathic scoliosis: a prospective cohort study of the triac-brace  

PubMed Central

A prospective cohort study of skeletally immature idiopathic scoliotic patients treated with the TriaC brace. To determine if the TriaC brace is effective in preventing curve progression in immature adolescent idiopathic scoliotic patients with a very high risk of curve progression based on reported natural history data. The aim of the newly introduced TriaC brace is to reverse the pathologic transverse force pattern by externally applied and continuously present orthotic forces. In the frontal plane the force system used in the TriaC brace is similar to the force system of the conventional braces. However, in the sagittal plane the force system acts only on the thoracic region. In addition, the brace allows upper trunk flexibility without affecting the corrective forces during body motion. In a preliminary study it is demonstrated that the brace prevents further progression of both the Cobb angle and axial rotation in idiopathic scoliosis. Skeletally immature patients with idiopathic scoliosis with curves between 20 and 40° were studied prospectively. Skeletally immature was defined as a Risser sign 0 or 1 for both boys and girls, or pre-menarche or less than 1-year post-menarche for girls. Curves of less than 30° had to have documented progression before entry. The mean age of the patients at the start of treatment was 11.3 ± 3.1 years. All measurements were collected by a single observer, and all patients were followed up to skeletal maturity. Treatment was complete for all participants when they had reached Risser sign 4 and did not show any further growth at length measurements. This was at a mean age of 15.6 ± 1.1 years, with a mean follow-up of 1.6 years post bracing. In our study a successful outcome was obtained in 76% of patients treated with the TriaC brace. Comparing our data to literature data on natural history of a similar cohort shows that the TriaC brace significantly alters the predicted natural history. The current study demonstrates that treatment with the TriaC brace reduces the scoliosis, and that the achieved correction is maintained in some degree after skeletal maturity is reached and bracing is discontinued. It also prevents further progression of the Cobb angle in idiopathic scoliosis. The new brace does not differ from the conventional braces as far as maintaining the deformity is concerned. PMID:17926071

Veldhuizen, Albert G.; Nijenbanning, Gert

2007-01-01

322

Clinical effect of continuous corrective force delivery in the non-operative treatment of idiopathic scoliosis: a prospective cohort study of the TriaC-brace.  

PubMed

A prospective cohort study of skeletally immature idiopathic scoliotic patients treated with the TriaC brace. To determine if the TriaC brace is effective in preventing curve progression in immature adolescent idiopathic scoliotic patients with a very high risk of curve progression based on reported natural history data. The aim of the newly introduced TriaC brace is to reverse the pathologic transverse force pattern by externally applied and continuously present orthotic forces. In the frontal plane the force system used in the TriaC brace is similar to the force system of the conventional braces. However, in the sagittal plane the force system acts only on the thoracic region. In addition, the brace allows upper trunk flexibility without affecting the corrective forces during body motion. In a preliminary study it is demonstrated that the brace prevents further progression of both the Cobb angle and axial rotation in idiopathic scoliosis. Skeletally immature patients with idiopathic scoliosis with curves between 20 and 40 degrees were studied prospectively. Skeletally immature was defined as a Risser sign 0 or 1 for both boys and girls, or pre-menarche or less than 1-year post-menarche for girls. Curves of less than 30 degrees had to have documented progression before entry. The mean age of the patients at the start of treatment was 11.3 +/- 3.1 years. All measurements were collected by a single observer, and all patients were followed up to skeletal maturity. Treatment was complete for all participants when they had reached Risser sign 4 and did not show any further growth at length measurements. This was at a mean age of 15.6 +/- 1.1 years, with a mean follow-up of 1.6 years post bracing. In our study a successful outcome was obtained in 76% of patients treated with the TriaC brace. Comparing our data to literature data on natural history of a similar cohort shows that the TriaC brace significantly alters the predicted natural history. The current study demonstrates that treatment with the TriaC brace reduces the scoliosis, and that the achieved correction is maintained in some degree after skeletal maturity is reached and bracing is discontinued. It also prevents further progression of the Cobb angle in idiopathic scoliosis. The new brace does not differ from the conventional braces as far as maintaining the deformity is concerned. PMID:17926071

Bulthuis, Gerben J; Veldhuizen, Albert G; Nijenbanning, Gert

2008-02-01

323

Oxygen delivery to and use by primary porcine hepatocytes in the HepatAssist 2000 system for extracorporeal treatment of patients in end-stage liver failure.  

PubMed

A system for the extracorporeal treatment of end-stage liver failure patients has been developed and is now in clinical studies. This HepatAssist 2000 system consists of perfusing the plasma of the patient through a hollow-fiber bioreactor containing primary porcine hepatocytes. The goal of the system is to assist the patient while the liver regenerates or a suitable liver is found for transplantation. During the development of this system in the laboratory, an experimental protocol has been developed to simulate patient treatments. The protocol substitutes donor calf serum for patient plasma, but is otherwise similar to clinical conditions. The protocol uses a blood gas analyzer to monitor dissolved oxygen and carbon dioxide tensions at the entrance to and exit from the bioreactor. Samples are withdrawn using a standard 1-ml syringe and analyzed off-line immediately. The blood gas measurements have been used to verify that the oxygenator, placed immediately prior to the bioreactor in the plasma circuit, is properly sized to allow complete equilibration with feed gas and to maintain a physiologic level of carbon dioxide. The measurements were also used to calculate overall bioreactor oxygen consumption rates under various conditions. In one set of studies, composition of the feed gas to the oxygenator was varied from 20% to 70% oxygen, while maintaining 5% carbon dioxide and balance nitrogen. Rates of oxygen consumption and liver cell function (metabolism of diazepam) were unchanged, and no signs of oxygen toxicity were observed. In another set of studies, oxygen consumption increased linearly with number of hepatocytes used in the clinically used range of 5-10 billion hepatocytes, whether all hepatocytes were placed in one device or split between two devices operating in series or in parallel. In a third set of studies, oxygen consumption was a weak function of flowrate through the bioreactor but was highest at the clinically used recirculation rate of 400 ml/min. These data indicate that blood gas meters--readily available in hospital clinical laboratories--can be used to assist in the design of extracorporeal cell therapies, to monitor the effectiveness of system components, and to assess the effects of system modifications. These same measurements can be made noninvasively in the clinical setting to monitor oxygen consumption rates during patient treatment. PMID:9889900

Custer, L; Mullon, C J

1998-01-01

324

Finding the striatum in sheep: use of a multi-modal guided approach for convection enhanced delivery.  

PubMed

Our goal is delivery of a long-term treatment for Huntington's disease. We administer intracerebrally in sheep adeno-associated virus (AAV) to establish optimal safety, spread and neuronal uptake of AAV based therapeutics. Sheep have large gyrencephalic brains and offer the opportunity to study a transgenic Huntington's disease model. However, lack of a relevant brain stereotactic atlas and the difficulty of skull fixation make conventional stereotaxy unreliable. We describe a multi-modal image-guidance technique to achieve accurate placement of therapeutics into the sheep striatum. PMID:25063428

van der Bom, I M J; Moser, R P; Gao, G; Mondo, E; O'Connell, D; Gounis, M J; McGowan, S; Chaurette, J; Bishop, N; Sena-Esteves, M S; Mueller, C; Aronin, N

2013-01-01

325

Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues  

PubMed Central

Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair. PMID:22433782

Nichols, Scott P.; Storm, Wesley L.; Koh, Ahyeon; Schoenfisch, Mark H.

2012-01-01

326

Delivery system for molten salt oxidation of solid waste  

DOEpatents

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

Brummond, William A. (Livermore, CA); Squire, Dwight V. (Livermore, CA); Robinson, Jeffrey A. (Manteca, CA); House, Palmer A. (Walnut Creek, CA)

2002-01-01

327

Local delivery of hyaluronan 0.8% as an adjunct to scaling and root planing in the treatment of chronic periodontitis: A clinical and microbiological study  

PubMed Central

Background: The purpose of this study was to assess the clinical and microbiological effects of the local and sub-gingival application of a hyaluronan gel on scaling and root planing (SRP) in the treatment of moderate generalized chronic periodontitis. Materials and Methods: In this split mouth study, 72 teeth in 18 patients with generalized chronic periodontitis with moderate severity were chosen for the study. Plaque samples were obtained by paper points at required intervals. Contra-lateral pairs of premolars and canine teeth in the maxilla or the mandible were selected to receive test treatment or serve as controls. Experimental jaw quadrants received sub-gingival administration of 0.2-ml 0.8% hyaluronan gel into selected sites following SRP and 1-week later. Clinical parameters were assessed at baseline, 1st, 4th, and 12th week. Colony-forming units (CFU) per milliliter were assessed at baseline, after SRP and after 2 weeks of drug insertion Student t-test and repeated measure ANOVA (RMANOVA) were used in this study. RMANOVA was used to find the significance in bleeding on probing (BOP) and plaque index (PI) and t-test for probing pocket depth (PPD) and clinical attachment level (CAL). Results: The results revealed that there was a significant reduction in BOP (P < 0.001) PI (P < 0.001), PPD (P < 0.001) and CAL (P < 0.001) were also observed in experimental jaw quadrant following SRP and insertion of 0.8% hyaluronan when compared with the control group. A statistically significant reduction of CFUs was also found (P < 0.001) in the experimental site when compared with the control site. Conclusion: Sub-gingival placement of 0.2-ml of 0.8% hyaluronan along with SRP resulted in a significant improvement in both clinical and microbiological parameters when compared with the control site. PMID:25810591

Polepalle, Tejaswin; Srinivas, Moogala; Swamy, Narasimha; Aluru, Sudheer; Chakrapani, Swarna; Chowdary, Bollepalli Appaiah

2015-01-01

328

Increasing the Efficiency of Parkinson's Disease Treatment Using a poly(lactic-co-glycolic acid) (PLGA) Based L-DOPA Delivery System  

PubMed Central

To compare the efficacy of L-DOPA administered intranasally in the form of nanoparticles (nano-DOPA) and in standard drug forms using a rat Parkinson's Disease (PD) model. L-DOPA-containing nanoparticles (250±50 nm) were synthesized using the double emulsion method. The efficacy of nano-DOPA therapy was studied in Wistar rats with 6-OHDA-induced PD. Drugs were administered daily, 0.35 mg/kg (by L-DOPA). Animals' motor coordination and behavior were analyzed using the forelimb placing task and several other tests. Thirty minutes after the first administration, animals treated with L-DOPA, L-DOPA+benserazide, and nano-DOPA showed equally significant (p<0.05) improvements in coordination performance in comparison to the non-treated group. After 4 weeks of treatment, coordination performance in the nano-DOPA group (89±13% of the intact control level) was twice as high as in the L-DOPA and L-DOPA+benserazide groups, which did not differ from non-treated animals. The effect of nano-DOPA was significantly higher and more long-lasting (90±13% at 24 h after administration); moreover, it was still significant one week after the treatment was discontinued. Intranasal nano-DOPA was found to provide a lasting motor function recovery in the 6-OHDA-induced rat PD model with the effect sustained for one week after discontinuation, while the same doses of standard drugs provided significant effect only after the first administration. L-DOPA administered in the form of PLGA-based nanoparticles had a higher effective half-life, bioavailability, and efficacy; it was also efficiently delivered to the brain by intranasal administration. PMID:25258572

Kondrasheva, I.G.; Severin, E.S.; Guseva, A.A.; Kamensky, A.A.

2014-01-01

329

Non-invasive, photonics-based diagnostic, imaging, monitoring, and light delivery techniques for the recognition, quantification and treatment of malignant and chronic inflammatory conditions  

NASA Astrophysics Data System (ADS)

We report firsthand on innovative developments in non-invasive, biophotonic techniques for a wide range of diagnostic, imaging and treatment options, including the recognition and quantification of cancerous, pre-cancerous cells and chronic inflammatory conditions. These techniques have benefited from the ability to target the affected site by both monochromatic light and broad multiple wavelength spectra. The employment of such wavelength or color-specific properties embraces the fluorescence stimulation of various photosensitizing drugs, and the instigation and detection of identified fluorescence signatures attendant upon laser induced fluorescence (LIF) phenomena as transmitted and propagated by precancerous, cancerous and normal tissue. In terms of tumor imaging and therapeutic and treatment options, we have exploited the abilities of various wavelengths to penetrate to different depths, through different types of tissues, and have explored quantifiable absorption and reflection characteristics upon which diagnostic assumptions can be reliably based and formulated. These biophotonic-based diagnostic, sensing and imaging techniques have also benefited from, and have been further enhanced by, the integrated ability to provide various power levels to be employed at various stages in the procedure. Applications are myriad, including non-invasive, non destructive diagnosis of in vivo cell characteristics and functions; light-based tissue analysis; real-time monitoring and mapping of brain function and of tumor growth; real time monitoring of the surgical completeness of tumor removal during laser-imaged/guided brain resection; diagnostic procedures based on fluorescence life-time monitoring, the monitoring of chronic inflammatory conditions (including rheumatoid arthritis), and continuous blood glucose monitoring in the control of diabetes.

Davies, N.; Davies-Shaw, D.; Shaw, J. D.

2007-02-01

330

Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin.  

PubMed

The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA-MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA-MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA-MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA-MWCNTs in a similar manner. Our results clearly show that HSA-MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating. PMID:21289990

Iancu, Cornel; Mocan, Lucian; Bele, Constantin; Orza, Anamaria Ioana; Tabaran, Flaviu A; Catoi, Cornel; Stiufiuc, Rares; Stir, Ariana; Matea, Cristian; Iancu, Dana; Agoston-Coldea, Lucia; Zaharie, Florin; Mocan, Teodora

2011-01-01

331

Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin  

PubMed Central

The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA–MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA–MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA–MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA–MWCNTs in a similar manner. Our results clearly show that HSA–MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating. PMID:21289990

Iancu, Cornel; Mocan, Lucian; Bele, Constantin; Orza, Anamaria Ioana; Tabaran, Flaviu A; Catoi, Cornel; Stiufiuc, Rares; Stir, Ariana; Matea, Cristian; Iancu, Dana; Agoston-Coldea, Lucia; Zaharie, Florin; Mocan, Teodora

2011-01-01

332

Materials innovation for co-delivery of diverse therapeutic cargos  

PubMed Central

Co-delivery is a rapidly growing sector of drug delivery that aspires to enhance therapeutic efficacy through controlled delivery of diverse therapeutic cargoes with synergistic activities. It requires the design of carriers capable of simultaneously transporting to and releasing multiple therapeutics at a disease site. Co-delivery has arisen from the emerging trend of combination therapy, where treatment with two or more therapeutics at the same time can succeed where single therapeutics fail. However, conventional combination therapy offers little control over achieving an optimized therapeutic ratio at the target site. Co-delivery via inclusion of multiple therapeutic cargos within the same carrier addresses this issue by not only ensuring delivery of both therapeutics to the same cell, but also offering a platform for control of the delivery process, from loading to release. Co-delivery systems have been formulated using a number of carriers previously developed for single-therapeutic delivery. Liposomes, polymeric micelles, PLGA nanoparticles, and dendrimers have all been adapted for co-delivery. Much of the effort focuses on dealing with drugs having dissimilar properties, increasing loading efficiencies, and controlling loading and release ratios. In this review, we highlight the innovations in carrier designs and formulations to deliver combination cargoes of drug/drug, drug/siRNA, and drug/pDNA toward disease therapy. With rapid advances in mechanistic understanding of interrelating molecular pathways and development of molecular medicine, the future of co-delivery will become increasingly promising and prominent. PMID:24818000

Godsey, Megan E; Suryaprakash, Smruthi; Leong, Kam W

2014-01-01

333

Importance of novel drug delivery systems in herbal medicines  

PubMed Central

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

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

2010-01-01

334

Convection-enhanced delivery to the central nervous system.  

PubMed

Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS. PMID:25397365

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

2015-03-01

335

Nano and Microparticles as Controlled Drug Delivery Devices  

Microsoft Academic Search

Although, the drug delivery system (DDS) concept is not new, great progress has recently been made in the treatment of a variety of diseases. Targeting delivery of drugs to the diseased lesions is one of the most important aspects of DDS. To convey a sufficient dose of drug to the lesion, suitable carriers of drugs are needed. Nano and microparticle

Majeti N. V. Ravi

2000-01-01

336

Application of Sterylglucoside-Containing Particles for Drug Delivery  

Microsoft Academic Search

Recent advances in biotechnology have promoted biomolecular targeting of drugs, peptides and genes in the treatment and management of major diseases and infections. Therapeutic development of drugs and delivery systems may have various objectives: Systemic drugs require optimal delivery and uptake at target sites; peptide drugs require alternative routes of administration, such as nasal or intestinal absorption; gene medicines need

Yoshie Maitani; Koji Nakamura; Kumi Kawano

337

Current status and future potential of transdermal drug delivery  

Microsoft Academic Search

The past twenty five years have seen an explosion in the creation and discovery of new medicinal agents. Related innovations in drug delivery systems have not only enabled the successful implementation of many of these novel pharmaceuticals, but have also permitted the development of new medical treatments with existing drugs. The creation of transdermal delivery systems has been one of

Mark R. Prausnitz; Samir Mitragotri; Robert Langer

2004-01-01

338

Biodegradable hybrid polymeric membranes for ocular drug delivery  

Microsoft Academic Search

Ophthalmic delivery systems such as ocular inserts are useful strategies to improve the ocular bioavailability of topically administered drugs. In the present study polyvinyl alcohol and sodium carboxymethylcellulose based ocular inserts were prepared by solution casting for sustained drug delivery of ciprofloxacin for treatment of topical infections. The polymers were esterified and the formation of ester bonds was confirmed by

Dharmendra Jain; Edmund Carvalho; R. Banerjee

2010-01-01

339

Delivery of Aerosolized Liposomal Amikacin as a Novel Approach for the Treatment of Nontuberculous Mycobacteria in an Experimental Model of Pulmonary Infection  

PubMed Central

Pulmonary infections caused by nontuberculous mycobacteria (NTM) are an increasing problem in individuals with chronic lung conditions and current therapies are lacking. We investigated the activity of liposomal amikacin for inhalation (LAI) against NTM in vitro as well as in a murine model of respiratory infection. Macrophage monolayers were infected with three strains of Mycobacterium avium, two strains of Mycobacterium abscessus, and exposed to LAI or free amikacin for 4 days before enumerating bacterial survival. Respiratory infection was established in mice by intranasal inoculation with M. avium and allowing three weeks for the infection to progress. Three different regimens of inhaled LAI were compared to inhaled saline and parenterally administered free amikacin over a 28 day period. Bacteria recovered from the mice were analyzed for acquired resistance to amikacin. In vitro, liposomal amikacin for inhalation was more effective than free amikacin in eliminating both intracellular M. avium and M. abscessus. In vivo, inhaled LAI demonstrated similar effectiveness to a ?25% higher total dose of parenterally administered amikacin at reducing M. avium in the lungs when compared to inhaled saline. Additionally, there was no acquired resistance to amikacin observed after the treatment regimen. The data suggest that LAI has the potential to be an effective therapy against NTM respiratory infections in humans. PMID:25264757

Rose, Sasha J.; Neville, Mary E.; Gupta, Renu; Bermudez, Luiz E.

2014-01-01

340

Brain drug delivery systems for neurodegenerative disorders.  

PubMed

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

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

2012-09-01

341

Barriers to drug delivery in solid tumors  

PubMed Central

Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

2014-01-01

342

FUEL DELIVERY TEMPERATURE STUDY  

E-print Network

Elkins ­ California State Water Resources Control Board Kurt Floren ­ Los Angeles County AgriculturalCALIFORNIA ENERGY COMMISSION FUEL DELIVERY TEMPERATURE STUDY COMMISSIONREPORT March 2009 CEC-600 and Nicholas Janusch, 2009. Fuel Delivery Temperature Study, California Energy Commission. CEC-600-2009-002-CMF

343

Total Body Irradiation, Toward Optimal Individual Delivery: Dose Evaluation With Metal Oxide Field Effect Transistors, Thermoluminescence Detectors, and a Treatment Planning System  

SciTech Connect

Purpose: To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. Methods and Materials: A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. Results: The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. Conclusions: The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

Bloemen-van Gurp, Esther J. [Department of Radiation Oncology, Maastro Clinic, GROW, University Hospital Maastricht, Maastricht (Netherlands)], E-mail: esther.bloemen@maastro.nl; Mijnheer, Ben J.; Verschueren, Tom A.M.; Lambin, Philippe [Department of Radiation Oncology, Maastro Clinic, GROW, University Hospital Maastricht, Maastricht (Netherlands)

2007-11-15

344

Bioavailability of phytochemicals and its enhancement by drug delivery systems  

PubMed Central

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

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

2013-01-01

345

Time-Accurate Computational Simulation  

NASA Technical Reports Server (NTRS)

Time accurate CFD may offer a faster approach to S&C aerodynamic database population than the conventional point by point steady state CFD. We would directly simulate -, -sweeps or other configuration movements typically of measurement sequence in wind tunnels. A second objective is to demonstrate potential applications to assessment of S&C dynamic derivatives by simulating vehicle motions such as free to roll, and nonlinearity such as the trends of aerodynamic forces near CL-max or flow hysteresis.

Pao, S. Paul; Buning, Pieter G.

2004-01-01

346

Novel drug delivery systems for glaucoma  

PubMed Central

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

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

2011-01-01

347

Delivery efficiency of an Elekta linac under gated operation.  

PubMed

In this study, we have characterized the efficiency of an Elekta linac in the delivery of gated radiotherapy. We have explored techniques to reduce the beam-on delay and to improve the delivery efficiency, and have investigated the impact of frequent beam interruptions on the dosimetric accuracy of gated deliveries. A newly available gating interface was installed on an Elekta Synergy. Gating signals were generated using a surface mapping system in conjunction with a respiratory motion phantom. A series of gated deliveries were performed using volumetric modulated arc therapy (VMAT) treatment plans previously generated for lung cancer patients treated with stereotactic body radiotherapy. Baseline values were determined for the delivery times. The machine was then tuned in an effort to minimize beam-on delays and improve delivery efficiency. After that process was completed, the dosimetric accuracy of the gated deliveries was evaluated by comparing the measured and the planned coronal dose distributions using gamma index analyses. Comparison of the gated and the non-gated deliveries were also performed. The results demonstrated that, with the optimal machine settings, the average beam-on delay was reduced to less than 0.22 s. High dosimetric accuracy was demonstrated with gamma index passing rates no lower than 99.0% for all tests (3%/3 mm criteria). Consequently, Elekta linacs can provide a practical solution for gated VMAT treatments with high dosimetric accuracy and only a moderate increase in the overall delivery time. PMID:25207561

Cui, Guoqiang; Housley, David J; Chen, Fan; Mehta, Vivek K; Shepard, David M

2014-01-01

348

Delivery quality assurance with ArcCHECK  

SciTech Connect

Radiation therapy requires delivery quality assurance (DQA) to ensure that treatment is accurate and closely follows the plan. We report our experience with the ArcCHECK phantom and investigate its potential optimization for the DQA process. One-hundred seventy DQA plans from 84 patients were studied. Plans were classified into 2 groups: those with the target situated on the diodes of the ArcCHECK (D plans) and those with the target situated at the center (C plans). Gamma pass rates for 8 target sites were examined. The parameters used to analyze the data included 3%/3 mm with the Van Dyk percent difference criteria (VD) on, 3%/3 mm with the VD off, 2%/2 mm with the VD on, and x/3 mm with the VD on and the percentage dosimetric agreement “x” for diode plans adjusted. D plans typically displayed maximum planned dose (MPD) on the cylindrical surface containing ArcCHECK diodes than center plans, resulting in inflated gamma pass rates. When this was taken into account by adjusting the percentage dosimetric agreement, C plans outperformed D plans by an average of 3.5%. ArcCHECK can streamline the DQA process, consuming less time and resources than radiographic films. It is unnecessary to generate 2 DQA plans for each patient; a single center plan will suffice. Six of 8 target sites consistently displayed pass rates well within our acceptance criteria; the lesser performance of head and neck and spinal sites can be attributed to marginally lower doses and increased high gradient of plans.

Neilson, Christopher; Klein, Michael; Barnett, Rob [London Regional Cancer Program, London Health Sciences Centre, London, Ontario (Canada); Yartsev, Slav, E-mail: slav.yartsev@lhsc.on.ca [London Regional Cancer Program, London Health Sciences Centre, London, Ontario (Canada)

2013-04-01

349

Coaxial electrohydrodynamic atomization: Microparticles for drug delivery applications.  

PubMed

As cancer takes its toll on human health and well-being, standard treatment techniques such as chemotherapy and radiotherapy often fall short of ideal solutions. In particular, adverse side effects due to excess dosage and collateral damage to healthy cells as well as poor patient compliance due to multiple administrations continue to pose challenges in cancer treatment. Thus, the development of appropriately engineered drug delivery systems (DDS) for effective, controlled and sustained delivery of drugs is of interest for patient treatment. Moreover, the physiopathological characteristics of tumors play an essential role in the success of cancer treatment. Here, we present an overview of the application of double-walled microparticles for local drug delivery with particular focus on the electrohydrodynamic atomization (EHDA) technique and its fabrication challenges. The review highlights the importance of a combination of experimental data and computational simulations for the design of an optimal delivery system. PMID:25483422

Davoodi, Pooya; Feng, Fang; Xu, Qingxing; Yan, Wei-Cheng; Tong, Yen Wah; Srinivasan, M P; Sharma, Vijay Kumar; Wang, Chi-Hwa

2015-05-10

350

A fully implantable intracochlear drug delivery device : development and characterization  

E-print Network

In a collaborative effort with the Massachusetts Eye and Ear Infirmary, Draper Laboratory is developing an implantable microfluidic drug delivery system for long-term treatment of inner ear disorders and prevention of ...

Swan, Erin Eileen Leary, 1976-

2009-01-01

351

Nanoparticle-based drug delivery to the vagina: a review.  

PubMed

Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

Ensign, Laura M; Cone, Richard; Hanes, Justin

2014-09-28

352

Psychosocial, behavioural and health system barriers to delivery and uptake of intermittent preventive treatment of malaria in pregnancy in Tanzania – viewpoints of service providers in Mkuranga and Mufindi districts  

PubMed Central

Background Intermittent preventive treatment of malaria in pregnancy (IPTp) using sulphurdoxine-pyrimethamine (SP) is one of key malaria control strategies in Africa. Yet, IPTp coverage rates across Africa are still low due to several demand and supply constraints. Many countries implement the IPTp-SP strategy at antenatal care (ANC) clinics. This paper reports from a study on the knowledge and experience of health workers (HWs) at ANC clinics regarding psychosocial, behavioural and health system barriers to IPTp-SP delivery and uptake in Tanzania. Methods Data were collected through questionnaire-based interviews with 78 HWs at 28 ANC clinics supplemented with informal discussions with current and recent ANC users in Mkuranga and Mufindi districts. Qualitative data were analysed using a qualitative content analysis approach. Quantitative data derived from interviews with HWs were analysed using non-parametric statistical analysis. Results The majority of interviewed HWs were aware of the IPTp-SP strategy’s existence and of the recommended one month spacing of administration of SP doses. Some HWs were unsure of that it is not recommended to administer IPTp-SP and ferrous/folic acid concurrently. Others were administering three doses of SP per client following instruction from a non-governmental agency while believing that this was in conflict with national guidelines. About half of HWs did not find it appropriate for the government to recommend private ANC providers to provide IPTp-SP free of charge since doing so forces private providers to recover the costs elsewhere. HWs noted that pregnant women often register at clinics late and some do not comply with the regularity of appointments for revisits, hence miss IPTp and other ANC services. HWs also noted some amplified rumours among clients regarding health risks and treatment failures of SP used during pregnancy, and together with clients’ disappointment with waiting times and the sharing of cups at ANC clinics for SP, limit the uptake of IPTp-doses. Conclusion HWs still question SP’s treatment advantages and are confused about policy ambiguity on the recommended number of IPTp-SP doses and other IPTp-SP related guidelines. IPTp-SP uptake is further constrained by pregnant women’s perceived health risks of taking SP and of poor service quality. PMID:24410770

2014-01-01

353

Physical blends of starch graft copolymers as matrices for colon targeting drug delivery systems  

Microsoft Academic Search

Colon targeting drug delivery systems have attracted many researchers due to the distinct advantages they present such as near neutral pH, longer transit time and reduced enzymatic activity. Moreover, in recent studies, colon specific drug delivery systems are gaining importance for use in the treatment of local pathologies of the colon and also for the systemic delivery of protein and

I. Silva; M. Gurruchaga; I. Goñi

2009-01-01

354

MODIFICATION AND CHARACTERIZATION OF DRY MATERIAL FEEDER FOR DELIVERY OF RED AND VIOLET DYE MIXTURES  

EPA Science Inventory

Uniform delivery of dry material for stable concentrations of aerosols in inhalation exposure chambers is essential in inhalation experiments. his paper characterizes an AccuRate dry material feeder with modifications, for different helix sizes, actuation rates, nozzle types and ...

355

Design and in vitro development of resorbable urologic drug delivery device  

E-print Network

Implantable, controlled release drug delivery devices offer several advantages over systemic oral administration routes and immediate drug release treatments including direct therapy to target organ, more continuous ...

Tobias, Irene S. (Irene Sophie)

2008-01-01

356

Vaginal delivery in patients with a prior cesarean section.  

PubMed

To assess the risks and benefits of vaginal delivery in patients with prior cesarean section, the English literature on this subject from 1950 to 1980 was reviewed. The following conclusions were reached: 1) Properly conducted vaginal delivery after cesarean section is relatively safe, with a 0.7% incidence of uterine rupture, 0.93 perinatal mortality, and no maternal deaths due to uterine rupture. 2) Of those patients allowed a trial of labor, 66.7% were successfully delivered vaginally. Successful vaginal delivery occurred in 74.2% of those patients with a nonrecurrent indication for their previous cesarean section and in 33.3% of those patients whose indication for previous cesarean section was cephalopelvic disproportion. Sixty-seven percent of those patients with a prior vaginal delivery versus 47.1% of those patients without a prior vaginal delivery subsequently delivered vaginally. 3) A classic uterine scar clearly increases the probability of uterine rupture. However, the precise magnitude of the increased risk cannot be accurately determined. 4) Certain basic safety requirements such as available operating room facilities and adequate personnel for careful observation are mandatory, but other management policies that remain controversial include use of regional anesthesia, oxytocin administration, timing of hospital admission, artificial rupture of membranes, mode of delivery, proper method to evaluate the uterine scar, and delivery of fetuses in breech presentation and twins. 5) A policy of selective vaginal deliveries among patients with prior cesarean sections will result in cost reductions due to decreased postpartum hospitalization. PMID:7078857

Lavin, J P; Stephens, R J; Miodovnik, M; Barden, T P

1982-02-01

357

Synthetic tumor networks for screening drug delivery systems.  

PubMed

Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle's physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of "leaky vessels". Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening. PMID:25599856

Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B; Garson, Charles J; Mills, Ivy R; Matar, Majed M; Fewell, Jason G; Pant, Kapil

2015-03-10

358

Accurate vacuum-polarization calculations  

NASA Astrophysics Data System (ADS)

A numerical scheme for evaluating the part of the one-photon vacuum-polarization effect not accounted for by the Uehling potential (the Wichmann-Kroll effect) is presented. The method can be used with an arbitary atomic model potential describing the bound electrons. Benchmark results for this effect are presented for hydrogenlike levels using a uniform nuclear-charge distribution. The effect of direct and exchange electron screening on the vacuum polarization are discussed in connection with the accurately measured 2p1/2-2s1/2 transition in lithiumlike uranium.

Persson, Hans; Lindgren, Ingvar; Salomonson, Sten; Sunnergren, Per

1993-10-01

359

Efficient and accurate fragmentation methods.  

PubMed

Conspectus Three novel fragmentation methods that are available in the electronic structure program GAMESS (general atomic and molecular electronic structure system) are discussed in this Account. The fragment molecular orbital (FMO) method can be combined with any electronic structure method to perform accurate calculations on large molecular species with no reliance on capping atoms or empirical parameters. The FMO method is highly scalable and can take advantage of massively parallel computer systems. For example, the method has been shown to scale nearly linearly on up to 131?000 processor cores for calculations on large water clusters. There have been many applications of the FMO method to large molecular clusters, to biomolecules (e.g., proteins), and to materials that are used as heterogeneous catalysts. The effective fragment potential (EFP) method is a model potential approach that is fully derived from first principles and has no empirically fitted parameters. Consequently, an EFP can be generated for any molecule by a simple preparatory GAMESS calculation. The EFP method provides accurate descriptions of all types of intermolecular interactions, including Coulombic interactions, polarization/induction, exchange repulsion, dispersion, and charge transfer. The EFP method has been applied successfully to the study of liquid water, ?-stacking in substituted benzenes and in DNA base pairs, solvent effects on positive and negative ions, electronic spectra and dynamics, non-adiabatic phenomena in electronic excited states, and nonlinear excited state properties. The effective fragment molecular orbital (EFMO) method is a merger of the FMO and EFP methods, in which interfragment interactions are described by the EFP potential, rather than the less accurate electrostatic potential. The use of EFP in this manner facilitates the use of a smaller value for the distance cut-off (Rcut). Rcut determines the distance at which EFP interactions replace fully quantum mechanical calculations on fragment-fragment (dimer) interactions. The EFMO method is both more accurate and more computationally efficient than the most commonly used FMO implementation (FMO2), in which all dimers are explicitly included in the calculation. While the FMO2 method itself does not incorporate three-body interactions, such interactions are included in the EFMO method via the EFP self-consistent induction term. Several applications (ranging from clusters to proteins) of the three methods are discussed to demonstrate their efficacy. The EFMO method will be especially exciting once the analytic gradients have been completed, because this will allow geometry optimizations, the prediction of vibrational spectra, reaction path following, and molecular dynamics simulations using the method. PMID:24810424

Pruitt, Spencer R; Bertoni, Colleen; Brorsen, Kurt R; Gordon, Mark S

2014-09-16

360

NANOMATERIALS FOR PROTEIN MEDIATED THERAPY AND DELIVERY  

PubMed Central

There has been a significant amount of research done on liposomes and nanoparticles as drug carriers for protein drugs. Proteins and enzymes have been used both as targeting moieties and for their therapeutic potential. High specificity and rapid reaction rates make proteins and enzymes excellent candidates for therapeutic treatment, but some limitations exist. Many of these limitations can be addressed by a well studied nanotechnology based delivery system. Such a system can provide a medium for delivery, stabilization of the drugs, and enable site specific accumulation of drugs. Nanomedicines such as these have great potential to revolutionize the pharmaceutical industry and improve healthcare worldwide. PMID:25414730

Barry, John N.; Vertegel, Alexey A.

2014-01-01

361

Protein-Based Nanomedicine Platforms for Drug Delivery  

SciTech Connect

Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein based drug delivery system.

Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong; Wang, Jun; Lin, Yuehe

2009-08-03

362

Biopolymeric alginate-chitosan nanoparticles as drug delivery carriers for cancer therapy.  

PubMed

Nanoparticulate drug delivery systems enhance cancer treatment by direct entry of nanometer particles into the fenestration in the vasculature of cancer cells. Nanoparticles for encapsulation of anticancer drugs are preferably prepared using natural polymers as carriers, with polysaccharides being particularly favorable. Alginate and chitosan polysaccharides have been widely used in nanoparticulate drug delivery systems because of their biodegradable, biocompatible, non-toxic and bioadhesive properties. In this review, we present an overview of drug delivery systems for cancer treatment, describe the use of biopolymeric alginate-chitosan nanoparticles for anticancer drug delivery, and discuss the important characteristics of these nanoparticles for use in drug delivery. PMID:25158565

Bhunchu, S; Rojsitthisak, P

2014-08-01

363

Accurate shear measurement with faint sources  

NASA Astrophysics Data System (ADS)

For cosmic shear to become an accurate cosmological probe, systematic errors in the shear measurement method must be unambiguously identified and corrected for. Previous work of this series has demonstrated that cosmic shears can be measured accurately in Fourier space in the presence of background noise and finite pixel size, without assumptions on the morphologies of galaxy and PSF. The remaining major source of error is source Poisson noise, due to the finiteness of source photon number. This problem is particularly important for faint galaxies in space-based weak lensing measurements, and for ground-based images of short exposure times. In this work, we propose a simple and rigorous way of removing the shear bias from the source Poisson noise. Our noise treatment can be generalized for images made of multiple exposures through MultiDrizzle. This is demonstrated with the SDSS and COSMOS/ACS data. With a large ensemble of mock galaxy images of unrestricted morphologies, we show that our shear measurement method can achieve sub-percent level accuracy even for images of signal-to-noise ratio less than 5 in general, making it the most promising technique for cosmic shear measurement in the ongoing and upcoming large scale galaxy surveys.

Zhang, Jun; Luo, Wentao; Foucaud, Sebastien

2015-01-01

364

Nanoparticles for Pulmonary Delivery  

Microsoft Academic Search

\\u000a This chapter aims to provide a rational for the use of nanoparticles in pulmonary delivery as well as an overview of strategies\\u000a and physiological implications of nanoparticle delivery to the lungs. Formulation aspects of nanoparticle systems in the form\\u000a of liquid dispersions and inhaled dry powders are also reviewed. The chapter also addresses the expanse of lung toxicology\\u000a research surrounding

Alan B. Watts; Robert O. Williams

365

Current perspectives on intrathecal drug delivery  

PubMed Central

Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes. PMID:25395870

Bottros, Michael M; Christo, Paul J

2014-01-01

366

Targeted delivery of therapeutics to endothelium  

PubMed Central

The endothelium is a target for therapeutic and diagnostic interventions in a plethora of human disease conditions including ischemia, inflammation, edema, oxidative stress, thrombosis and hemorrhage, and metabolic and oncological diseases. Unfortunately, drugs have no affinity to the endothelium, thereby limiting the localization, timing, specificity, safety, and effectiveness of therapeutic interventions. Molecular determinants on the surface of resting and pathologically altered endothelial cells, including cell adhesion molecules, peptidases, and receptors involved in endocytosis, can be used for drug delivery to the endothelial surface and into intracellular compartments. Drug delivery platforms such as protein conjugates, recombinant fusion constructs, targeted liposomes, and stealth polymer carriers have been designed to target drugs and imaging agents to these determinants. We review endothelial target determinants and drug delivery systems, describe parameters that control the binding of drug carriers to the endothelium, and provide examples of the endothelial targeting of therapeutic enzymes designed for the treatment of acute vascular disorders including ischemia, oxidative stress, inflammation, and thrombosis. PMID:18815813

Simone, Eric; Ding, Bi-Sen

2009-01-01

367

Comparison of Elekta VMAT with helical tomotherapy and fixed field IMRT: Plan quality, delivery efficiency and accuracy  

SciTech Connect

Purpose: Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are arc-based approaches to IMRT delivery. The objective of this study is to compare VMAT to both HT and fixed field IMRT in terms of plan quality, delivery efficiency, and accuracy. Methods: Eighteen cases including six prostate, six head-and-neck, and six lung cases were selected for this study. IMRT plans were developed using direct machine parameter optimization in the Pinnacle{sup 3} treatment planning system. HT plans were developed using a Hi-Art II planning station. VMAT plans were generated using both the Pinnacle{sup 3} SmartArc IMRT module and a home-grown arc sequencing algorithm. VMAT and HT plans were delivered using Elekta's PreciseBeam VMAT linac control system (Elekta AB, Stockholm, Sweden) and a TomoTherapy Hi-Art II system (TomoTherapy Inc., Madison, WI), respectively. Treatment plan quality assurance (QA) for VMAT was performed using the IBA MatriXX system while an ion chamber and films were used for HT plan QA. Results: The results demonstrate that both VMAT and HT are capable of providing more uniform target doses and improved normal tissue sparing as compared with fixed field IMRT. In terms of delivery efficiency, VMAT plan deliveries on average took 2.2 min for prostate and lung cases and 4.6 min for head-and-neck cases. These values increased to 4.7 and 7.0 min for HT plans. Conclusions: Both VMAT and HT plans can be delivered accurately based on their own QA standards. Overall, VMAT was able to provide approximately a 40% reduction in treatment time while maintaining comparable plan quality to that of HT.

Rao Min; Yang Wensha; Chen Fan; Sheng Ke; Ye Jinsong; Mehta, Vivek; Shepard, David; Cao Daliang [Department of Radiation Oncology, Swedish Cancer Institute, 1221 Madison St., Seattle, Washington 98104 (United States); Department of Radiation Oncology, University of Virginia Health Systems, Charlottesville, Virginia 22908 (United States); Department of Radiation Oncology, Swedish Cancer Institute, 1221 Madison St., Seattle, Washington 98104 (United States); Department of Radiation Oncology, University of Virginia Health Systems, Charlottesville, Virginia 22908 (United States); Department of Radiation Oncology, Swedish Cancer Institute, 1221 Madison St., Seattle, Washington 98104 (United States)

2010-03-15

368

Accurate extraction of the News  

E-print Network

We propose a new scheme for extracting gravitational radiation from a characteristic numerical simulation of a spacetime. This method is similar in conception to our earlier work but analytical and numerical implementation is different. The scheme is based on direct transformation to the Bondi coordinates and the gravitational waves are extracted by calculating the Bondi news function in Bondi coordinates. The entire calculation is done in a way which will make the implementation easy when we use uniform Bondi angular grid at $\\mathcal I^+$. Using uniform Bondi grid for news calculation has added advantage that we have to solve only ordinary differential equations instead of partial differential equation. For the test problems this new scheme allows us to extract gravitational radiation much more accurately than the previous schemes.

Shrirang S. Deshingkar

2006-09-14

369

Guidelines for accurate TOD measurement  

NASA Astrophysics Data System (ADS)

Guidelines to perform Triangle Orientation Discrimination (TOD) measurements are given in the present paper. The optimal range of test pattern sizes and contrasts are specified, as well as the required number of presentations for a threshold estimate. Special attention is paid to the statistical analysis. A standard frequency-of-serving curve is fitted to the observer data in order to obtain 75%- correct thresholds. A (chi) 2-statistic provides an objective criterion for acceptance or rejection of the threshold estimates. Finally, a complete TOD curve is obtained by fitting a weighted least-square polynomial through the 75%-correct thresholds. Further, a simple Go- NoGo screening procedure with objective pass/fail criteria, based on the TOD methodology, is proposed. With the TOD methodology, accurate sensor performance measured and Go- NoGo testing have become very easy to carry out. Therefore, the investment in a thoroughly design measurement setup will apply itself back easily.

Bijl, Piet; Valeton, J. M.

1999-07-01

370

N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population  

PubMed Central

Background: Innovative Vision Products, Inc. (IVP)’s scientists developed the lubricant eye drops (Can-C™) designed as 1% N-acetylcarnosine (NAC) prodrug of l-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural l-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C™ eye drops. Objective and study design: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years. Setting: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients’ glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision. Patients or other participants: The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C™ eye drops since December 2001. Intervention: Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the patients’ compliance rate to self-administer NAC eye-drops. Main outcome measure and results: The ophthalmic drug showed potential for the non-surgical treatment of age-related cataracts for participants after controlling for age, gender and daily activities and on a combined basis of repurchases behavior reports in more than 50,000 various cohort survivors, has been demonstrated to have a high efficacy and good tolerability for prevention and treatment of visual impairment determined for the older population with relative stable pattern of causes for blindness and visual impairment. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase); prevention of carbohydrate and metal-catalyzed autooxidation of ascorbic acid-induced cross-linking glycation reactions to the lens proteins; transglycation properties of carnosine, allowing it to compete for the glycating agent, protecting proteins (lens crystallins) against modification; universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals; activation with l-carnosine ingredient of proteasome activity in the lens; chaperone-like disaggregating to lens crystallins activity of NAC and of its bioactivated principal carnosine. Blindness incidence increased with advancing age, such as cataract and glaucoma, which are by far the commonest causes of blindness in our sample and in all age groups, glaucomatous neurodegeneration can be treated with developed NAC autoinduction prodrug eye drops equipped with corneal absorption promoters. The common blinding affections presenting in developed countries such as, senile macular degeneration, hereditary chorioretinal dystrophies, diabetic retinopathy are poorly represented in our current summary of vital

Babizhayev, Mark A; Burke, Leslie; Micans, Philip; Richer, Stuart P

2009-01-01

371

Clinical applications of biomedical microdevices for controlled drug delivery.  

PubMed

Miniaturization of devices to micrometer and nanometer scales, combined with the use of biocompatible and functional materials, has created new opportunities for the implementation of drug delivery systems. Advances in biomedical microdevices for controlled drug delivery platforms promise a new generation of capabilities for the treatment of acute conditions and chronic illnesses, which require high adherence to treatment, in which temporal control over the pharmacokinetic profiles is critical. In addition, clinical conditions that require a combination of drugs with specific pharmacodynamic profiles and local delivery will benefit from drug delivery microdevices. This review provides a summary of various clinical applications for state-of-the-art controlled drug delivery microdevices, including cancer, endocrine and ocular disorders, and acute conditions such as hemorrhagic shock. Regulatory considerations for clinical translation of drug delivery microdevices are also discussed. Drug delivery microdevices promise a remarkable gain in clinical outcomes and a substantial social impact. A review of articles covering the field of microdevices for drug delivery was performed between January 1, 1990, and January 1, 2014, using PubMed as a search engine. PMID:25484235

Gurman, Pablo; Miranda, Oscar R; Clayton, Kevin; Rosen, Yitzhak; Elman, Noel M

2015-01-01

372

Carbohydrate Polymers for Nonviral Nucleic Acid Delivery  

PubMed Central

Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylen