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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

Platelets as delivery systems for disease treatments  

PubMed Central

Platelets are small, anucleate, discoid shaped blood cells that play a fundamental role in hemostasis. Platelets contain a large number of biologically active molecules within cytoplasmic granules that are critical to normal platelet function. Because platelets circulate in blood through out the body, release biological molecules and mediators on demand, and participate in hemostasis as well as many other pathophysiologic processes, targeting expression of proteins of interest to platelets and utilizing platelets as delivery systems for disease treatment would be a logical approach. This paper reviews the genetic therapy for inherited bleeding disorders utilizing platelets as delivery system, with a particular focus on platelet-derived FVIII for hemophilia A treatment.

Shi, Qizhen; Montgomery, Robert R.

2010-01-01

3

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.

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

2013-01-01

4

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

5

Breast cancer survivors accurately reported key treatment and prognostic characteristics  

Microsoft Academic Search

Background and objectiveMedical records are considered the gold standard for information on cancer treatments and prognosis. We compared survivor self-report and medical records for agreement on key treatment and prognostic characteristics.

Elizabeth Maunsell; Mélanie Drolet; Najwa Ouhoummane; Jean Robert

2005-01-01

6

Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control  

SciTech Connect

Purpose: Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. Methods and Materials: A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles with 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. Results: There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. Conclusions: SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.

Able, Charles M., E-mail: cable@wfubmc.edu [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Bright, Megan; Frizzell, Bart [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States)] [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States)

2013-03-01

7

Misoprostol vaginal insert for induction of labor: a delivery system with accurate dosing and rapid discontinuation.  

PubMed

Labor induction and cervical ripening are widely utilized and new methods are constantly being investigated. Prostaglandins have been shown to be effective labor induction agents and, in particular, were compared with other prostaglandin preparations; vaginal misoprostol used off-label was associated with reduced failure to achieve vaginal delivery. The challenge is to provide this medication with the correct dosing for this indication and with the ability to discontinue the medication if needed, all while ensuring essential maternal and neonatal safety. The misoprostol vaginal insert initiates cervical ripening using a delivery system that controls misoprostol release and can be rapidly removed. This article reviews the development, safety and efficacy of the misoprostol vaginal insert for induction of labor and cervical ripening, and will focus on vaginally administered prostaglandins. PMID:24328596

Stephenson, Megan L; Hawkins, J Seth; Powers, Barbara L; Wing, Deborah A

2014-01-01

8

Accurate treatment of coulomb contribution in nucleus-nuclues bremsstrahlung  

NASA Astrophysics Data System (ADS)

Partial-wave expansions of nucleus-nucleus bremsstrahlung cross sections converge very slowly as a function of orbital momentum, especially at small deflection angles. While nuclear effects can easily be restricted to a limited number of partial waves, Coulomb effects contribute to much higher partial waves because of the long range of the force. We accurately solve this problem by separating the bremsstrahlung matrix element into a purely Coulomb part and a fast-convergin series. The Coulomb contribution is calculated by numerically integrating analytical expressions of the Coulomb bremsstrahlung matrix element. The accuracy of the results and the importance of the corrections are studied in a potential-model description of the ?(?, ??)? reaction.

Baye, D.; Sauwens, C.; Descouvemont, P.; Keller, S.

1991-07-01

9

Advances in the delivery of treatments for Parkinson's disease.  

PubMed

Innovative drug delivery in Parkinson's disease (PD) has the potential to reduce or avoid many side effects of current treatment, such as wearing-off type fluctuations, dyskinesia, on-off phenomena or bouts of motor freezing. The traditional orally administered formulations of l-dihydroxyphenylalanine combined with a peripheral aromatic acid decarboxylase inhibitor remain the mainstay of treatments for PD. However, such combination therapies have been further formulated to extend their duration of action by including a catechol-O-methyltransferase inhibitor. Preventing the breakdown of dopamine has also been achieved by monoamine oxidase-B inhibition; this approach now having been formulated for sublingual use (Zelapar, Valeant Pharmaceuticals). An alternative approach bypasses the oral route of administration and instead relies on continuous duodenal infusion (Duodopa, Solvay, NeoPharma AB) for better therapeutic effect. The clinical use of dopamine agonists as antiparkinsonian drugs now incorporates a variety of delivery techniques. For example, apomorphine, which relies on parenteral administration for maximum bioavailability, may be delivered via rectal, intranasal, sublingual and subcutaneous (e.g., Apokyn, Mylan Bertek) routes. Meanwhile, rotigotine and lisuride have both been formulated for delivery via skin patches. Finally, the authors examine more experimental delivery techniques, including the delivery of genes via viral vectors or liposomes, intracranial transplant of a variety of cells and of L-dihydroxyphenylalanine by prodrug-dispensing liposomes or pulmonary delivery (AIR, Alkermes). The advent and application of these varied technologies will help encourage patient-specific means of treatment for PD. PMID:16296809

Johnston, Tom H; Fox, Susan H; Brotchie, Jonathan M

2005-11-01

10

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.

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

2014-01-01

11

Drug delivery systems for treatment of systemic hypertension.  

PubMed

Novel drug delivery systems are available in many areas of medicine. Their application in the treatment of hypertension continues to widen. Oral drug delivery systems permit antihypertensive agents that were previously administered two to four times daily to be administered once daily. Biotechnical use of chemical-dispensing systems has been applied to propranolol (polymer coated beads), clonidine (transdermal therapeutic system), nifedipine (osmotic pump and coat-core), isradipine (osmotic pump), verapamil (sodium alginate and spheroidal oral delivery absorption system), felodipine (coat-core), nisoldipine (coat-core) and diltiazem (polymer coated beads and Geomatrix. The initial goal was to lower blood pressure by a uniform amount throughout the entire day. Now, new drug delivery systems are being developed to target blood pressure in the early morning hours when most cardiovascular events occur. Two chronotherapeutic drug delivery systems are now available for verapamil (chronotherapeutic oral delivery absorption system and delayed coat osmotic pump). Disadvantages of sustained-release products include delayed achievement of pharmacodynamic effect, unpredictable bioavailability, enhanced first-pass hepatic metabolism, dose dumping, sustained toxicity, dosage inflexibility and increased cost. Potential advantages include reduced administration frequency, enhanced adherence and convenience, reduced toxicity, stable drug concentrations, uniform drug effect, decreased cost (occasionally) and decreased daily dosage. PMID:12908851

Prisant, L Michael; Elliott, William J

2003-01-01

12

Novel periodontal drug delivery system for treatment of periodontitis  

Microsoft Academic Search

A conceptually novel periodontal drug delivery system (DDS) is described that is intended for treatment of microbial infections associated with periodontitis. The DDS is a composite wafer with surface layers possessing adhesive properties, while the bulk layer consists of antimicrobial agents, biodegradable polymers, and matrix polymers. The wafers contain poly(lactic-co-glycolic acid) as the main bioerodible component used in the bulk

Lev E Bromberg; Debra K Buxton; Phillip M Friden

2001-01-01

13

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.

Vyas, Amber; Kumar Sonker, Avinesh

2014-01-01

14

Drug Delivery Implants in the Treatment of Vitreous Inflammation  

PubMed Central

The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article.

Wang, Jillian; Jiang, Angela; Joshi, Malav; Christoforidis, John

2013-01-01

15

Convection-Enhanced Delivery in the Treatment of Epilepsy  

PubMed Central

Summary Convection-enhanced delivery (CED) is a novel drug-delivery technique that uses positive hydrostatic pressure to deliver a fluid containing a therapeutic substance by bulk flow directly into the interstitial space within a localized region of the brain parenchyma. CED circumvents the blood-brain barrier and provides a wider, more homogenous distribution than bolus deposition (focal injection) or other diffusion-based delivery approaches. A potential use of CED is for the local delivery of antiseizure agents, which would provide an epilepsy treatment approach that avoids the systemic toxicities of orally administered antiepileptic drugs and bystander effects on non-epileptic brain regions. Recent studies have demonstrated that brief CED infusions of nondiffusible peptides that inhibit the release of excitatory neurotransmitters, including ?-conotoxins and botulinum neurotoxins, can produce long-lasting (weeks to months) seizure protection in the rat amygdala-kindling model. Seizure protection is obtainable without detectable neurological or behavioral side effects. Although conventional diffusible antiepileptic drugs do confer seizure protection when administered locally by CED, the effect is transitory. CED is a potential approach for seizure protection that could represent an alternative to resective surgery in the treatment of focal epilepsies that are resistant to orally-administered antiepileptic drugs. The prolonged duration of action of nondiffusible toxins would allow seizure protection to be maintained chronically with infrequent reinfusions.

Rogawski, Michael A.

2009-01-01

16

Treatment delivery platform for conformal catheter-based ultrasound hyperthermia  

NASA Astrophysics Data System (ADS)

A clinical treatment delivery platform has been developed for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. This integrated system consists of hardware and software components required for thermal therapy delivery, treatment monitoring and control, and realtime and post-treatment analysis; and interstitial and endocavity ultrasound heating applicators. Hardware includes a 32-channel RF amplifier with independent power (0-25 W) and frequency (5-10 MHz) control for ultrasound power delivery and a 48-channel thermometry system compatible with 0.4 mm OD multi-sensor thermocouple probes. Software graphical user interfaces (GUI) are used to monitor and control both the amplifier and the thermometry system. The amplifier GUI controls, monitors, and records individual channel frequency and power values in real-time; the thermometry GUI monitors and records temperature and thermal dose values in real-time, as well as displaying and allowing dynamic control for temperature and thermal dose target thresholds. The thermometry GUI also incorporates registration of thermocouple positions relative to target anatomy and applicator transducers based on HDR planning tools (CT/MRI/US overlays) for improved treatment control and documentation. The interstitial (2.4 mm) and endocavity (6 mm) ultrasound hyperthermia applicators are composed of linear arrays of 1-4 tubular piezoceramic transducers - sectored at 90°, 180°, 270°, and 360° for single or dual directional heating patterns - that are compatible with plastic implant catheters. QA techniques specific to these catheter-based ultrasound applicators have been devised and implemented, and include rotational beam plots and dynamic force balance efficiency measurements, which are critical to establish applicator performance. A quality assurance test matrix has been devised and used to evaluate and characterize all components of this system prior to clinical implementation.

Juang, Titania; Wootton, Jeffery; Hsu, I.-Chow; Diederich, Chris

2009-02-01

17

Drug delivery with carbon nanotubes for in vivo cancer treatment  

PubMed Central

Chemically functionalized single-walled carbon nanotubes (SWNTs) have shown promise in tumor targeted accumulation in mice and exhibit biocompatibility, excretion and little toxicity. Here, we demonstrate in-vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug to branched polyethylene-glycol (PEG) chains on SWNTs via a cleavable ester bond to obtain a water soluble SWNT-paclitaxel conjugate (SWNT-PTX). SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol® in a murine 4T1 breast-cancer model, owing to prolonged blood circulation and 10-fold higher tumor PTX uptake by SWNT delivery likely through enhanced permeability and retention (EPR). Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via biliary pathway without causing obvious toxic effects to normal organs. Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses.

Liu, Zhuang; Chen, Kai; Davis, Corrine; Sherlock, Sarah; Cao, Qizhen; Chen, Xiaoyuan; Dai, Hongjie

2008-01-01

18

Logic Regression for Provider Effects on Kidney Cancer Treatment Delivery  

PubMed Central

In the delivery of medical and surgical care, often times complex interactions between patient, physician, and hospital factors influence practice patterns. This paper presents a novel application of logic regression in the context of kidney cancer treatment delivery. Using linked data from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program and Medicare we identified patients diagnosed with kidney cancer from 1995 to 2005. The primary endpoints in the study were use of innovative treatment modalities, namely, partial nephrectomy and laparoscopy. Logic regression allowed us to uncover the interplay between patient, provider, and practice environment variables, which would not be possible using standard regression approaches. We found that surgeons who graduated in or prior to 1980 despite having some academic affiliation, low volume surgeons in a non-NCI hospital, or surgeons in rural environment were significantly less likely to use laparoscopy. Surgeons with major academic affiliation and practising in HMO, hospital, or medical school based setting were significantly more likely to use partial nephrectomy. Results from our study can show efforts towards dismantling the barriers to adoption of innovative treatment modalities, ultimately improving the quality of care provided to patients with kidney cancer.

Banerjee, Mousumi; Filson, Christopher; Xia, Rong; Miller, David C.

2014-01-01

19

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

20

Evaluation of Interacavitary Chemotherapy Delivery for Treatment of Mammary Carcinoma.  

National Technical Information Service (NTIS)

This project evaluated paclitaxel chemotherapy delivery from a gel polymer system placed into a wound bed following conservative (marginal) surgical removal of human breast cancers grown in nude mice. This delivery method was shown to control local tumor ...

W. S. Dernell

2005-01-01

21

Evaluation of Intracavitary Chemotherapy Delivery for Treatment of Mammary Carcinoma.  

National Technical Information Service (NTIS)

This project will evaluate paclitaxel chemotherapy delivery from a gel polymer system placed into a wound bed following conservative (marginal) surgical removal of human breast cancers grown in nude mice. This delivery method is proposed to control local ...

W. S. Dernell

2004-01-01

22

Evaluation of Intracavitary Chemotherapy Delivery for Treatment of Mammary Carcinoma.  

National Technical Information Service (NTIS)

This project will evaluate paclitaxel chemotherapy delivery from a gel polymer system placed into a wound bed following conservative surgical removal of human breast cancers grown in nude mice. This novel delivery method is proposed to control local tumor...

W. S. Dernell

2003-01-01

23

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

24

The use of a realistic VMAT delivery emulator to optimize dynamic machine parameters for improved treatment efficiency  

NASA Astrophysics Data System (ADS)

The delivery of volumetric modulated arc therapy (VMAT) requires the simultaneous movement of the linear accelerator gantry, multi-leaf collimators and jaws while the dose rate is varied. In this study, a VMAT delivery emulator was developed to accurately predict the characteristics of a given treatment plan, incorporating realistic parameters for gantry inertia and the variation in leaf speed with respect to gravity. The emulator was used to assess the impact of dynamic machine parameters on the delivery efficiency, using a set of prostate and head and neck VMAT plans. Initially, assuming a VMAT system with fixed dose rate bins, the allowable leaf and jaw speeds were increased and a significant improvement in treatment time and average dose rate was observed. The software was then adapted to simulate a VMAT system with continuously varying dose rate, and the increase in delivery efficiency was quantified, along with the impact of an increased leaf and jaw speed. Finally, a set of optimal dynamic machine parameters was derived assuming an idealized scenario in which the treatment is delivered in a single arc at constant maximum gantry speed.

Boylan, C. J.; Rowbottom, C. G.; Mackay, R. I.

2011-07-01

25

Passive flow regulators for drug delivery and hydrocephalus treatment  

NASA Astrophysics Data System (ADS)

Passive flow regulators are usually intended to deliver or drain a fluid at a constant rate independently from pressure variations. New designs of passive flow regulators made of a stack of a silicon membrane anodically bonded to a Pyrex substrate are proposed. A first design has been built for the derivation of cerebrospinal fluid (CSF) towards peritoneum for hydrocephalus treatment. The device allows draining CSF at the patient production rate independently from postural changes. The flow rate is regulated at 20 ml/h in the range 10 to 40 mbar. Specific features to adjust in vivo the nominal flow rate are shown. A second design including high pressure shut-off feature has been made. The intended use is drug delivery with pressurized reservoir of typically 100 to 300 mbar. In both cases, the membrane comprises several holes facing pillars in the Pyrex substrate. These pillars are machined in a cavity which ensures a gap between the membrane and the pillars at rest. The fluid in the pressurized reservoir is directly in contact with the top surface of the membrane, inducing its deflection towards Pyrex substrate and closing progressively the fluidic pathway through each hole of the membrane. Since the membrane deflection is highly non-linear, FEM simulations have been performed to determine both radial position and diameter of the membrane holes that ensure a constant flow rate for a given range of pressure.

Chappel, E.; Dumont-Fillon, D.; Mefti, S.

2014-03-01

26

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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. PMID:24648369

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

2014-06-01

27

Convection-Enhanced Delivery for the Treatment of Pediatric Neurologic Disorders  

PubMed Central

Direct perfusion of specific regions of the central nervous system by convection-enhanced delivery is becoming more widely used for the delivery of compounds in the research and treatment of various neural disorders. In contrast to other currently available central nervous system delivery techniques, convection-enhanced delivery relies on bulk flow for distribution of solute. This allows for safe, targeted, reliable, and homogeneous delivery of small- and large-molecular-weight substances over clinically relevant volumes in a manner that bypasses the blood-central nervous system barrier. Recent studies have also shown that coinfused imaging surrogate tracers can be used to monitor and control the convective distribution of therapeutic agents in vivo. The unique features of convection-enhanced delivery, including the ability to monitor distribution in real-time, provide an opportunity to develop new research and treatment paradigms for pediatric patients with a variety of intrinsic central nervous system disorders.

Song, Debbie K.; Lonser, Russell R.

2013-01-01

28

Delivery of Healthcare at Military Treatment Facilities (MTFs).  

National Technical Information Service (NTIS)

This Instruction, under DoD Directive 5136.1, implement policy, assigns responsibilities and prescribes procedures on provisions of care in the delivery of healthcare at MTFs in the Military Health Services System; implements policy, assigns responsibilit...

M. Bonifas

1996-01-01

29

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.

Husseini, Ghaleb A.; Pitt, William G.

2008-01-01

30

Energy Delivery Systems for Treatment of Benign Prostatic Hyperplasia  

PubMed Central

Executive Summary Objective The Ontario Health Technology Advisory Committee asked the Medical Advisory Secretariat (MAS) to conduct a health technology assessment on energy delivery systems for the treatment of benign prostatic hyperplasia (BPH). Clinical Need: Target Population and Condition BPH is a noncancerous enlargement of the prostate gland and the most common benign tumour in aging men. (1) It is the most common cause of lower urinary tract symptoms (LUTS) and bladder outlet obstruction (BOO) and is an important cause of diminished quality of life among aging men. (2) The primary goal in the management of BPH for most patients is a subjective improvement in urinary symptoms and quality of life. Until the 1930s, open prostatectomy, though invasive, was the most effective form of surgical treatment for BPH. Today, the benchmark surgical treatment for BPH is transurethral resection of the prostate (TURP), which produces significant changes of all subjective and objective outcome parameters. Complications after TURP include hemorrhage during or after the procedure, which often necessitates blood transfusion; transurethral resection (TUR) syndrome; urinary incontinence; bladder neck stricture; and sexual dysfunction. A retrospective review of 4,031 TURP procedures performed by one surgeon between 1979 and 2003 showed that the incidence of complications was 2.4% for blood transfusion, 0.3% for TUR syndrome, 1.5% for hemostatic procedures, 2.8% for bladder neck contracture, and 1% for urinary stricture. However, the incidence of blood transfusion and TUR syndrome decreased as the surgeon’s skills improved. During the 1990s, a variety of endoscopic techniques using a range of energy sources have been developed as alternative treatments for BPH. These techniques include the use of light amplification by stimulated emission of radiation (laser), radiofrequency, microwave, and ultrasound, to heat prostate tissue and cause coagulation or vaporization. In addition, new electrosurgical techniques that use higher amounts of energy to cut, coagulate, and vaporize prostatic tissue have entered the market as competitors to TURP. The driving force behind these new treatment modalities is the potential of producing good hemostasis, thereby reducing catheterization time and length of hospital stay. Some have the potential to be used in an office environment and performed under local anesthesia. Therefore, these new procedures have the potential to rival TURP if their effectiveness is proven over the long term. The Technology Being Reviewed The following energy-based techniques were considered for assessment: transurethral electrovaporization of the prostate (TUVP) transurethral electrovapor resection of the prostate (TUVRP) transurethral electrovaporization of the prostate using bipolar energy (plasmakinetic vaporization of the prostate [PKVP]) visual laser ablation of the prostate (VLAP) transurethral ultrasound guided laser incision prostatectomy (TULIP) contact laser vaporization of the prostate (CLV) interstitial laser coagulation (ILC) holmium laser resection of the prostate (HoLRP) holmium laser enucleation of the prostate (HoLEP) holmium laser ablation of the prostate (HoLAP) potassium titanyl phosphate (KTP) laser transurethral microwave thermotherapy (TUMT) transurethral needle ablation (TUNA) Review Strategy A search of electronic databases (OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library, and the International Agency for Health Technology Assessment [INAHTA] database) was undertaken to identify evidence published from January 1, 2000 to June 21, 2006. The search was limited to English-language articles and human studies. The literature search identified 284 citations, of which 38 randomized controlled trials (RCTs) met the inclusion criteria. Since the application of high-power (80 W) KTP laser (photoselective vaporization of the prostate [PVP]) has been supported in the United States and has resulted in a rapid diffusion of this technology in the absence of any RCTs, th

2006-01-01

31

The Development of a Model of Outpatient Chemotherapy Delivery – Chemotherapy Basic Treatment Equivalent (CBTE)  

Microsoft Academic Search

The aims of this study were to study the patient-, tumour- and treatment-related factors that significantly impact on treatment episode duration for outpatient chemotherapy treatment delivery, and to develop a new measure of outpatient chemotherapy throughput that considers variations in treatment duration compared with the older measures of patients treated per day. A pilot study in our institution randomly measured

Geoff Delaney; Geoff Bin Jalaludin; Eugene Moylan; Michael Barton

2002-01-01

32

Reconstruction of applicator positions from multiple-view images for accurate superficial hyperthermia treatment planning  

NASA Astrophysics Data System (ADS)

In the current clinical practice, prior to superficial hyperthermia treatments (HT), temperature probes are placed in tissue to document a thermal dose. To investigate whether the painful procedure of catheter placement can be replaced by superficial HT planning, we study if the specific absorption rate (SAR) coverage is predictive for treatment outcome. An absolute requirement for such a study is the accurate reconstruction of the applicator setup. The purpose of this study was to investigate the feasibility of the applicator setup reconstruction from multiple-view images. The accuracy of the multiple-view reconstruction method has been assessed for two experimental setups using six lucite cone applicators (LCAs) representing the largest array applied at our clinic and also the most difficult scenario for the reconstruction. For the two experimental setups and 112 distances, the mean difference between photogrametry reconstructed and manually measured distances was 0.25 ± 0.79 mm (mean±1 standard deviation). By a parameter study of translation T (mm) and rotation R (°) of LCAs, we showed that these inaccuracies are clinically acceptable, i.e. they are either from ±1.02 mm error in translation or ±0.48° in rotation, or combinations expressed by 4.35R2 + 0.97T2 = 1. We anticipate that such small errors will not have a relevant influence on the SAR distribution in the treated region. The clinical applicability of the procedure is shown on a patient with a breast cancer recurrence treated with reirradiation plus superficial hyperthermia using the six-LCA array. The total reconstruction procedure of six LCAs from a set of ten photos currently takes around 1.5 h. We conclude that the reconstruction of superficial HT setup from multiple-view images is feasible and only minor errors are found that will have a negligible influence on treatment planning quality.

Drizdal, T.; Paulides, M. M.; Linthorst, M.; van Rhoon, G. C.

2012-05-01

33

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

34

CPR methodology with new steady-state criterion and more accurate statistical treatment of channel bow  

SciTech Connect

An overview is given of existing CPR design criteria and the methods used in BWR reload analysis to evaluate the impact of channel bow on CPR margins. Potential weaknesses in today's methodologies are discussed. Westinghouse in collaboration with KKL and Axpo - operator and owner of the Leibstadt NPP - has developed an optimized CPR methodology based on a new criterion to protect against dryout during normal operation and with a more rigorous treatment of channel bow. The new steady-state criterion is expressed in terms of an upper limit of 0.01 for the dryout failure probability per year. This is considered a meaningful and appropriate criterion that can be directly related to the probabilistic criteria set-up for the analyses of Anticipated Operation Occurrences (AOOs) and accidents. In the Monte Carlo approach a statistical modeling of channel bow and an accurate evaluation of CPR response functions allow the associated CPR penalties to be included directly in the plant SLMCPR and OLMCPR in a best-estimate manner. In this way, the treatment of channel bow is equivalent to all other uncertainties affecting CPR. Emphasis is put on quantifying the statistical distribution of channel bow throughout the core using measurement data. The optimized CPR methodology has been implemented in the Westinghouse Monte Carlo code, McSLAP. The methodology improves the quality of dryout safety assessments by supplying more valuable information and better control of conservatisms in establishing operational limits for CPR. The methodology is demonstrated with application examples from the introduction at KKL. (authors)

Baumgartner, S. [Axpo AG, Parkstrasse 23, CH-5401 Baden (Switzerland); Bieli, R. [Kernkraftwerk Leibstadt AG, CH-5325 Leibstadt (Switzerland); Bergmann, U. C. [Westinghouse Electric Sweden AB, SE-721 63 Vaesteraas (Sweden)

2012-07-01

35

A Review of the Effects of Medication Delivery Systems on Treatment Adherence in Children with Asthma  

PubMed Central

Background: A patient's adherence to an appropriate treatment regimen is necessary to minimize morbidity and mortality associated with childhood asthma. Many factors influence the success of treatment adherence. Objective: The goal of this article was to examine the effect of the mode of medication delivery on the success of treatment adherence in children with asthma. Methods: Relevant clinical studies were identified through a MEDLINE search of articles published from 1966 to 2002, using the search terms adherence, aerosol, asthma, children, compliance, dry powder inhaler, metered-dose inhaler, nebulizer, and pediatric. Results: A relationship seems to exist between treatment adherence and the type of medication delivery system used in childhood asthma. The highest rates of adherence appear to be associated with oral medications. Conclusions: Clinicians should consider the mode of medication delivery as 1 factor that can influence the success of treatment adherence.

Cohn, Robert C

2003-01-01

36

A New Method for Accurate Treatment of Flow Equations in Cylindrical Coordinates Using Series Expansions  

NASA Technical Reports Server (NTRS)

The motivation of this work is the ongoing effort at the Center for Turbulence Research (CTR) to use large eddy simulation (LES) techniques to calculate the noise radiated by jet engines. The focus on engine exhaust noise reduction is motivated by the fact that a significant reduction has been achieved over the last decade on the other main sources of acoustic emissions of jet engines, such as the fan and turbomachinery noise, which gives increased priority to jet noise. To be able to propose methods to reduce the jet noise based on results of numerical simulations, one first has to be able to accurately predict the spatio-temporal distribution of the noise sources in the jet. Though a great deal of understanding of the fundamental turbulence mechanisms in high-speed jets was obtained from direct numerical simulations (DNS) at low Reynolds numbers, LES seems to be the only realistic available tool to obtain the necessary near-field information that is required to estimate the acoustic radiation of the turbulent compressible engine exhaust jets. The quality of jet-noise predictions is determined by the accuracy of the numerical method that has to capture the wide range of pressure fluctuations associated with the turbulence in the jet and with the resulting radiated noise, and by the boundary condition treatment and the quality of the mesh. Higher Reynolds numbers and coarser grids put in turn a higher burden on the robustness and accuracy of the numerical method used in this kind of jet LES simulations. As these calculations are often done in cylindrical coordinates, one of the most important requirements for the numerical method is to provide a flow solution that is not contaminated by numerical artifacts. The coordinate singularity is known to be a source of such artifacts. In the present work we use 6th order Pade schemes in the non-periodic directions to discretize the full compressible flow equations. It turns out that the quality of jet-noise predictions using these schemes is especially sensitive to the type of equation treatment at the singularity axis. The objective of this work is to develop a generally applicable numerical method for treating the singularities present at the polar axis, which is particularly suitable for highly accurate finite-differences schemes (e.g., Pade schemes) on non-staggered grids. The main idea is to reinterpret the regularity conditions developed in the context of pseudo-spectral methods. A set of exact equations at the singularity axis is derived using the appropriate series expansions for the variables in the original set of equations. The present treatment of the equations preserves the same level of accuracy as for the interior scheme. We also want to point out the wider utility of the method, proposed here in the context of compressible flow equations, as its extension for incompressible flows or for any other set of equations that are solved on a non-staggered mesh in cylindrical coordinates with finite-differences schemes of various level of accuracy is straightforward. The robustness and accuracy of the proposed technique is assessed by comparing results from simulations of laminar forced-jets and turbulent compressible jets using LES with similar calculations in which the equations are solved in Cartesian coordinates at the polar axis, or in which the singularity is removed by employing a staggered mesh in the radial direction without a mesh point at r = 0.

Constantinescu, G.S.; Lele, S. K.

2000-01-01

37

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.

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

2013-01-01

38

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

PubMed

Human skin not only functions as a permeation barrier (mainly because of 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 especially chitosan, followed by those made of synthetic, degradable (aliphatic polyesters), and nondegradable (polyacrylates) 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 nanosized 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

39

Various non-injectable delivery systems for the treatment of diabetes mellitus.  

PubMed

Diabetes mellitus (diabetes) is suffered by more than 180 million people and is responsible for approximately 2.9 million deaths each year. This mortality rate is expected to increase by 50 % in the next decade. Due to the inconvenience of the traditional treatment of diabetes by subcutaneous administration of insulin injection, various attempts are made in the production, purification, formulation and methods of delivery of insulin. However, despite advances in recent years, these attempts have met with limited success. Various alternative routes such as rectal, ocular, nasal, pulmonary and oral have been exploited. The pulmonary route offers great potential for the delivery of polypeptide drugs due to the large surface area for insulin absorption in the respiratory tract. But due to its low bioavailability, oral route is intensely investigated for the insulin delivery. Microencapsulation, as one of the delivery systems utilising oral route, has shown some potential progress in insulin delivery; though it is at an early stage yet it has proved to be quite encouraging providing new less toxic immunosuppressive agents. Microencapsulation may prove to be an attractive delivery system for controlled release of insulin and beneficial for therapeutic, bio-efficient and bio-effective drug delivery. In this review we discuss the possible alternative routes for insulin delivery (ocular, nasal, pulmonary and oral) and advantages and disadvantages of each. Furthermore we consider the different drug delivery strategies available (aerosols, dry powder inhalers, synthetic beta cells, hydrogels and microcapsules) and their current and potential applications with respect to the different insulin delivery routes. PMID:19275677

Yadav, Neha; Morris, Gordon; Harding, S E; Ang, Shirley; Adams, G G

2009-03-01

40

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

41

Liposome based delivery systems in pancreatic cancer treatment: from bench to bedside.  

PubMed

Despite rapid advances in cancer diagnosis and treatment, pancreatic cancer remains one of the most difficult human malignancies to be treated, with a mortality rate nearly equal to its incidence. Although gemcitabine has been established as the standard first-line treatment for advanced pancreatic cancer, gemcitabine-based combination chemotherapy showed either marginal or no improvement in survival. Developments in liposomal delivery systems have facilitated the targeting of specific agents for cancer treatment. Such systems could be developed as platforms for future multi-functional theranostic nanodevices tailor-made for the combined detection of early cancer and functional drug delivery. We systemically review liposome based drug-delivery systems, which can provide improved pharmacokinetics, reduced side effects and potentially increased tumor uptake, for pancreatic cancer therapy. Novel liposomal formulations allowing for higher tumor targeting efficiencies and used in current clinical trials to treat this challenging disease are emphasized. PMID:21330062

Yang, Feng; Jin, Chen; Jiang, Yongjian; Li, Ji; Di, Yang; Ni, Quanxing; Fu, Deliang

2011-12-01

42

Delivery of EPC embedded in HA-hydrogels for treatment of acute kidney injury  

PubMed Central

Adoptive transfer of stem cells has shown potential as an effective treatment for acute kidney injury (AKI). The current strategy for adoptive transfer of stem cells is by intravenous injection. However, this conventional method of stem cell delivery is riddled with problems causing reduced efficacy of the therapeutic potential of delivered stem cells. This review summarizes the recent advancements in an alternative method of stem cell delivery for treatment of AKI, embedding stem cells in hyaluronic acid (HA-) based hydrogels followed by their implantation. Furthermore, one stem cell type in particular, endothelial progenitor cells (EPC), have shown remarkable therapeutic benefits for treatment of AKI when delivered by HA-hydrogels. The review also summarizes the delivery of EPC by HA-hydrogels in the setting of AKI.

Ratliff, Brian B.; Goligorsky, Michael S.

2013-01-01

43

Image-Guided Convection-Enhanced Delivery Platform in the Treatment of Neurological Diseases  

PubMed Central

Summary Convection-enhanced delivery (CED) of substances within the human brain is becoming a more frequent experimental treatment option in the management of brain tumors, and more recently in Phase 1 trials for gene therapy in Parkinson’s disease (PD). Benefits of this intracranial drug-transfer technology include a more efficient delivery of large volumes of therapeutic agent to the target region when compared to more standard delivery approaches (biopolymers, local infusion). In this article we describe specific technical modifications we have made to the CED process to make it more effective. For example, we developed a reflux-resistant infusion cannula that allows increased infusion rates to be used. We also describe our efforts to visualize the CED process in vivo, utilizing liposomal nanotechnology and real-time intraoperative MRI. In addition to carrying the MRI contrast agent, nanoliposomes also provide a standardized delivery vehicle for the convection of drugs to a specific brain tissue volume. Such technology provides an added level of assurance via visual confirmation of CED, allowing intra-operative alterations to the infusion if there is reflux or aberrant delivery. We propose that these specific modifications to the CED technology will improve efficacy by documenting and standardizing the treatment volume delivery. Furthermore, we believe that this image-guided CED platform can be utilized in other translational neuroscience efforts, with eventual clinical application beyond neuro-oncology and PD.

Fiandaca, Massimo S.; Forsayeth, John R.; Dickinson, Peter J.; Bankiewicz, Krystof S.

2009-01-01

44

Accurate Pain Detection Is Not Enough: Contextual and Attributional Style as Biasing Factors in Patient Evaluations and Treatment Choice1  

Microsoft Academic Search

Ninety-six adults with a supportive or unsupportive attributional style participated in an experiment that examined the effects of contextual (i.e., coping and medical evidence) information on evaluations of pain severity, the pain sufferer, and treatment choice for shoulder pain patients. Respondents accurately detected a patient's pain level from the vid­ eotaped facial displays, but patients who were coping with the

Linda M. Lundquist; N. C. Higgins; Kenneth M. Prkachin

2007-01-01

45

Large-scale extraction of accurate drug-disease treatment pairs from biomedical literature for drug repurposing  

PubMed Central

Background A large-scale, highly accurate, machine-understandable drug-disease treatment relationship knowledge base is important for computational approaches to drug repurposing. The large body of published biomedical research articles and clinical case reports available on MEDLINE is a rich source of FDA-approved drug-disease indication as well as drug-repurposing knowledge that is crucial for applying FDA-approved drugs for new diseases. However, much of this information is buried in free text and not captured in any existing databases. The goal of this study is to extract a large number of accurate drug-disease treatment pairs from published literature. Results In this study, we developed a simple but highly accurate pattern-learning approach to extract treatment-specific drug-disease pairs from 20 million biomedical abstracts available on MEDLINE. We extracted a total of 34,305 unique drug-disease treatment pairs, the majority of which are not included in existing structured databases. Our algorithm achieved a precision of 0.904 and a recall of 0.131 in extracting all pairs, and a precision of 0.904 and a recall of 0.842 in extracting frequent pairs. In addition, we have shown that the extracted pairs strongly correlate with both drug target genes and therapeutic classes, therefore may have high potential in drug discovery. Conclusions We demonstrated that our simple pattern-learning relationship extraction algorithm is able to accurately extract many drug-disease pairs from the free text of biomedical literature that are not captured in structured databases. The large-scale, accurate, machine-understandable drug-disease treatment knowledge base that is resultant of our study, in combination with pairs from structured databases, will have high potential in computational drug repurposing tasks.

2013-01-01

46

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.

Goncalez, M. L.; Correa, M. A.; Chorilli, M.

2013-01-01

47

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

48

Intranasal delivery of antiepileptic medications for treatment of seizures  

Microsoft Academic Search

Summary  Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are all deemed medical emergencies. Mortality\\u000a and worse neurologic outcome are directly associated with the duration of seizure activity. A number of recent reviews have\\u000a described consensus statements regarding the pharmacologic treatment protocols for seizures when patients are in pre-hospital,\\u000a institutional, and home-bound settings. Benzodiazepines, such as lorazepam, diazepam, midazolam,

Daniel P. Wermeling

2009-01-01

49

Iontophoresis-targeted, follicular delivery of minoxidil sulfate for the treatment of alopecia.  

PubMed

Although minoxidil (MX) is a drug known to stimulate hair growth, the treatment of androgenic alopecia could be improved by delivery strategies that would favor drug accumulation into the hair follicles. This work investigated in vitro the potential of iontophoresis to achieve this objective using MX sulfate (MXS), a more water-soluble derivative of MX. Passive delivery of MXS was first determined from an ethanol-water solution and from a thermosensitive gel. The latter formulation resulted in greater accumulation of MXS in the stratum corneum (skin's outermost layer) and hair follicles and an overall decrease in absorption through the skin. Anodal iontophoresis of MXS from the same gel formulation was then investigated at pH 3.5 and pH 5.5. Compared with passive delivery, iontophoresis increased the amount of drug reaching the follicular infundibula from 120 to 600 ng per follicle. In addition, drug recovery from follicular casts was threefold higher following iontophoresis at pH 5.5 compared with that at pH 3.5. Preliminary in vivo experiments in rats confirmed that iontophoretic delivery of MXS facilitated drug accumulation in hair follicles. Overall, therefore, iontophoresis successfully and significantly enhanced follicular delivery of MX suggesting a useful opportunity for the improved treatment of alopecia. PMID:23450524

Gelfuso, Guilherme Martins; Gratieri, Tais; Delgado-Charro, M Begoña; Guy, Richard H; Vianna Lopez, Renata Fonseca

2013-05-01

50

Importance of accurate dose calculations outside segment edges in intensity modulated radiotherapy treatment planning  

Microsoft Academic Search

Background and purpose: To assess the effect of differences in the calculation of the dose outside segment edges on the overall dose distribution and the optimisation process of intensity modulated radiation therapy (IMRT) treatment plans. Patients and methods: Accuracy of dose calculations of two treatment planning systems (TPS1 and TPS2) was assessed, to ensure that they are both suitable for

Marco Schwarz; Luc J. Bos; Ben J. Mijnheer; Joos V. Lebesque; Eugene M. F. Damen

2003-01-01

51

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.

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

2013-01-01

52

Treatment of intermediate stage hepatocellular carcinoma: a review of intrahepatic doxorubicin drug-delivery systems.  

PubMed

The biopharmaceutical properties of doxorubicin delivered via two drug-delivery systems (DDSs) for the palliative treatment of unresectable hepatocellular carcinoma were reviewed with relation to the associated liver and tumor (patho)physiology. These two DDSs, doxorubicin emulsified with Lipiodol(®) and doxorubicin loaded into DC Bead(®) are different regarding tumor delivery, release rate, local bioavailability, if and how they can be given repeatedly, biodegradability, length of embolization and safety profile. There have been few direct head-to-head comparisons of these DDSs, and in-depth investigations into their in vitro and in vivo performance is warranted. PMID:24856170

Dubbelboer, Ilse R; Lilienberg, Elsa; Ahnfelt, Emelie; Sjögren, Erik; Axén, Niklas; Lennernäs, Hans

2014-04-01

53

A new method for accurate assessment of DNA quality after bisulfite treatment  

PubMed Central

The covalent addition of methylgroups to cytosine has become the most intensively researched epigenetic DNA marker. The vast majority of technologies used for DNA methylation analysis rely on a chemical reaction, the so-called ‘bisulfite treatment’, which introduces methylation-dependent sequence changes through selective chemical conversion of non-methylated cytosine to uracil. After treatment, all non-methylated cytosine bases are converted to uracil but all methylated cytosine bases remain cytosine. These methylation dependent C-to-T changes can subsequently be studied using conventional DNA analysis technologies. The bisulfite conversion protocol is susceptible to processing errors, and small deviation from the protocol can result in failure of the treatment. Several attempts have been made to simplify the procedure and increase its robustness. Although significant achievements in this area have been made, bisulfite treatment remains the main source of process variability in the analysis of DNA methylation. This variability in particular impairs assays, which strive for the quantitative assessment of DNA methylation. Here we present basic mathematical considerations, which should be taken into account when analyzing DNA methylation. We also introduce a PCR-based assay, which allows ab initio assessment of the DNA quality after bisulfite treatment and can help to prevent inaccurate quantitative measurement resulting from poor bisulfite treatment.

Ehrich, Mathias; Zoll, Scott; Sur, Sudipto; van den Boom, Dirk

2007-01-01

54

Local drug delivery for treatment of coronary and peripheral artery disease.  

PubMed

Local drug delivery (LDD), the direct application of a therapeutic agent to a focal location, has been used in cardiovascular interventions to prophylactically reduce neointimal hyperplasia and relieve clot burden. LDD allows targeted use of drugs whose toxicities inhibit their systemic use while stent delivery allows for consistent and prolonged delivery. Stents eluting limus family drugs or paclitaxel inhibit vascular smooth muscle cell hyperplasia and migration and clinical use of such stents have reduced restenosis rates after percutaneous coronary procedures. However, associated with the increased efficacy is an increased rate of late stent thrombosis associated with death and myocardial infarction. Recent innovations, including bioabsorbable polymers and completely bioabsorbable stents may expand the use of drug-eluting stents. In this review, we discuss the development, the clinical use, and the effects of LDD from balloon and stent-based platforms in the treatment of restenosis and thrombus. PMID:20553281

Gertz, Zachary M; Wilensky, Robert L

2011-12-01

55

IV-1?Accurate Targeting for LIPUS (Low Intensity Pulsed Ultrasound) Treatment with Ultrasonography.  

PubMed

The LIPUS device is self-administered by patients and the quantity and accuracy of daily treatment may be important for fracture healing. We characterized the quantity of treatment as the LIPUS compliance ratio. However, there remains doubt as to the accuracy of the targeting point. We typically indicate target points on the patients' skin, determined from radiograms taken over with clips near the surgical wound. Especially in the case of femoral fracture with thick soft tissue, it can be difficult to estimate accuracy of the treatment point. We used ultrasonography to visualize the fracture line clearly and to show the location of the treatment point. In most cases, we were able to visualize fractures easily and to demonstrate to patients how to use the transducer. The greatest advantage of ultrasonography is that we can inspect and estimate the fracture line with patients and thereby raise patient motivation. Targeting by ultrasonography is a simple and effective method that may improve both the quantity and the quality of LIPUS treatment. PMID:24854471

Matsumura, Tomohiro; Saito, Tomohiro

2014-06-01

56

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.

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

2006-01-01

57

Developments in treatments for amyotrophic lateral sclerosis via intracerebroventricular or intrathecal delivery.  

PubMed

Introduction: Amyotrophic lateral scleroses (ALS) are neurodegenerative disorders primarily affecting the motor system. These incurable disorders are relentlessly progressive and typically limit survival to 2 - 5 years after disease onset. An improved knowledge about disease-causing genes, disease proteins and pathways has revealed considerable heterogeneity in ALS. Novel targeted therapies are being developed, but getting these beyond the BBB remains a challenge. Areas covered: The authors review the intracerebroventricular and intrathecal delivery of drugs for the treatment of ALS in preclinical and clinical studies. Expert opinion: Lack of BBB permeability should not hold back the development of promising treatments for ALS, as the available evidence suggest that direct intrathecal or intracerebroventricular administration of drug is a feasible delivery route in patients with ALS. PMID:24816247

Van Damme, Philip; Robberecht, Wim

2014-07-01

58

Delivery of Intraocular Triamcinolone Acetonide in the Treatment of Macular Edema  

PubMed Central

Macular edema (ME) is one of the eventual outcomes of various intraocular and systemic pathologies. The pathogenesis for ME is not yet entirely understood; however, some of the common risk factors for its development have been identified. While this investigation will not discuss the numerous etiologies of ME in detail, it appraises the two most widely studied delivery modalities of intraocular corticosteroids in the treatment of ME—intravitreal injection (IVI) and sub-Tenon’s infusion (STI). A thorough review of the medical literature was conducted to identify the efficacy and safety of IVI and STI, specifically for the administration of triamcinolone acetonide (TA), in the setting of ME in an attempt to elucidate a preferred steroid delivery modality for treatment of ME.

Pickrell, Aaron; Harris, Alon; Ngo, Sandra; Amireskandari, Annahita; Stewart, Erin; Siesky, Brent

2012-01-01

59

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

60

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.

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

2014-01-01

61

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

PubMed Central

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?accurate and real-time 3D tumor localization on current standard LINACs with a single x-ray imager.

Li, Ruijiang; Fahimian, Benjamin P.; Xing, Lei

2011-01-01

62

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

PubMed

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. 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 the target point and delivery isocenter) and cone alignment (isocenter precision under gantry rotation) were measured using the optical-CT images. 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 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. 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

2013-11-01

63

Comparative analysis of the methods of drug and protein delivery for the treatment of cancer, genetic diseases and diagnostics.  

PubMed

The methods of protein and drug delivery for the treatment of cancer, genetic diseases and diagnostics were summarized. The potential of protein transduction is discussed and the recent developments in the field are reviewed. An overview is provided of the non-viral delivery methods such as liposomes, polymer-based delivery, cell-penetrating peptides, bacterial secretion, cells, virosomes, physical methods including electroporation, microinjection, osmotic lysis, nanoparticles, sonoporation to locally inject therapeutic molecules. The characteristic properties of non-viral vectors and their use for the delivery of therapeutic molecules for the diagnosis and treatment of disorders and to target tumors are also discussed. The potential of the transduced peptides and proteins was used as new therapeutic compounds against infectious diseases, to complement deficiencies in specific genes, to specifically kill tumour cells, for gene therapy. The protein delivery vectors can enhance the transfection at low concentrations and help to develop future gene delivery systems with reduced toxicity. Vitamin B12, folic acid, biotin, and riboflavin are essential in the treatment of cancer. Ultrasound has a potential in the delivery of therapeutic agents. The new developing technologies of drug delivery and targeting offer the possibility to improve the therapeutic possibilities of the existing drugs and to develop novel therapeutics. PMID:21864112

Todorova, Roumiana

2011-11-01

64

Disposable Device for Delivery of Accurate and Filtered Liquid Samples (Continuation of Patent Application Serial No. 7-844 057, Filed March 2, 1992).  

National Technical Information Service (NTIS)

The invention concerns in general a method and apparatus for providing an accurate and filtered sample using a positive displacement pipet operated in combination with a disposable cylindrical tube and piston and followed by a disposable syringe filter wh...

A. P. Murphy M. K. Price

1993-01-01

65

Method of Delivery of Accurate and Filtered Liquid Samples (Continuation of Patent Application Serial No. 7-844 057, Filed March 2, 1992).  

National Technical Information Service (NTIS)

The invention concerns in general a method and apparatus for providing an accurate and filtered sample using a positive displacement pipet operated in combination with a disposable cylindrical tube and piston and followed by a disposable syringe filter wh...

A. P. Murphy M. K. Price

1993-01-01

66

Adolescent Substance-use Treatment: Service Delivery, Research on Effectiveness, and Emerging Treatment Alternatives  

Microsoft Academic Search

Adolescent substance use remains a persistent and serious problem in society despite use patterns showing consistent declines in alcohol and other illicit drug use since 2000. This paper provides an overview of the somewhat confusing landscape of substance-use treatment options available to families and professionals seeking treatment services. A case study is presented illustrating one treatment option, termed outdoor behavioral

Keith C. Russell

2008-01-01

67

Use of Liposomes as Drug Delivery Vehicles for Treatment of Melanoma  

PubMed Central

Melanoma is a progressive disease that claims many lives each year due to lack of therapeutics effective for the long-term treatment of patients. Currently, the best treatment option is early detection followed by surgical removal. Better melanoma therapies that are effectively delivered to tumors with minimal toxicity for patients are urgently needed. Nanotechnologies provide one approach to encapsulate therapeutic agents leading to improvements in circulation time, enhanced tumor uptake, avoidance of the reticulo-endothelial system, and minimization of toxicity. Liposomes in particular are a promising nanotechnology that can be used for more effective delivery of therapeutic agents to treat melanoma. Liposomes delivering chemotherapies, siRNA, asODNs, DNA, and radioactive particles are just some of the promising new nanotechnology based therapies under development for the treatment of melanoma that are discussed in this review.

Tran, Melissa A.; Watts, Rebecca J.; Robertson, Gavin P.

2009-01-01

68

Polymer-Based Delivery of Glucagon-Like Peptide-1 for the Treatment of Diabetes  

PubMed Central

The incretin hormones, glucagon-like peptide-1 (GLP-1) and its receptor agonist (exendin-4), are well known for glucose homeostasis, insulinotropic effect, and effects on weight loss and food intake. However, due to the rapid degradation of GLP-1 by dipeptidylpeptidase-IV (DPP-IV) enzyme and renal elimination of exendin-4, their clinical applications have been restricted. Although exendin-4 has longer half-life than GLP-1, it still requires frequent injections to maintain efficacy for the treatment of diabetes. In recent decades, various polymeric delivery systems have been developed for the delivery of GLP-1 and exendin-4 genes or peptides for their long-term action and the extra production in ectopic tissues. Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides. In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described. Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed.

Kim, Pyung-Hwan; Kim, Sung Wan

2012-01-01

69

Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs  

PubMed Central

Controlled-release delivery of 6-?-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. Microneedle pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6 fold enhancement in steady state plasma concentration was observed in vivo with MN treated skin with NTXOL·HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible non-lipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application.

Banks, Stan L.; Pinninti, Raghotham R.; Gill, Harvinder S.; Paudel, Kalpana S.; Crooks, Peter A.; Brogden, Nicole K.; Prausnitz, Mark R.; Stinchcomb, Audra L.

2010-01-01

70

Novel magnetic/ultrasound focusing system enhances nanoparticle drug delivery for glioma treatment  

PubMed Central

Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood–brain barrier penetration. Here, we combine 2 methods to increase drug delivery to brain tumors. Focused ultrasound transiently permeabilizes the blood–brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring.

Chen, Pin-Yuan; Liu, Hao-Li; Hua, Mu-Yi; Yang, Hung-Wei; Huang, Chiung-Yin; Chu, Po-Chun; Lyu, Lee-Ang; Tseng, I-Chou; Feng, Li-Ying; Tsai, Hong-Chieh; Chen, Shu-Mei; Lu, Yu-Jen; Wang, Jiun-Jie; Yen, Tzu-Chen; Ma, Yunn-Hwa; Wu, Tony; Chen, Jyh-Ping; Chuang, Jih-Ing; Shin, Jyh-Wei; Hsueh, Chuen; Wei, Kuo-Chen

2010-01-01

71

Polymer-based delivery of glucagon-like Peptide-1 for the treatment of diabetes.  

PubMed

The incretin hormones, glucagon-like peptide-1 (GLP-1) and its receptor agonist (exendin-4), are well known for glucose homeostasis, insulinotropic effect, and effects on weight loss and food intake. However, due to the rapid degradation of GLP-1 by dipeptidylpeptidase-IV (DPP-IV) enzyme and renal elimination of exendin-4, their clinical applications have been restricted. Although exendin-4 has longer half-life than GLP-1, it still requires frequent injections to maintain efficacy for the treatment of diabetes. In recent decades, various polymeric delivery systems have been developed for the delivery of GLP-1 and exendin-4 genes or peptides for their long-term action and the extra production in ectopic tissues. Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides. In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described. Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed. PMID:22701182

Kim, Pyung-Hwan; Kim, Sung Wan

2012-01-01

72

Drug and cell encapsulation: alternative delivery options for the treatment of malignant brain tumors.  

PubMed

Malignant brain tumors including glioblastoma are incurable cancers. Over the last years a number of promising novel treatment approaches have been investigated including the application of inhibitors of receptor tyrosine kinases and downstream targets, immune-based therapies and anti-angiogenic agents. Unfortunately so far the major clinical trials in glioblastoma patients did not deliver clear clinical benefits. Systemic brain tumor therapy is seriously hampered by poor drug delivery to the brain. Although in glioblastoma, the blood brain barrier is disrupted in the tumor core, the major part of the tumor is largely protected by an intact blood brain barrier. Active cytotoxic compounds encapsulated into liposomes, micelles, and nanoparticles constitute novel treatment options because they can be designed to facilitate entry into the brain parenchyma. In the case of biological therapeutics, encapsulation of therapeutic cells and their implantation into the surgical cavity represents another promising approach. This technology provides long term release of the active compound at the tumor site and reduces side effects associated with systemic delivery. The proof of principle of encapsulated cell factories has been successfully demonstrated in experimental animal models and should pave the way for clinical application. Here we review the challenges associated with the treatment of brain tumors and the different encapsulation options available for drugs and living cells, with an emphasis on alginate based cell encapsulation technology. PMID:24491927

Bhujbal, Swapnil V; de Vos, Paul; Niclou, Simone P

2014-04-01

73

Expectant management of severe preeclampsia remote from term: patient selection, treatment, and delivery indications.  

PubMed

Severe preeclampsia that develops at <34 weeks of gestation is associated with high perinatal mortality and morbidity rates. Management with immediate delivery leads to high neonatal mortality and morbidity rates and prolonged hospitalization in the neonatal intensive care unit because of prematurity. Conversely, attempts to prolong pregnancy with expectant management may result in fetal death or asphyxial damage in utero and increased maternal morbidity. Since 1990, 2 randomized trials and several observational studies have evaluated the benefits vs risks of expectant management of severe preeclampsia at <34 weeks of gestation. These studies included 1677 women with gestational age between 24 and 34 weeks and 115 women with gestational age of <25 weeks (overlap in some studies). The results of these studies suggest that expectant treatment in a select group of women with severe preeclampsia between 24 0/7 and 32 6/7 weeks of gestation in a suitable hospital is safe and improves neonatal outcome. For gestational age of <24 0/7 weeks, expectant treatment was associated with high maternal morbidity with limited perinatal benefit. Based on the review of these studies and our own experience, recommendations are made for the selection of the appropriate candidates for expectant treatment, criteria for maternal-fetal monitoring, and targets for delivery. Finally, we provide information regarding maternal counseling based on maternal condition and fetal gestational age at time of diagnosis. PMID:17547875

Sibai, Baha M; Barton, John R

2007-06-01

74

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

75

Cell penetrating peptide delivery of splice directing oligonucleotides as a treatment for Duchenne muscular dystrophy.  

PubMed

Duchenne muscular dystrophy is a severe, X-linked muscle wasting disorder caused by the absence of an integral structural protein called dystrophin. This is caused by mutations or deletions in the dystrophin gene which disrupt the reading frame, thereby halting the production of a functional protein. A number of potential therapies have been investigated for the treatment of this disease including utrophin upregulation, 'stop-codon read through' aminoglycosides and adeno-associated virus gene replacement as well as stem cell therapy. However, the most promising treatment to date is the use of antisense oligonucleotides which cause exon skipping by binding to a specific mRNA sequence, skipping the desired exon, thereby restoring the reading frame and producing a truncated yet functional protein. The results from recent 2'OMePS and morpholino clinical trials have renewed hope for Duchenne patients; however in vivo studies in a mouse model, mdx, have revealed low systemic distribution and poor delivery of oligonucleotides to affected tissues such as the brain and heart. However a variety of cell penetrating peptides directly conjugated to antisense oligonucleotides have been shown to enhance delivery in Duchenne model systems with improved systemic distribution and greater efficacy compared to 'naked' antisense oligonucleotides. These cell penetrating peptides, combined with an optimised dose and dosing regimen, as well as thorough toxicity profile have the potential to be developed into a promising treatment which may be progressed to clinical trial. PMID:23140454

Betts, Corinne A; Wood, Matthew J A

2013-01-01

76

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

77

Treatment Planning to Improve Delivery Accuracy and Patient Throughput in Helical Tomotherapy  

SciTech Connect

Purpose: To investigate delivery quality assurance (DQA) discrepancies observed for a subset of helical tomotherapy patients. Methods and Materials: Six tomotherapy patient plans were selected for analysis. Three had passing DQA ion chamber (IC) measurements, whereas 3 had measurements deviating from the expected dose by more than 3.0%. All plans used similar parameters, including: 2.5 cm field-width, 15-s gantry period, and pitch values ranging from 0.143 to 0.215. Preliminary analysis suggested discrepancies were associated with plans having predominantly small leaf open times (LOTs). To test this, patients with failing DQA measurements were replanned using an increased pitch of 0.287. New DQA plans were generated and IC measurements performed. Exit fluence data were also collected during DQA delivery for dose reconstruction purposes. Results: Sinogram analysis showed increases in mean LOTs ranging from 29.8% to 83.1% for the increased pitch replans. IC measurements for these plans showed a reduction in dose discrepancies, bringing all measurements within {+-}3.0%. The replans were also more efficient to deliver, resulting in reduced treatment times. Dose reconstruction results were in excellent agreement with IC measurements, illustrating the impact of leaf-timing inaccuracies on plans having predominantly small LOTs. Conclusions: The impact of leaf-timing inaccuracies on plans with small mean LOTs can be considerable. These inaccuracies result from deviations in multileaf collimator latency from the linear approximation used by the treatment planning system and can be important for plans having a 15-s gantry period. The ability to reduce this effect while improving delivery efficiency by increasing the pitch is demonstrated.

Westerly, David C. [Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States)], E-mail: westerly@wisc.edu; Soisson, Emilie [Department of Human Oncology, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Chen Quan [Department of TomoTherapy, Inc., Madison, WI (United States); Woch, Katherine [Department of Human Oncology, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Schubert, Leah [Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Olivera, Gustavo [Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Department of TomoTherapy, Inc., Madison, WI (United States); Mackie, Thomas R. [Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Department of Human Oncology, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Department of TomoTherapy, Inc., Madison, WI (United States)

2009-07-15

78

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

79

Assessing Fidelity of Treatment Delivery in Group and Individual 12-Step Facilitation  

PubMed Central

Twelve Step Facilitation (TSF) is an emerging, empirically supported treatment, the study of which will be strengthened by rigorous fidelity assessment. This report describes the development, reliability and concurrent validity of the Twelve Step Facilitation Adherence Competence Empathy Scale (TSF ACES), a comprehensive fidelity rating scale for group and individual TSF treatment developed for the National Drug Abuse Treatment Clinical Trials Network study, Stimulant Abuser Groups to Engage in 12-Step. Independent raters used TSF ACES to rate treatment delivery fidelity of 966 (97% of total) TSF group and individual sessions. TSF ACES summary measures assessed therapist treatment adherence, competence, proscribed behaviors, empathy and overall session performance. TSF ACES showed fair to good overall reliability; weighted kappa coefficients for 59 co-rated sessions ranged from .31–1.00, with a mean of .69. Reliability ratings for session summary measures were good to excellent (.69–.91). Internal consistency for the instrument was variable (.47–.71). Relationships of the TSF ACES summary measures with each other, as well as relationships of the summary measures with a measure of therapeutic alliance provided support for concurrent and convergent validity. Implications and future directions for use of TSF ACES in clinical trials and community treatment implementation are discussed.

Campbell, Barbara K.; Manuel, Jennifer K.; Manser, Sarah Turcotte; Peavy, K. Michelle; Stelmokas, Julija; McCarty, Dennis; Guydish, Joseph R.

2012-01-01

80

Risk Factors for Uterine Atony/Postpartum Hemorrhage Requiring Treatment after Vaginal Delivery  

PubMed Central

Objective To identify risk factors for uterine atony or hemorrhage. Study Design Secondary analysis of a 3-arm double-blind randomized trial of different dose-regimens of oxytocin to prevent uterine atony after vaginal delivery. The primary outcome was uterine atony or hemorrhage requiring treatment. Twenty-one potential risk factors were evaluated. Logistic regression was used to identify independent risk factors using 2 complementary pre-defined model selection strategies. Results Among 1798 women randomized to 10, 40 or 80U prophylactic oxytocin after vaginal delivery, treated uterine atony occurred in 7%. Hispanic (OR 2.1; 95% CI 1.3–3.4) and non-Hispanic whites (OR 1.6; 95% CI 1.0–2.5), preeclampsia (OR 3.2; 95% CI 2.0–4.9) and chorioamnionitis (OR 2.8; 95% CI 1.6–5.0) were consistent independent risk factors. Other risk factors based on the specified selection strategies were obesity, induction/augmentation of labor, twins, hydramnios, anemia, and arrest of descent. Amnioinfusion appeared to be protective against uterine atony (OR 0.53; 95% CI 0.29–0.98). Conclusion Independent risk factors for uterine atony requiring treatment include Hispanic and non-Hispanic white ethnicity, preeclampsia and chorioamnionitis.

Wetta, Luisa A; Szychowski, Jeff M; Seals, Ms. Samantha; Mancuso, Melissa S; Biggio, Joseph R; Tita, Alan TN

2013-01-01

81

Liposomal delivery and polyethylene glycol-liposomal oxaliplatin for the treatment of colorectal cancer (Review)  

PubMed Central

Oxaliplatin is effective for the treatment of advanced colorectal cancer; however, its application is restricted due to its dose-limiting toxicity. Liposomes are sphere-shaped vesicles consisting of one or more phospholipid bilayers. Liposomes as drug carriers are characterized by delayed release, lesion targeting and may be used as a drug-delivery system to decrease the side effects of cytotoxic drugs. Active targeting modification of liposomes may change the biological distribution of the anticancer agents, reduce or reverse multidrug resistance of tumor cells and enhance the effects of anticancer therapy. Based on the characteristics mentioned above, the aim of the present review was to demonstrate that polyethylene glycol-liposomes containing oxaliplatin may offer advantages for the treatment of colorectal cancer in clinical practice.

YANG, CHUANG; FU, ZHONG-XUE

2014-01-01

82

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

83

Proton radiotherapy for chest wall and regional lymphatic radiation; dose comparisons and treatment delivery  

PubMed Central

Purpose The delivery of post-mastectomy radiation therapy (PMRT) can be challenging for patients with left sided breast cancer that have undergone mastectomy. This study investigates the use of protons for PMRT in selected patients with unfavorable cardiac anatomy. We also report the first clinical application of protons for these patients. Methods and materials Eleven patients were planned with protons, partially wide tangent photon fields (PWTF), and photon/electron (P/E) fields. Plans were generated with the goal of achieving 95% coverage of target volumes while maximally sparing cardiac and pulmonary structures. In addition, we report on two patients with unfavorable cardiac anatomy and IMN involvement that were treated with a mix of proton and standard radiation. Results PWTF, P/E, and proton plans were generated and compared. Reasonable target volume coverage was achieved with PWTF and P/E fields, but proton therapy achieved superior coverage with a more homogeneous plan. Substantial cardiac and pulmonary sparing was achieved with proton therapy as compared to PWTF and P/E. In the two clinical cases, the delivery of proton radiation with a 7.2 to 9 Gy photon and electron component was feasible and well tolerated. Akimbo positioning was necessary for gantry clearance for one patient; the other was treated on a breast board with standard positioning (arms above her head). LAO field arrangement was used for both patients. Erythema and fatigue were the only noted side effects. Conclusions Proton RT enables delivery of radiation to the chest wall and regional lymphatics, including the IMN, without compromise of coverage and with improved sparing of surrounding normal structures. This treatment is feasible, however, optimal patient set up may vary and field size is limited without multiple fields/matching.

2013-01-01

84

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

85

Transient antiangiogenic treatment improves delivery of cytotoxic compounds and therapeutic outcome in lung cancer.  

PubMed

Extensive oncologic experience argues that the most efficacious applications of antiangiogenic agents rely upon a combination with cytotoxic drugs. Yet there remains a lack of clarity about how to optimize scheduling for such drug combinations. Prudent antiangiogenic therapy might transiently normalize blood vessels to improve tumor oxygenation and drug exposure. Using [(15)O]H2O positron emission tomography imaging in a preclinical mouse model of non-small cell lung cancer, we observed that short-term treatment with the vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibitor PTK787 licensed a transient window of improved tumor blood flow. The improvement observed was associated with a reduced leakiness from tumor vessels, consistent with induction of a vascular normalization process. Initiation of a cytotoxic treatment in this window of tumor vessel normalization resulted in increased efficacy, as illustrated by improved outcomes of erlotinib administration after initial PTK787 treatment. Notably, intermittent PTK787 treatment also facilitated long-term tumor regression. In summary, our findings offer strong evidence that short-term antiangiogenic therapy can promote a transient vessel normalization process that improves the delivery and efficacy of a targeted cytotoxic drug. Cancer Res; 74(10); 2816-24. ©2014 AACR. PMID:24675359

Chatterjee, Sampurna; Wieczorek, Caroline; Schöttle, Jakob; Siobal, Maike; Hinze, Yvonne; Franz, Thomas; Florin, Alexandra; Adamczak, Joanna; Heukamp, Lukas C; Neumaier, Bernd; Ullrich, Roland T

2014-05-15

86

Convection-enhanced delivery of nanocarriers for the treatment of brain tumors.  

PubMed

Primary brain tumors have a significant infiltrative capacity as their reappearance after resection usually occurs within 2cm of the tumor margin. Local delivery method such as Convection-Enhanced Delivery (CED) has been introduced to avoid this recurrence by delivering active molecules via positive-pressure methods. For an efficient infusion, the distribution volume of the drug has to be optimized while avoiding backflow, since this is responsible for side effects and a reduction of therapeutic efficacy. The encapsulation of the drug infused in nanosized structures can be considered, which would lead to a reduction of both toxicity of the treatment and infusion time during CED. In the present review, we will firstly discuss the technical approach of CED with regard to catheter design and brain characteristics; secondly, we will describe the 'ideal' nanocarrier in terms of size, surface properties, and interaction with the extracellular matrix for optimal diffusion in the brain parenchyma. We also discuss preclinical and clinical applications of this new method. PMID:19168213

Allard, Emilie; Passirani, Catherine; Benoit, Jean-Pierre

2009-04-01

87

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 384h 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

88

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

2007-06-01

89

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.

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

2012-01-01

90

Alzheimer’s disease treatment: Assessing caregiver preferences for mode of treatment delivery  

Microsoft Academic Search

Introduction  Management of patients with Alzheimer’s Disease (AD) can exert a substantial burden upon caregivers. As new modes of treatment\\u000a administration are developed, it is important to assess caregiver satisfaction and preference in a standardized manner. This\\u000a study describes the development of the Alzheimer’s Disease Caregiver Preference Questionnaire (ADCPQ) to assess AD caregivers’\\u000a satisfaction with and preference for patch or capsule

Linda Abetz; Diana Rofail; Polyxane Mertzanis; Rebecca Heelis; Kathleen Rosa; Crystal Tellefsen; Aude Roborel de Climens; Christopher McBurney; Simu Thomas

2009-01-01

91

Treatments of pelvic girdle pain in pregnant women: adverse effects of standard treatment, acupuncture and stabilising exercises on the pregnancy, mother, delivery and the fetus\\/neonate  

Microsoft Academic Search

BACKGROUND: Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain, PGP, in pregnant women. However, the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition. The aim of the present work was to assess adverse effects of acupuncture on the pregnancy, mother, delivery

Helen Elden; Hans-Christian Ostgaard; Monika Fagevik-Olsen; Lars Ladfors; Henrik Hagberg

2008-01-01

92

TREATMENT Validation of a Scale for Rating the Delivery of PsychoSocial Treatments for Alcohol Dependence and Misuse: The UKATT Process Rating Scale (PRS)  

Microsoft Academic Search

Aim: The aim of this study was to describe the development and validation of the UK Alcohol Treatment Trial Process Rating Scale (UKATT PRS), a manual based method for monitoring and rating the delivery of psychosocial treatments of alcohol dependence and misuse. Methods: Following adaptation and further development of a validated rating scale, the ability of the UKATT PRS to

Gillian Tober; Wendy Clyne; Olwyn Finnegan; Amanda Farrin; Ian Russell

93

Discuss the impact technological advances in equipment and materials have made on the delivery and outcome of endodontic treatment.  

PubMed

Recent advances in endodontic equipment and materials have considerably changed the manner in which endodontic treatment is delivered. Specific technological advances, including nickel-titanium instruments, ultrasonic instruments and the dental operating microscope have been associated with increased efficiency and efficacy of treatment and simplification of delivery. The effects of most of these changes have been tested via in vitro studies and case reports. Ongoing studies should constantly investigate what effects technological advances might have on the outcome of endodontic treatment. PMID:24118265

Lababidi, Emad Aldin

2013-12-01

94

Evaluation of Intracavitary Chemotherapy Delivery for the Treatment of Mammary Carcinoma.  

National Technical Information Service (NTIS)

This project will evaluate paclitaxel chemotherapy delivery from a gel polymer system placed into a wound bed following conservative (marginal) surgical removal of human breast cancers grown in nude mice. This delivery method is proposed to control local ...

W. S. Dernell

2004-01-01

95

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

96

Treatment of Parturition-Induced Rupture of Pubic Symphysis after Spontaneous Vaginal Delivery  

PubMed Central

Parturition-induced rupture of pubic symphysis is an uncommon but severe complication of delivery. Characteristic symptoms are an immediate onset of suprapubic and/or sacroiliac pain within the first 24 hours postpartum, often accompanied by an audible crack. Diagnosis can be confirmed by imaging including X-ray, Magnet Resonance Imaging (MRI), and ultrasound. However, there is no consensus on the optimal therapy. Conservative treatment is predominantly used. It has been reported that, in cases of extreme symphyseal rupture with pelvic instability or persisting pain after conservative therapy, operative treatment achieves a successful outcome. In this report, we present a case of a twenty-year-old primigravida who developed suprapubic pain after a nonoperative vaginal birth with shoulder dystocia. A rupture of pubic symphysis with a gap of 60?mm was confirmed by means of X-ray and MRI. Simultaneously, other pelvic joint injuries could be excluded. Operative treatment by an open reduction and internal plate fixation yielded excellent results.

Graf, C.; Sellei, R. M.; Schrading, S.; Bauerschlag, D. O.

2014-01-01

97

Efficient and accurate treatment of weak pairs in local CCSD(T) calculations. II. Beyond the ring approximation.  

PubMed

In order to arrive at linear scaling of the computational cost with molecular size, local coupled cluster methods discriminate pairs of local molecular orbitals according to the spatial separation R of the latter. Only strong pairs are treated at the full coupled cluster level, whereas for weak pairs a lower level of theory (usually Møller-Plesset perturbation theory of second order, MP2) is used. Yet an MP2 treatment of weak pairs is inadequate in certain situations (for example, for describing ?-stacking), which calls for an improved but still inexpensive method for dealing with the weak pairs. In a previous contribution, we proposed as a substituent for MP2 the LrCCD3 method, which is based on ring coupled cluster doubles (ring-CCD) and includes all third-order diagrams with energy contributions decaying not quicker than R(-6). In the present work, we explore a still more accurate method, which is based on the same principles. It turned out to be essential to abandon the restriction to ring-CCD, i.e., to include further CCD diagrams beyond the ring approximation. The occurring intermediates turn out to be formally very similar to LMP2 density matrices, such that an efficient evaluation of these non-ring CCD diagrams is possible. Furthermore, a computationally cheap a posteriori estimate for the fourth-order singles contribution to the weak pair energy, which also exhibits a decay behavior of R(-6), is introduced. The resulting method, denoted as LCCD[S]-R(-6), indeed provides a substantial improvement in accuracy over the previous LrCCD3 method at a relatively modest additional computational cost. PMID:24985618

Schütz, Martin; Masur, Oliver; Usvyat, Denis

2014-06-28

98

Long term impact of large scale community-directed delivery of doxycycline for the treatment of onchocerciasis  

PubMed Central

Background Anti-Wolbachia treatment with doxycycline is effective in sterilising and killing adult Onchocerca volvulus nematodes, proving superior to ivermectin and of great potential as an alternative approach for the treatment and control of onchocerciasis, particularly in areas of Loa loa co-endemicity. Nevertheless, the length of the required treatment poses potential logistical problems and risk of poor compliance, raising a barrier to the use of doxycycline in Mass Drug Administration (MDA) strategies. In 2007 and 2008 a feasibility trial of community-directed treatment with doxycycline was carried out in two health districts in Cameroon, co-endemic for O. volvulus and L. loa. With 17,519 eligible subjects, the therapeutic coverage was 73.8% with 97.5% compliance, encouraging the feasibility of using doxycycline community-directed delivery in restricted populations of this size. The current study evaluated the effectiveness of this community-directed delivery of doxycycline four years after delivery. Findings Infection with O. volvulus was evaluated by skin biopsy and nodule palpation. Of the 507 subjects recruited, 375 had completed the treatment with doxycycline followed by one or two rounds of annual ivermectin MDA and 132 received one or two rounds of annual ivermectin MDA alone. Statistically significant lower microfilarial prevalence (17.0% [doxycycline plus ivermectin group], 27.0% [ivermectin only group], p = 0.014) and load (p = 0.012) were found in people that had received doxycycline followed by ivermectin compared to those who received ivermectin only. Conclusions This study demonstrates the long-term effectiveness of doxycycline treatment delivered with a community-directed strategy even when evaluated four years after delivery in an area of ongoing transmission. This finding shows that a multi-week course of treatment is not a barrier to community-delivery of MDA in restricted populations of this size and supports its implementation to compliment existing control strategies for onchocerciasis, where needed.

2012-01-01

99

Constant dopaminergic stimulation by transdermal delivery of dopaminergic drugs: a new treatment paradigm in Parkinson's disease.  

PubMed

Current dopaminergic therapies for the treatment of Parkinson's disease are associated with the development of long-term motor complications. Abnormal pulsatile stimulation of dopamine receptors is thought to underlie the development of motor complications. There is thus a need for therapies that mimic the normal physiological state more closely by resulting in constant dopaminergic stimulation (CDS). Several studies support the hypothesis that CDS can reverse levodopa-induced motor complications. Other potential benefits of CDS include alleviating nocturnal disturbances, minimizing daytime sleepiness, avoiding priming for motor fluctuations and dyskinesia, preventing the development of gastrointestinal dysfunction and reducing the risk of developing psychosis or behavioural disturbances. Continuous infusion of dopaminergic therapies is impractical for the routine treatment of large numbers of patients. Although catechol-O-methyltransferase inhibitors or sustained-release preparations of levodopa may be beneficial, they do not entirely eliminate pulsatile stimulation of dopamine receptors. A new dopamine agonist (rotigotine), delivered over 24 h by a once-daily transdermal patch, has been investigated in several clinical trials. Continuous delivery of rotigotine has been shown to provide 'true' CDS in animal models. The potential of true CDS therapy to prevent or reduce long-term motor and non-motor complications requires investigation in appropriately designed clinical trials. PMID:18042245

Steiger, M

2008-01-01

100

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

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.

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.

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

Targeted liposomal drug delivery systems for the treatment of B cell malignancies.  

PubMed

Abstract Nanoparticulate systems have demonstrated significant potential for overcoming the limitations of non-specific adverse effects related to chemotherapy. The treatment of blood malignancies employing targeted particulate drug delivery systems presents unique challenges and considerable research has been focused towards the development of targeted liposomal formulations for B cell malignancies. These formulations are aimed at achieving selectivity towards the malignant cells by targeting several cell surface markers which are over-expressed in that specific malignancy. CD19, CD20, CD22 and CD74 are few of such markers of which CD19, CD22 and CD74 are internalizing and CD20 is non-internalizing. Systems which have been developed to target both types of these cell surface markers are discussed. Specifically, the efficacy and development of targeted liposomes is considered. A number of studies have demonstrated the advantages of targeted liposomal systems encapsulating doxorubicin or vincristine. However, liposomal encapsulation of newer anti-neoplastic agents such as AD 198 which are superior to doxorubicin should be considered. PMID:24433007

Mittal, Nivesh K; Bhattacharjee, Himanshu; Mandal, Bivash; Balabathula, Pavan; Thoma, Laura A; Wood, George C

2014-06-01

104

Solid lipid nanoparticles for potential Doxorubicin delivery in glioblastoma treatment: preliminary in vitro studies.  

PubMed

The major obstacle to glioblastoma pharmacological therapy is the overcoming of the blood-brain barrier (BBB). In literature, several strategies have been proposed to overcome the BBB: in this experimental work, solid lipid nanoparticles (SLN), prepared according to fatty acid coacervation technique, are proposed as the vehicle for doxorubicin (Dox), to enhance its permeation through an artificial model of BBB. The in vitro cytotoxicity of Dox-loaded SLN has been measured on three different commercial and patient-derived glioma cell lines. Dox was entrapped within SLN thanks to hydrophobic ion pairing with negatively charged surfactants, used as counterions. Results indicate that Dox entrapped in SLN maintains its cytotoxic activity toward glioma cell lines; moreover, its permeation through hCMEC/D3 cell monolayer, assumed as a model of the BBB, was increased when the drug was entrapped in SLN. In conclusion, SLN proved to be a promising vehicle for the delivery of Dox to the brain in glioblastoma treatment. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2157-2165, 2014. PMID:24824141

Battaglia, Luigi; Gallarate, Marina; Peira, Elena; Chirio, Daniela; Muntoni, Elisabetta; Biasibetti, Elena; Capucchio, Maria Teresa; Valazza, Alberto; Panciani, Pier Paolo; Lanotte, Michele; Schiffer, Davide; Annovazzi, Laura; Caldera, Valentina; Mellai, Marta; Riganti, Chiara

2014-07-01

105

Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain  

PubMed Central

Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder.

Goins, WF; Goss, JR; Chancellor, MB; de Groat, WC; Glorioso, JC; Yoshimura, N

2009-01-01

106

Treatments of pelvic girdle pain in pregnant women: adverse effects of standard treatment, acupuncture and stabilising exercises on the pregnancy, mother, delivery and the fetus/neonate  

PubMed Central

Background Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain, PGP, in pregnant women. However, the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition. The aim of the present work was to assess adverse effects of acupuncture on the pregnancy, mother, delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to standard treatment or standard treatment alone. Methods In all, 386 women with PGP entered this controlled, single-blind trial. They were randomly assigned to standard treatment plus acupuncture (n = 125), standard treatment plus specific stabilising exercises (n = 131) or to standard treatment alone (n = 130) for 6 weeks. Acupuncture that may be considered strong was used and treatment was started as early as in the second trimester of pregnancy. Adverse effects were recorded during treatment and throughout the pregnancy. Influence on the fetus was measured with cardiotocography (CTG) before-during and after 43 acupuncture sessions in 43 women. A standardised computerized method to analyze the CTG reading numerically (Oxford 8000, Oxford, England) was used. After treatment, the women rated their overall experience of the treatment and listed adverse events if any in a questionnaire. Data of analgesia and oxytocin augmentation during labour, duration of labour, frequency of preterm birth, operative delivery, Apgar score, cord-blood gas/acid base balance and birth weight were also recorded. Results There were no serious adverse events after any of the treatments. Minor adverse events were common in the acupuncture group but women rated acupuncture favourably even despite this. The computerized or visually assessed CTG analyses of antenatal recordings in connection with acupuncture were all normal. Conclusion This study shows that acupuncture administered with a stimulation that may be considered strong led to minor adverse complaints from the mothers but had no observable severe adverse influences on the pregnancy, mother, delivery or the fetus/neonate.

Elden, Helen; Ostgaard, Hans-Christian; Fagevik-Olsen, Monika; Ladfors, Lars; Hagberg, Henrik

2008-01-01

107

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

108

Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases.  

PubMed

The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. Mucoadhesive micromatricial chitosan/poly(epsilon-caprolactone) (CH/PCL) films and chitosan films were prepared. Thermal behavior, morphology, and particle size measurements were used to evaluate the prepared films. The effect of different molar masses of CH and different ratios of medium Mwt molar mass chitosan (MCH):PCL on water absorption, in vitro bioadhesion, mechanical properties, and in vitro drug release was examined. In vivo performance of the selected formulation was also evaluated. Differential scanning calorimetry examination revealed that MET existed mainly in amorphous form. Under microscopic examination, PCL microparticles were homogeneously dispersed in the films. The use of different molar masses of CH and different ratios of (MCH):PCL affected the size of the entrapped particles. Addition of PCL significantly decreased percentage water uptake and bioadhesion force compared with pure CH film. With regard to mechanical properties, the 2-layered film containing 1:0.625 MCH:PCL had the best tensile properties. At fixed CH:PCL ratio (1:1.25), the slowest drug release was obtained from films containing high molar mass CH. On the other hand, the 2-layered film that consisted of 1:0.625 MCH:PCL had the slowest MET release. In vivo evaluation of the selected film revealed that metronidazole concentration in saliva over 6 hours ranged from 5 to 15 microg/mL, which was within and higher than the reported range of minimum inhibitory concentration for metronidazole. A significant in vitro/in vivo correlation under the adopted experimental conditions was obtained. PMID:17915825

El-Kamel, Amal Hassan; Ashri, Lubna Y; Alsarra, Ibrahim A

2007-01-01

109

Formulation and characterization of atovaquone nanosuspension for improved oral delivery in the treatment of malaria.  

PubMed

Aim: The objective of the present study was to develop an atovaquone (ATQ) nanosuspension and evaluate its ability to improve the pharmacokinetic and therapeutic efficacy on oral administration. Materials & methods: The ATQ nanosuspension was prepared by a combination of microprecipitation and high-pressure homogenization. It was freeze dried and characterized for various physiochemical properties. In vivo pharmacokinetics was performed in rats whereas antimalarial efficacy was assessed in mice using a 4-day suppressive test. Results: The ATQ nanosuspension stabilized with Solutol(®) HS 15 (BASF India Ltd, Mumbai, India) and Capryol™ 90 (Gattefosse, Mumbai, India) exhibited a z-average diameter of 371.50 nm and a polydispersity index of 0.19. X-ray diffraction and differential scanning calorimetry analysis indicated no substantial changes in the crystalline state of ATQ nanocrystals. The aqueous solubility and in vitro dissolution rate were significantly increased by reducing the particle size. An in vivo pharmacokinetics study of the nanosuspension compared with a drug suspension and Malarone(®) (GlaxoSmithKline, Brentford, UK) exhibited an approximately 4.6-3.2-fold improvement in area under plasma concentration. A significant increase in Cmax and decrease in time to reach peak plasma concentration after administration was also observed. ATQ in nanosized form, even at one-quarter lower doses, exhibited greater reduction in parasitemia and prolonged survival compared with its reference formulations. Conclusion: Results of this pilot study highlight the potential of nanosuspension as an efficient and commercially viable strategy for improving delivery of ATQ for malaria treatment. Original submitted 1 August 2011; Revised submitted 2 February 2013. PMID:23927590

Borhade, Vivek; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

2014-04-01

110

Sustained-release delivery systems of triclosan for treatment of Streptococcus mutans biofilm.  

PubMed

Dental diseases are chronic infections caused by oral bacteria harboring the dental biofilm. Local sustained-release delivery systems prolong the duration of a drug in the oral cavity, thus enhancing its therapeutic potential, while reducing its side effects. Triclosan is an agent that was found to have an antibacterial effect against oral bacteria. However, its substantivity in the oral cavity is low, resulting in reduced antibacterial efficiency. The purpose of this study was to develop a local sustained release device containing triclosan and to test its antibacterial efficacy on Streptococcus mutans biofilm. Our results show that we can formulate an ethylcellulose-based, nondegradable, sustained-release device in which 80% of the loaded triclosan is released over a 10-day period. The release rate of triclosan corresponded to the Higuchi's planar homogenous diffusion release model (r2 = 0.998). A degradable local sustained-release delivery based on a methacrylate ester matrix was also developed for a faster release rate of triclosan. The release kinetics in those types of sustained-release delivery systems was erosion control. The local sustained-release delivery system significantly affected the viability of S. mutans in biofilm compared to placebo as was tested by confocal laser scanning microscopy. Our in vitro results show that triclosan can be incorporated into degradable or nondegradable sustained-release drug delivery systems. The release of triclosan from the local sustained-release delivery system can be controlled, thus extending its antibacterial properties. PMID:16362957

Steinberg, Doron; Tal, Tamir; Friedman, Michael

2006-05-01

111

Nanodrug delivery systems: a promising technology for detection, diagnosis, and treatment of cancer.  

PubMed

Nanotechnology has enabled the development of novel therapeutic and diagnostic strategies, such as advances in targeted drug delivery systems, versatile molecular imaging modalities, stimulus responsive components for fabrication, and potential theranostic agents in cancer therapy. Nanoparticle modifications such as conjugation with polyethylene glycol have been used to increase the duration of nanoparticles in blood circulation and reduce renal clearance rates. Such modifications to nanoparticle fabrication are the initial steps toward clinical translation of nanoparticles. Additionally, the development of targeted drug delivery systems has substantially contributed to the therapeutic efficacy of anti-cancer drugs and cancer gene therapies compared with nontargeted conventional delivery systems. Although multifunctional nanoparticles offer numerous advantages, their complex nature imparts challenges in reproducibility and concerns of toxicity. A thorough understanding of the biological behavior of nanoparticle systems is strongly warranted prior to testing such systems in a clinical setting. Translation of novel nanodrug delivery systems from the bench to the bedside will require a collective approach. The present review focuses on recent research efforts citing relevant examples of advanced nanodrug delivery and imaging systems developed for cancer therapy. Additionally, this review highlights the newest technologies such as microfluidics and biomimetics that can aid in the development and speedy translation of nanodrug delivery systems to the clinic. PMID:24550101

Babu, Anish; Templeton, Amanda K; Munshi, Anupama; Ramesh, Rajagopal

2014-06-01

112

The occasional case against broad dissemination and implementation: retaining a role for specialty care in the delivery of psychological treatments.  

PubMed

Mental illness imposes a staggering public health burden in the United States. Although the past 40 years have witnessed tremendous advances in the identification of evidence-based practices (EBPs) in psychological treatments, gaps persist between treatment in experimental settings and services available in the community. In response, considerable attention and large financial commitments have focused in recent years on broad dissemination and implementation efforts designed to improve the quality of psychological services delivered by a variety of generalist practitioners across practice settings. Increasingly, under the influence of the Patient Protection and Affordable Care Act, it is envisioned that these generalists will practice in integrated primary care settings. These advances hold enormous potential, and yet, given the tremendous diversity of mental health problems and human suffering, broad dissemination and implementation efforts to generalists alone may not be sufficient to adequately address the burden of mental illness. Some EBPs may prove too complex for universal dissemination, and the time and expense required for quality dissemination and implementation preclude large-scale training in the treatment of low base rate disorders. As dissemination and implementation efforts work to ensure a quality generalist mental health care workforce, herein we highlight the vital need for available specialty care in the delivery of psychological treatments. Given traditional barriers that interfere with the accessibility of specialty care, we propose the transformative potential of a specialty behavioral telehealth care workforce, transacting with the generalist practitioner workforce to collectively ensure the highest quality and timely delivery of needed treatments to affected individuals. PMID:23915401

Comer, Jonathan S; Barlow, David H

2014-01-01

113

Treatment Planning and Delivery of External Beam Radiotherapy for Pediatric Sarcoma: The St. Jude Children's Research Hospital Experience  

SciTech Connect

Purpose: To describe and review the radiotherapy (RT) treatment planning and delivery techniques used for pediatric sarcoma patients at St. Jude Children's Research Hospital. The treatment characteristics serve as a baseline for future comparison with developing treatment modalities. Patients and Methods: Since January 2003, we have prospectively treated pediatric and young-adult patients with soft-tissue and bone sarcomas on an institutional Phase II protocol evaluating local control and RT-related treatment effects from external-beam RT (conformal or intensity-modulated RT; 83.4%), low-dose-rate brachytherapy (8.3%), or both (8.3%). Here we describe the treatment dosimetry and delivery parameters of the initial 72 patients (median, 11.6 years; range, 1.4-21.6 years). Results: Cumulative doses from all RT modalities ranged from 41.4 to 70.2 Gy (median, 50.4 Gy). Median D{sub 95} and V{sub 95} of the planning target volume of external-beam RT plans were, respectively, 93.4% of the prescribed dose and 94.6% of the target volume for the primary phase and 97.8% and 99.2% for the cone-down/boost phase. The dose-volume histogram statistics for 27 critical organs varied greatly. The spinal cord in 13 of 36 patients received dose >45 Gy (up to 52 Gy in 1 cc) because of tumor proximity. Conclusions: Planning and delivery of complex multifield external beam RT is feasible in pediatric patients with sarcomas. Improvements on conformity and dose gradients are still desired in many cases with sensitive adjacent critical structures. Long-term follow-up will determine the risk of local failure and the benefit of normal tissue avoidance for this population.

Hua Chiaho [Division of Radiation Oncology, Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN (United States)], E-mail: Chia-Ho.Hua@stjude.org; Gray, Jonathan M.; Merchant, Thomas E.; Kun, Larry E.; Krasin, Matthew J. [Division of Radiation Oncology, Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN (United States)

2008-04-01

114

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

115

Accurate vibrational spectra of methylpotassium using a hybrid CCSD(t)\\/b3LYP approach and a variational treatment  

Microsoft Academic Search

We present the structural parameters and vibrational spectra of CH3K computed using a hybrid approach in which CCSD(T) equilibrium values and harmonic wavenumbers are coupled to B3LYP anharmonic cubic and quartic terms in the framework of our variational treatment recently developed and presented for CH3Li. The obtained results confirm the assignment of several observed bands but suggest some revision of

Neil Gohaud; Didier Begue; Claude Pouchan

2005-01-01

116

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

117

Probenecid Treatment Enhances Retinal and Brain Delivery of N-4-Benzoylaminophenylsulfonylglycine, An Anionic Aldose Reductase Inhibitor  

PubMed Central

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 minutes 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 4 hr 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 1 hr was increased by about 11 fold (2580 vs 244 ng/gm; p<0.05). Further, following probenecid pretreatment, significant BAPSG levels were detectable in the brain (45 ± 20 ng/gm) at 1 hr, 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.

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

2009-01-01

118

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging  

PubMed Central

Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered.

2010-01-01

119

CT-on-rails-guided HDR brachytherapy: single-room, rapid-workflow treatment delivery with integrated image guidance.  

PubMed

Brachytherapy is an important component of multidisciplinary cancer care for a variety of solid tumors. Most systems require moving the patient to multiple locations for treatment planning and delivery after the applicator is placed. A dedicated computed tomography (CT)-on-rails brachytherapy suite was installed at our institution to allow image-guided brachytherapy and a rapid scan-plan-treat workflow that is well suited to a busy quaternary care medical center. The suite consists of an OR couch with CT-compatible insert, a CT-on-rails imaging unit, a Varian Varisource iX HDR afterloader and full anesthesia capabilities. The explicit goal was to provide the ability to perform applicator placement, CT-guided treatment planning, and treatment delivery efficiently and without moving the patient. The dedicated CT-on-rails suite for high-dose-rate brachytherapy offers image-guided brachytherapy capabilities with a rapid workflow that lends itself well to efficient, high-quality care that can meet the demands of a large-volume referral center capable of high patient throughput. PMID:24754589

Orcutt, Kevin P; Libby, Bruce; Handsfield, Lydia L; Moyer, Grace; Showalter, Timothy N

2014-03-01

120

Insights into the novel three 'D's of epilepsy treatment: drugs, delivery systems and devices.  

PubMed

Here, we review three 'D's--drugs, delivery systems and devices--that can selectively target not only brain regions but also abnormal cells in the epileptic nervous system. This review also offers insights into the novel molecular targets that enabled the development of new antiepileptic drugs with improved efficacy. Nanotechnology-based delivery systems and alert, diagnostic, surgical and brain stimulation devices designed for the control and management of epilepsy are also discussed. Although the application of the three 'D's continues to be valuable, this review also considers computer-aided software systems, with special emphasis on seizure detection and management. Finally, challenges that still loiter in the field and future prospects that, once accomplished, could lead to cures for epilepsy are addressed. PMID:20603226

Pathan, Shadab A; Jain, Gaurav K; Akhter, Sohail; Vohora, Divya; Ahmad, Farhan J; Khar, Roop K

2010-09-01

121

Collagen-hydroxyapatite/cisplatin drug delivery systems for locoregional treatment of bone cancer.  

PubMed

In this paper, the synthesis and characterization of novel cisplatin-loaded collagen (COLL)/hydroxyapatite (HA) composite materials are presented. The composite materials were designed to obtain a COLL: HA weight ratio close to the bone composition. The content of embedded cisplatin was chosen to assure a concentration of cisplatin of 6 and 10 ?M, respectively, into the culture media used in cell culture experiments. These cisplatin delivery systems were characterized by determining the physico-chemical properties of the composite material, the drug release process as well as their biological activity. Based on the in vitro data that showed the cytotoxic, anti-proliferative and anti-invasive activities of these multifunctional systems on G292 osteosarcoma cells in dependence on the cisplatin concentration released in culture medium, we conclude that the newly developed COLL/HA-cisplatin drug delivery system could be a feasible approach for locoregional chemotherapy of bone cancer. PMID:23547973

Andronescu, Ecaterina; Ficai, Anton; Albu, Madalina Georgiana; Mitran, Valentina; Sonmez, Maria; Ficai, Denisa; Ion, Raluca; Cimpean, Anisoara

2013-08-01

122

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

PubMed

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 degrees and 270 degrees with the MV beam off, and at 270 degrees 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. PMID:18561654

Adamson, Justus; Wu, Qiuwen

2008-05-01

123

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

PubMed Central

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° and 270° with the MV beam off, and at 270° 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

2008-01-01

124

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: What should be the policy?  

PubMed Central

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1–100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law–healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines.

Kateb, Babak; Chiu, Katherine; Black, Keith L.; Yamamoto, Vicky; Khalsa, Bhavraj; Ljubimova, Julia Y.; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio; Modo, Mike; Moore, David F.; Farahani, Keyvan; Okun, Michael S.; Prakash, Neal; Neman, Josh; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D.

2012-01-01

125

Pulmonary delivery of an ultra-fine oxytocin dry powder formulation: potential for treatment of postpartum haemorrhage in developing countries.  

PubMed

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

Prankerd, Richard J; Nguyen, Tri-Hung; 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

126

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.

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

127

Focused ultrasound induced blood-brain barrier disruption to enhance chemotherapeutic drugs (BCNU) delivery for glioblastoma treatment  

NASA Astrophysics Data System (ADS)

Focused ultrasound has been recently found to capable of temporally and reversibly disrupt local blood-brain barrier (BBB) and opens new frontier in delivering varies type of drugs into brain for central nerve system (CNS) disorder treatment. In this study, we aim to investigate the feasibility of delivering 1, 3-bits (2-chloroethyl) -1-nitrosourea (BCNU) to treat glioblastoma in animal models and evaluate whether this approach would gain treatment efficacy. Under the presence of microbubbles administration, a 400-kHz focused ultrasound was employed to deliver burst-tone ultrasonic energy stimulation to disrupt BBB in animal brains transcranially, and in-vivo monitored by magnetic-resonance imaging (MRI). C6-glioma cells were cultured and implanted into Sprague-Dawley rats as the brain-tumor model. BCNU deposited in brain was quantified by using high-performance liquid chromatography (HPLC), and brain tissues were examined histologically. MRI was employed to longitudinal evaluate the brain tumor treatment including the analysis of tumor progression and animal survival. We confirmed that the focused ultrasound, under the secure ultrasonic energy level, can significantly enhance the BCNU penetration through BBB over 300% than control without cause hemorrhage. Apparent improvement of treatment efficacy achieved by combining focused ultrasound with BCNU delivery, including significant suppression of tumor growth and a prolonged animal survival. This study highly support that this treatment strategy could be clinically-relevant and may help to provide another potential strategy in increasing local chemotherapeutic drugs for brain-tumor treatment.

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Huang, Chiung-Yin; Wang, Jiun-Jie; Wei, Kuo-Chen

2010-03-01

128

Multifunctional magnetic nanoparticles for synergistic enhancement of cancer treatment by combinatorial radio frequency thermolysis and drug delivery.  

PubMed

Few-layer, carbon-coated, iron (C/Fe) magnetic nanoparticles (MNPs) were synthesized with controlled sizes ranging from 7 to 9 nm. The additional loading of two anti-cancer drugs, doxorubicin and erlotinib, was achieved through - stacking onto the carbon shells. Controlled release of the drugs was successfully triggered by radio frequency (RF) heating or pH variation. Based on the experimental results, C/Fe MNPs act as heat-inducing agents and are able to thermally destroy cancer cells when RF is applied. It was found that the combination of anti-cancer drugs (in particular a low dose of doxorubicin) and RF treatment demonstrates a synergistic effect in inducing cell death in pancreatic cancer cells. Our findings demonstrate that MNPs can be used as highly efficient multimodal nanocarrier agents for an integrated approach to cancer treatment involving triggered delivery of antineoplastic drugs and RF-induced thermal therapy. PMID:23184783

Xu, Yang; Karmakar, Alokita; Heberlein, Wolf E; Mustafa, Thikra; Biris, Alexandru R; Biris, Alexandru S

2012-07-01

129

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.

2014-01-01

130

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.

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

2013-01-01

131

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

132

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.

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

2013-01-01

133

Intensity-modulated arc therapy to improve radiation dose delivery in the treatment of abdominal neuroblastoma.  

PubMed

The standard European radiotherapy technique for children with neuroblastoma is a conventional parallel opposed pair. This frequently results in compromise on planning target volume coverage to stay within normal tissue tolerances. This study investigates the use of an intensity-modulated arc therapy (IMAT) technique to improve dose distribution and allow better protocol compliance. Among 20 previously treated patients, ten had received the full prescribed dose with conventional planning (protocol compliant) and ten had a compromise on planning target volume coverage (protocol noncompliant). All patients were replanned with IMAT. Dosimetric parameters of the conventional radiotherapy and IMAT were compared. The dose received by 98% of the planning target volume, homogeneity and conformity indices were all improved with IMAT (p < 0.001). IMAT would have enabled delivery of the full protocol dose in eight out of ten protocol-noncompliant patients. IMAT may improve outcomes through improved protocol compliance and better dose distributions. PMID:23469979

Gains, Jennifer E; Stacey, Christopher; Rosenberg, Ivan; Mandeville, Henry C; Chang, Yen-Ch'ing; D'Souza, Derek; Moroz, Veronica; Wheatley, Keith; Gaze, Mark N

2013-03-01

134

Evaluation of unnatural cyclic amino acids as boron delivery agents for treatment of melanomas and gliomas.  

PubMed

Unnatural cyclic amino acids (UNAAs) are a new class of boron delivery agents that are in a pre-clinical stage of evaluation. In the present study, the biodistribution of racemic forms of the cis- and trans-isomers of the boronated UNAA 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) and 1-amino-3-boronocycloheptanecarboxylic acid (ABCHC) were evaluted in B16 melanoma bearing mice and this was compared to l-p-boronophenylalanine (BPA). Boron concentrations were determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES) at 2.5h following intraperitoneal (i.p.) injection of the test agents at a concentration equivalent to 24mg/B/kg. While all compounds attained comparable tumor boron concentrations, the tumor/blood (T/Bl) boron concentration ratios were far superior for both cis-ABCPC and cis-ABCHC compared to BPA (T/Bl=16.4, and 15.1 vs. 5.4). Secondary ion mass spectrometry (SIMS) imaging revealed that the cis-ABCPC delivered boron to the nuclei, as well as the cytoplasm of B16 cells. Next, a biodistribution study of cis-ABCPC and BPA was carried out in F98 glioma bearing rats following i.p. administration. Both compounds attained comparable tumor boron concentrations but the tumor/brain (T/Br) boron ratio was superior for cis-ABCPC compared to BPA (6 vs. 3.3). Since UNAAs are water soluble and cannot be metabolized by tumor cells, they could be potentially more effective boron delivery agents than BPA. Our data suggest that further studies are warranted to evaluate these compounds prior to the initiation of clinical studies. PMID:24393770

Barth, Rolf F; Kabalka, George W; Yang, Weilian; Huo, Tianyao; Nakkula, Robin J; Shaikh, Aarif L; Haider, Syed A; Chandra, Subhash

2014-06-01

135

Focused Ultrasound-Induced Blood-Brain Barrier Opening to Enhance Temozolomide Delivery for Glioblastoma Treatment: A Preclinical Study  

PubMed Central

The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.

Wei, Kuo-Chen; Chu, Po-Chun; Wang, Hay-Yan Jack; Huang, Chiung-Yin; Chen, Pin-Yuan; Tsai, Hong-Chieh; Lu, Yu-Jen; Lee, Pei-Yun; Tseng, I-Chou; Feng, Li-Ying; Hsu, Peng-Wei; Yen, Tzu-Chen; Liu, Hao-Li

2013-01-01

136

Target specific systemic delivery of TGF-? siRNA/(PEI-SS)-g-HA complex for the treatment of liver cirrhosis.  

PubMed

A target specific systemic delivery system of siRNA therapeutics was successfully developed using reducible polyethyleneimine grafted hyaluronic acid [(PEI-SS)-g-HA] conjugates. The PEI-SS was synthesized by Michael addition of low molecular weight PEI (MW = 2000) with cystaminebisacrylamide (CBA), and grafted to carboxyl groups of HA via amide bond formation after activation with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-hydroxybenzotriazole monohydrate (HOBt). The confocal microscopic and fluorometric analyses confirmed the effective cellular uptake of siRNA/(PEI-SS)-g-HA complex by HA receptor mediated endocytosis. In vitro gene silencing efficiency was ca. 80% in the presence of 10 vol% serum and ca. 50% in the presence of 50 vol% serum in B16F1 melanoma cells and activated hepatic stellate cells (HSCs). Furthermore, target specific systemic delivery of apolipoprotein B (ApoB) siRNA/(PEI-SS)-g-HA complex resulted in a drastically reduced ApoB mRNA level down to ca. 20% in a dose-dependent manner. Finally, TGF-? siRNA/(PEI-SS)-g-HA complex showed a feasible therapeutic effect on liver cirrhosis with a significantly reduced nodule formation, collagen content, and HSC number. The siRNA/(PEI-SS)-g-HA complex can be exploited for the target specific systemic treatment of various liver diseases. PMID:21481451

Park, Kitae; Hong, Sung Woo; Hur, Wonhee; Lee, Min-Young; Yang, Jeong-A; Kim, Sung Woo; Yoon, Seung Kew; Hahn, Sei Kwang

2011-07-01

137

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.

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

138

Design, fabrication and analysis of silicon hollow microneedles for transdermal drug delivery system for treatment of hemodynamic dysfunctions.  

PubMed

In this paper, we present design, fabrication and coupled multifield analysis of hollow out-of-plane silicon microneedles with piezoelectrically actuated microfluidic device for transdermal drug delivery (TDD) system for treatment of cardiovascular or hemodynamic disorders such as hypertension. The mask layout design and fabrication process of silicon microneedles and reservoir involving deep reactive ion etching (DRIE) is first presented. This is followed by actual fabrication of silicon hollow microneedles by a series of combined isotropic and anisotropic etching processes using inductively coupled plasma (ICP) etching technology. Then coupled multifield analysis of a MEMS based piezoelectrically actuated device with integrated silicon microneedles is presented. The coupledfield analysis of hollow silicon microneedle array integrated with piezoelectric micropump has involved structural and fluid field couplings in a sequential structural-fluid analysis on a three-dimensional model of the microfluidic device. The effect of voltage and frequency on silicon membrane deflection and flow rate through the microneedle is investigated in the coupled field analysis using multiple code coupling method. The results of the present study provide valuable benchmark and prediction data to fabricate optimized designs of the silicon hollow microneedle based microfluidic devices for transdermal drug delivery applications. PMID:20730492

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

2010-09-01

139

Helical tomotherapy-based STAT stereotactic body radiation therapy: Dosimetric evaluation for a real-time SBRT treatment planning and delivery program.  

PubMed

Stereotactic body radiation therapy (SBRT) treatments have high-dose gradients and even slight patient misalignment from the simulation to treatment could lead to target underdosing or organ at risk (OAR) overdosing. Daily real-time SBRT treatment planning could minimize the risk of geographic miss. As an initial step toward determining the clinical feasibility of developing real-time SBRT treatment planning, we determined the calculation time of helical TomoTherapy-based STAT radiation therapy (RT) treatment plans for simple liver, lung, and spine SBRT treatments to assess whether the planning process was fast enough for practical clinical implementation. Representative SBRT planning target volumes for hypothetical liver, peripheral lung, and thoracic spine lesions and adjacent OARs were contoured onto a planning computed tomography scan (CT) of an anthropomorphic phantom. Treatment plans were generated using both STAT RT "full scatter" and conventional helical TomoTherapy "beamlet" algorithms. Optimized plans were compared with respect to conformality index (CI), heterogeneity index (HI), and maximum dose to regional OARs to determine clinical equivalence and the number of required STAT RT optimization iterations and calculation times were determined. The liver and lung dosimetry for the STAT RT and standard planning algorithms were clinically and statistically equivalent. For the liver lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.04 and 1.04 and HI of 1.03 and 1.03, respectively. For the lung lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.05 and 1.03 and HI of 1.05and 1.05, respectively. For spine lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.15 and 1.14 and HI of 1.22 and 1.14, respectively. There was no difference between treatment algorithms with respect to maximum doses to the OARs. The STAT RT iteration time with current treatment planning systems is 45 sec, and the treatment planning required 3 iterations or 135 sec for STAT RT liver and lung SBRT plans and 7 iterations or 315 sec for STAT RT spine SBRT plans. Helical TomoTherapy-based STAT RT treatment planning with the "full scatter" algorithm provides levels of dosimetric conformality, heterogeneity, and OAR avoidance for SBRT treatments that are clinically equivalent to those generated with the Helical TomoTherapy "beamlet" algorithm. STAT RT calculation times for simple SBRT treatments are fast enough to warrant further investigation into their potential incorporation into an SBRT program with daily real-time planning. Development of methods for accurate target and OAR determination on megavoltage computed tomography scans incorporating high-resolution diagnostic image co-registration software and CT detector-based exit dose measurement for quality assurance are necessary to build a real-time SBRT planning and delivery program. PMID:21055611

Dunlap, Neal; McIntosh, Alyson; Sheng, Ke; Yang, Wensha; Turner, Benton; Shoushtari, Asal; Sheehan, Jason; Jones, David R; Lu, Weigo; Ruchala, Keneth; Olivera, Gustavo; Parnell, Donald; Larner, James L; Benedict, Stanley H; Read, Paul W

2010-01-01

140

Helical Tomotherapy-Based STAT Stereotactic Body Radiation Therapy: Dosimetric Evaluation for a Real-Time SBRT Treatment Planning and Delivery Program  

SciTech Connect

Stereotactic body radiation therapy (SBRT) treatments have high-dose gradients and even slight patient misalignment from the simulation to treatment could lead to target underdosing or organ at risk (OAR) overdosing. Daily real-time SBRT treatment planning could minimize the risk of geographic miss. As an initial step toward determining the clinical feasibility of developing real-time SBRT treatment planning, we determined the calculation time of helical TomoTherapy-based STAT radiation therapy (RT) treatment plans for simple liver, lung, and spine SBRT treatments to assess whether the planning process was fast enough for practical clinical implementation. Representative SBRT planning target volumes for hypothetical liver, peripheral lung, and thoracic spine lesions and adjacent OARs were contoured onto a planning computed tomography scan (CT) of an anthropomorphic phantom. Treatment plans were generated using both STAT RT 'full scatter' and conventional helical TomoTherapy 'beamlet' algorithms. Optimized plans were compared with respect to conformality index (CI), heterogeneity index (HI), and maximum dose to regional OARs to determine clinical equivalence and the number of required STAT RT optimization iterations and calculation times were determined. The liver and lung dosimetry for the STAT RT and standard planning algorithms were clinically and statistically equivalent. For the liver lesions, 'full scatter' and 'beamlet' algorithms showed a CI of 1.04 and 1.04 and HI of 1.03 and 1.03, respectively. For the lung lesions, 'full scatter' and 'beamlet' algorithms showed a CI of 1.05 and 1.03 and HI of 1.05and 1.05, respectively. For spine lesions, 'full scatter' and 'beamlet' algorithms showed a CI of 1.15 and 1.14 and HI of 1.22 and 1.14, respectively. There was no difference between treatment algorithms with respect to maximum doses to the OARs. The STAT RT iteration time with current treatment planning systems is 45 sec, and the treatment planning required 3 iterations or 135 sec for STAT RT liver and lung SBRT plans and 7 iterations or 315 sec for STAT RT spine SBRT plans. Helical TomoTherapy-based STAT RT treatment planning with the 'full scatter' algorithm provides levels of dosimetric conformality, heterogeneity, and OAR avoidance for SBRT treatments that are clinically equivalent to those generated with the Helical TomoTherapy 'beamlet' algorithm. STAT RT calculation times for simple SBRT treatments are fast enough to warrant further investigation into their potential incorporation into an SBRT program with daily real-time planning. Development of methods for accurate target and OAR determination on megavoltage computed tomography scans incorporating high-resolution diagnostic image co-registration software and CT detector-based exit dose measurement for quality assurance are necessary to build a real-time SBRT planning and delivery program.

Dunlap, Neal; McIntosh, Alyson; Sheng Ke; Yang Wensha; Turner, Benton; Shoushtari, Asal [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Sheehan, Jason [Department of Neurosurgery, University of Virginia, Charlottesville, VA (United States); Jones, David R. [Department of Surgery, University of Virginia, Charlottesville, VA (United States); Lu Weigo; Ruchala, Keneth; Olivera, Gustavo; Parnell, Donald [TomoTherapy, Inc., Madison, WI (United States); Larner, James L.; Benedict, Stanley H. [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Read, Paul W., E-mail: pwr3u@virginia.ed [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States)

2010-01-01

141

Infertility Treatment, ART and IUI Procedures and Delivery Outcomes: How Important is Selection?  

Microsoft Academic Search

Medical treatments such as Intra-Uterine Insemination (IUI) and Assisted Reproduction Technology (ART) that help otherwise infertile couples to get pregnant are highly successful and widely used these days. While highly successful, there have been concerns regarding the safety of these procedures and their effect on maternal and neonatal outcomes. Specifically, it has been observed that these treatments significantly increase the

Pooja G. Mookim; Randall P. Ellis; Ariella Kahn-Lang

2010-01-01

142

The VACS Index Accurately Predicts Mortality and Treatment Response among Multi-Drug Resistant HIV Infected Patients Participating in the Options in Management with Antiretrovirals (OPTIMA) Study  

PubMed Central

Objectives The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study. Methods Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel’s C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality. Results Both the Restricted Index (c?=?0.70) and VACS Index (c?=?0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI?=?23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14–0.49) and 0.39(95% CI 0.22–0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27–3.38) and 1.51 (95%CI 0.90–2.53) for the 25% least improved scores. Conclusions The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research.

Brown, Sheldon T.; Tate, Janet P.; Kyriakides, Tassos C.; Kirkwood, Katherine A.; Holodniy, Mark; Goulet, Joseph L.; Angus, Brian J.; Cameron, D. William; Justice, Amy C.

2014-01-01

143

Treatment of Breast Tumors using Pulsed HIFU for Delivery and Activation of Sonosensitizers.  

National Technical Information Service (NTIS)

High intensity focused ultrasound (HIFU) has been combined with a Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. In vitro tests have shown that a short treatment (less than...

B. E. O'Neill

2009-01-01

144

Developing Treatment Plan Support in Outpatient Health Care Delivery with Decision Trees Technique  

Microsoft Academic Search

\\u000a This paper presents treatment plan support (TPS) development with the aim to support treatment decision making for physicians\\u000a during outpatient-care giving to patients. Evidence-based clinical data from system database was used. The TPS predictive\\u000a modeling was generated using decision trees technique, which incorporated predictor variables: patient’s age, gender, racial,\\u000a marital status, occupation, visit complaint, clinical diagnosis and final diagnosed diseases;

Shahriyah Nyak Saad Ali; Ahmad Mahir Razali; Azuraliza Abu Bakar; Nur Riza Suradi

2010-01-01

145

Patient-centred tuberculosis treatment delivery under programmatic conditions in Tanzania: a cohort study  

Microsoft Academic Search

BACKGROUND: Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health

Saidi Egwaga; Abdallah Mkopi; Nyagosya Range; Vera Haag-Arbenz; Amuri Baraka; Penny Grewal; Frank Cobelens; Hassan Mshinda; Fred Lwilla; Frank van Leth

2009-01-01

146

Colon drug delivery.  

PubMed

Oral drug delivery to the colon has attracted significant attention during the past 20 years. Colon targeting is recognised to have several therapeutic advantages, such as the oral delivery of drugs that are destroyed by the stomach acid and/or metabolised by pancreatic enzymes. Sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Local treatment of colonic pathologies, such as ulcerative colitis, colorectal cancer and Crohn's disease, is more effective with the delivery of drugs to the affected area. Likewise, colonic delivery of vermicides and colonic diagnostic agents requires smaller doses. This article aims to provide an insight into the design and manufacturing considerations, and an evaluation of colonic drug delivery systems in order to understand why there are still few delivery technologies that have reached the market, despite intensive research in this field. For this purpose, various approaches to colon-specific drug delivery are discussed. PMID:16370944

Van den Mooter, Guy

2006-01-01

147

Treatment planning and delivery of shell dose distribution for precision irradiation  

NASA Astrophysics Data System (ADS)

The motivation for shell dose irradiation is to deliver a high therapeutic dose to the surrounding supplying blood-vessels of a lesion. Our approach's main utility is in enabling laboratory experiments to test the much disputed hypothesis about tumor vascular damage. That is, at high doses, tumor control is driven by damage to the tumor vascular supply and not the damage to the tumor cells themselves. There is new evidence that bone marrow derived cells can reconstitute tumor blood vessels in mice after irradiation. Shell dosimetry is also of interest to study the effect of radiation on neurogenic stem cells that reside in small niche surface of the mouse ventricles, a generalized form of shell. The type of surface that we are considering as a shell is a sphere which is created by intersection of cylinders. The results are then extended to create the contours of different organ shapes. Specifically, we present a routine to identify the 3-D structure of a mouse brain, project it into 2-D contours and convert the contours into trajectories that can be executed by our platform. We use the Small Animal Radiation Research Platform (SARRP) to demonstrate the dose delivery procedure. The SARRP is a portable system for precision irradiation with beam sizes down to 0.5 mm and optimally planned radiation with on-board cone-beam CT guidance.

Matinfar, Mohammad; Iyer, Santosh; Ford, Eric; Wong, John; Kazanzides, Peter

2010-03-01

148

Competence in aspects of behavioral treatment and consultation: implications for service delivery and graduate training.  

PubMed Central

This study examined the extent to which competence in applying behavioral procedures (time-out from positive reinforcement) was sufficient to establish competence in teaching others to apply the same procedures. During baseline, graduate students attempted to instruct parents with a history of child abuse and neglect in the use of time-out. Students were then instructed in the use of time-out until they achieved proficiency in a role-play context. They then reattempted to instruct the parents. Finally, the students were instructed in certain consultation skills (i.e., teaching others to apply behavioral procedures) and again attempted to instruct parents in the application of time-out. Observations of students' consultation skills, parents' proficiency at administering time-out, and children's compliance to parental instructions revealed that explicit training in behavioral consulting skills was necessary to produce improvements in these behaviors. Students proficiency at administering time-out was insufficient to enable them to instruct others in its application. These results were corroborated by surveys of both students and staff. The implications for graduate training and service delivery are discussed.

McGimsey, J F; Greene, B F; Lutzker, J R

1995-01-01

149

Heat treatment improves antigen-specific T cell activation after protein delivery by several but not all yeast genera.  

PubMed

A central prerequisite in using yeast as antigen carrier in vaccination is its efficient interaction with cellular components of the innate immune system, mainly mediated by cell surface structures. Here, we investigated the distribution of major yeast cell wall components such as mannan, ?-glucan and chitin of four different and likewise biotechnologically relevant yeasts (Saccharomyces, Pichia, Kluyveromyces and Schizosaccharomyces) and analyzed the influence of heat-treatment on ?-1,3-glucan exposure at the outer yeast cell surface as well as the amount of yeast induced reactive oxygen species (ROS) production by antigen presenting cells (APC) in human blood. We found that yeasts significantly differ in the distribution of their cell wall components and that heat-treatment affected both, cell wall composition and yeast-induced ROS production by human APCs. We further show that heat-treatment modulates the activation of antigen specific memory T cells after yeast-mediated protein delivery in different ways and thus provide additional support of using yeast as vehicle for the development of novel T cell vaccines. PMID:24674665

Bazan, Silvia Boschi; Breinig, Tanja; Schmitt, Manfred J; Breinig, Frank

2014-05-01

150

A preliminary study of painless and effective transdermal botulinum toxin A delivery by jet nebulization for treatment of primary hyperhidrosis  

PubMed Central

Background Hyperhidrosis is a chronic disease characterized by increased sweat production. Local injections of botulinum toxin A (BTX-A) have been extensively used for treatment of primary hyperhidrosis (idiopathic). The current treatment for this condition involves several intradermal injections, resulting in poor patient compliance due to injection-related pain. Therefore, new protocols, including an improved anesthetic regimen, are required. Aim We designed the present study to determine whether JetPeel™-3, a medical device used for transdermal delivery of drugs by jet nebulization, could be used to deliver lidocaine prior to the standard multiple BTX-A injections or deliver lidocaine together with BTX-A in order to determine the protocol giving better results in terms of procedure-related pain, sweating, and patient satisfaction in subjects affected by primary axillary, palmar or plantar hyperhidrosis. Materials and methods Twenty patients with a visual analog scale (VAS) sweating score ? 8 cm were randomized to receive lidocaine 2% (5 mL) delivered by JetPeel™-3 followed by multiple injections of BTX-A (100 units) or lidocaine 2% (5 mL) and BTX-A (50 units) delivered together by JetPeel™-3. Effect of treatment on sweating was measured by VAS (0= minimum sweating; 10= maximum sweating) at 3-month follow-up. Pain induced by the procedure was assessed by VAS (0= minimum pain; 10= maximum pain) immediately after the procedure. Patient satisfaction was assessed at 3-month follow-up using a 5-point scale (1= not at all satisfied; 2= not satisfied; 3= partially satisfied; 4= satisfied; 5= highly satisfied). Results Both treatment modalities reduced sweating at 3-month follow-up, if compared with baseline (all P<0.001). Delivery of lidocaine and BTX-A by JetPeel™-3 resulted in lower procedure-related pain and reduced sweating, if compared with lidocaine delivered by JetPeel™-3 followed by multiple BTX-A injections (all P<0.001). Patient satisfaction with the procedure was higher in the group receiving lidocaine and BTX-A treatment by JetPeel™-3, if compared with lidocaine delivered by JetPeel™-3 followed by multiple BTX-A injections (P<0.001). No side effects were observed in both groups. Conclusion Lidocaine and BTX-A can be safely delivered together by JetPeel™-3 to treat primary palmar, plantar and axillary hyperhidrosis, resulting in lower procedure-related pain, improved sweating and higher patient satisfaction, if compared with lidocaine delivered by JetPeel™-3 followed by standard BTX-A injection therapy. Our protocol delivering lidocaine and BTX-A together by JetPeel™-3 requires a reduced quantity of BTX-A, further supporting the use of the transdermal drug delivery by jet nebulization over standard injection therapy for treatment of primary hyperhidrosis.

Iannitti, Tommaso; Palmieri, Beniamino; Aspiro, Anna; Di Cerbo, Alessandro

2014-01-01

151

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.

Borenstein, Jeffrey T.

2011-01-01

152

SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment.  

PubMed

Due to low charge density and stiff backbone structure, small interfering RNA (siRNA) has inherently poor binding ability to cationic polymers and lipid carriers, which results in low siRNA loading efficiency and limits siRNA success in clinical application. Here, siRNA-phospholipids conjugates are developed, which integrate the characteristics of the two phospholipids to self-assemble via hydrophilic siRNA and hydrophobic phospholipid tails to overcome the siRNA's stiff backbone structures and enhance the siRNA loading efficiency. In this study, the thiol-modified sense and antisense siRNA are chemically conjugated with phospholipids to form sense and antisense siRNA-phospholipid, and then these sense or antisense siRNA-phospholipids with equal amounts are annealed to generate siRNA-phospholipids. The siRNA-phospholipids can serve dual functions as agents that can silence gene expression and as a component of nanoparticles to embed hydrophobic anticancer drugs to cure tumor. siRNA-phospholipids together with cationic lipids and DSPE-PEG2000 fuse around PLGA to form siRNA-phospholipids enveloped nanoparticles (siRNA-PCNPs), which can deliver siRNAs and hydrophobic anticancer drugs into tumor. In animal models, intravenously injected siRNA-PCNPs embedded DOX (siPlk1-PCNPs/DOX) is highly effective in inhibiting tumor growth. The results indicate that the siRNA-PCNPs can be potentially applied as a safe and efficient gene and anticancer drug delivery carrier. PMID:24797882

Liu, Hongmei; Li, Yan; Mozhi, Anbu; Zhang, Liang; Liu, Yilan; Xu, Xia; Xing, Jianmin; Liang, Xingjie; Ma, Guanghui; Yang, Jun; Zhang, Xin

2014-08-01

153

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

154

The Association Between Program Characteristics and Service Delivery in Assertive Community Treatment  

Microsoft Academic Search

The authors describe the relationship between service intensity and staffing, organizational, client, and site characteristics in 19 programs based on the Thresholds Bridge adaptation of the assertive community treatment (ACT) model. Pearson correlations were examined between 14 program characteristics and intensity of ACT services. Several staffing and organizational attributes were related to service intensity: larger team size, shared caseloads, greater

John H. McGrew; Gary R. Bond

1997-01-01

155

Predictors of Placement Outcomes in Treatment Foster Care: Implications for Foster Parent Selection and Service Delivery  

Microsoft Academic Search

Treatment foster care (TFC) is a normalizing environment in which to treat those children whose particular needs are not addressed in traditional foster care and for whom an institutional setting is a restrictive and unnecessary alternative. However, when the foster care placements of these emotionally and behaviorally disturbed children fail, as they often do, the children are shifted from one

Richard E. Redding; Carrie Fried; Preston A. Britner

2000-01-01

156

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

157

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.

Moore, Johanna C; Miner, James R

2012-01-01

158

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

159

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

PubMed

In this paper, we present design of a transdermal drug delivery system for treatment of cardiovascular or hemodynamic disorders such as hypertension. The system comprises of integrated control electronics and microelectromechanical system devices such as micropump, micro blood pressure sensor and microneedle array. The objective is to overcome the limitations of oral therapy such as variable absorption profile and the need for frequent dosing, by fabricating a safe, reliable and cost effective transdermal drug delivery system to dispense various pharmacological agents through the skin for treatment of hemodynamic dysfunction such as hypertension. Moreover, design optimization of a piezoelectrically actuated valveless micropump is presented for the drug delivery system. Because of the complexity in analysis of piezoelectric micropump, which involves structural and fluid field couplings in a complicated geometrical arrangement, finite element (FE) numerical simulation rather than an analytical system has been used. The behavior of the piezoelectric actuator with biocompatible polydimethylsiloxane membrane is first studied by conducting piezoelectric analysis. Then the performance of the valveless micropump is analyzed by building a three dimensional electric-solid-fluid model of the micropump. The effect of geometrical dimensions on micropump characteristics and efficiency of nozzle/diffuser elements of a valveless micropump is investigated in the transient analysis using multiple code coupling method. The deformation results of the membrane using multifield code coupling analysis are in good agreement with analytical as well as results of single code coupling analysis of a piezoelectric micropump. The analysis predicts that to enhance the performance of the micropump, diffuser geometrical dimensions such as diffuser length, diffuser neck width and diffuser angle need to be optimized. Micropump flow rate is not strongly affected at low excitation frequencies from 10 to 200 Hz. The excitation voltage is the more dominant factor that affects the flow rate of the micropump as compared with the excitation frequency. However, at extremely high excitation frequencies beyond 8,000 Hz, the flow rate drops as the membrane exhibits multiple bending peaks which is not desirable for fluid flow. Following the extensive numerical analysis, actual fabrication and performance characterization of the micropump is presented. The performance of the micropump is characterized in terms of piezoelectric actuator deflection and micropump flow rate at different operational parameters. The set of multifield simulations and experimental measurement of deflection and flow rate at varying voltage and excitation frequency is a significant advance in the study of the electric-solid-fluid coupled field effects as it allows transient, three dimensional piezoelectric and fluid analysis of the micropump thereby facilitating a more realistic multifield analysis. The results of the present study will also help to conduct relevant strength duration tests of integrated drug delivery device with micropump and microneedle array in future. PMID:19030990

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

2008-12-01

160

Formulation and preliminary in vivo dog studies of a novel drug delivery system for the treatment of periodontitis.  

PubMed

A novel drug delivery system for the treatment of periodontitis was developed using two components. The first was tetracycline base loaded into the microtubular excipient halloysite, which was coated with chitosan to further retard drug release. Encapsulation efficiencies of 32.5% were achieved with the loading procedure, with tetracycline base showing in vitro release for up to 50 days in simulated gingival crevicular fluid. The second component developed was a vehicle for the drug loaded coated halloysite, which was primarily based on the thermoresponsive polymer, poloxamer 407. A concentration of 20% was chosen with the thermoresponsivity of the system modified using PEG 20,000 so that the mobile product at room temperature would gel by temperature rise following syringing into a periodontal pocket. Retention of the overall system in the pocket was further improved by the addition of octyl cyanoacrylate (OCA). The thermoresponsivity of the poloxamer 407 system proved to be sensitive to the presence of added excipients with the levels of PEG 20,000 and OCA requiring modification in the presence of the halloysite component. A final formulation was developed which consisted of 200 mg of halloysite double loaded with tetracycline base and coated with chitosan, suspended in 1 ml of poloxamer 407 20% (w/w), PEG 20,000 0.5% (w/w), OCA 1.0% (w/w), water to 100%, adjusted to pH 4. The syringeability of this formulation at various temperatures was evaluated to ensure ease of delivery to the periodontal pocket. A stability study was performed to examine the change in thermoresponsivity over time, with the final formulation found to be stable for at least 9 months when stored at room temperature (approximately 20 degrees C). This formulation offered ease of delivery to the periodontal pocket and sustained release of the antibiotic for up to 6 weeks. The formulation had preliminary in vivo testing performed in dogs to determine levels of drug release, antimicrobial activity and retentive ability of the product. A wound pocket creation model was developed for the purposes of the trial. The product was easy to deliver to the pockets with application times of less than 1 min. Results showed the product was retained in the pocket for up to 6 weeks with effective tetracycline levels released locally over this time period, which achieved good antibacterial activity. PMID:15072793

Kelly, H M; Deasy, P B; Ziaka, E; Claffey, N

2004-04-15

161

Rapid delivery of diazepam from supersaturated solutions prepared using prodrug/enzyme mixtures: toward intranasal treatment of seizure emergencies.  

PubMed

Current treatments for seizure emergencies, such as status epilepticus, include intravenous or rectal administration of benzodiazepines. While intranasal delivery of these drugs is desirable, the small volume of the nasal cavity and low drug solubility pose significant difficulties. Here, we prepared supersaturated diazepam solutions under physiological conditions and without precipitation, using a prodrug/enzyme system. Avizafone, a peptide prodrug of diazepam, was delivered with--Aspergillus oryzae (A.O.) protease, an enzyme identified from a pool of hydrolytic enzymes in assay buffer, pH 7.4 at 32°C. This enzyme converted avizafone to diazepam at supersaturated concentrations. In vitro permeability studies were performed at various prodrug/enzyme ratios using Madin-Darby canine kidney II-wild type (MDCKII-wt) monolayers, a representative model of the nasal epithelium. Monolayer integrity was examined using TEER measurement and the lucifer yellow permeability assay. Prodrug/drug concentrations were measured using HPLC. Enzyme kinetics with avizafone-protease mixtures revealed K(M)?=?1,501?±?232 ?M and V(max)?=?1,369?±?94 ?M/s. Prodrug-protease mixtures, when co-delivered apically onto MDCKII-wt monolayers, showed 2-17.6-fold greater diazepam flux (S?=?1.3-15.3) compared to near-saturated diazepam (S?=?0.7). Data for prodrug conversion upstream (apical side) and drug permeability downstream (basolateral side) fitted reasonably well to a previously developed in vitro two compartment pharmacokinetic model. Avizafone-protease mixtures resulted in supersaturated diazepam in less than 5 min, with the rate and extent of supersaturation determined by the prodrug/enzyme ratio. Together, these results suggest that an intranasal avizafone-protease system may provide a rapid and alternative means of diazepam delivery. PMID:24700272

Kapoor, Mamta; Winter, Tate; Lis, Lev; Georg, Gunda I; Siegel, Ronald A

2014-05-01

162

Verification of dose delivery for a prostate sIMRT treatment using a SLIC–EPID  

Microsoft Academic Search

The current work focuses on the verification of transmitted dose maps, measured using a scanning liquid ionization chamber–electronic portal imaging device (SLIC–EPID) for a typical step-and-shoot prostate IMRT treatment using an anthropomorphic phantom at anterior–posterior (A–P), and several non-zero gantry angles. The dose distributions measured using the SLIC–EPID were then compared with those calculated in the modelled EPID for each

Mohammad Mohammadi; Eva Bezak; Paul Reich

2008-01-01

163

Evaluation of a bioresorbable drug delivery system for the treatment of hepatocellular carcinoma.  

PubMed

Hepatocellular carcinoma (HCC) represents a major global health burden. Typically HCC responds poorly to chemotherapy, and such approaches to treat HCC are commonly associated with severe hepatic and/or systemic toxicity. The aim of this study was to evaluate a porous resorbable silica-calcium phosphate nanocomposite (SCPC) as a controlled release vehicle for cisplatin. Particles of two different formulations-SCPC50 and SCPC75, containing 19.49 and 32.9 mol % silica, respectively-were loaded with cisplatin by immersion treatment and pressed into discs. In vitro release kinetics studies of cisplatin from SCPC50 and SCPC75 demonstrated an initial burst release of 0.39 ± 0.04 mg (of the 1.49 mg total loaded) and 0.87 ± 0.07 mg (of the 2.34 mg total loaded), respectively. Over the following 44-day period. SCPC75-cisplatin hybrid produced a significantly higher sustained cisplatin release than that released from SCPC50. Cisplatin release correlated well with the surface area, and silica dissolution kinetics of the SCPC carrier. Treatment of rat HCC cells (H4IIE) with cisplatin released from SCPC-cisplatin hybrids induced apoptotic cell death in H4IIE cells in vitro. Results of this study suggest that SCPC composites may be of potential use for the treatment of HCC in vivo. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: , 2011. PMID:22105845

Vedantham, Kumar; Swet, Jacob H; McKillop, Iain H; El-Ghannam, Ahmed

2011-11-21

164

Long-Term Results of Radiofrequency Energy Delivery for the Treatment of GERD: Results of a Prospective 48-Month Study  

PubMed Central

Since 2000, radiofrequency (RF) energy treatment has been increasingly offered as an alternative option to invasive surgical procedures for selected patients with gastroesophageal reflux disease (GERD). Out of 69 patients treated since June 2002 to December 2007 with the Stretta procedure, 56 of them reached by the end of 2010 a 48-month followup. RF treatment significantly improved heartburn scores, GERD-specific quality of life scores, and general quality of life scores at 24 and 48 months in 52 out of 56 patients (92,8%). At each control time both mean heartburn and GERD HRQL scores decreased (P = 0.001 and P = 0.003, resp.) and both mental SF-36 and physical SF-36 ameliorated (P = 0.001 and 0.05, resp.). At 48 months, 41 out of 56 patients (72,3%) were completely off PPIs. Morbidity was minimal, with only one relevant but transient complication. According to other literature data, this study shows that RF delivery to LES is safe and durably improves symptoms and quality of life in well-selected GERD patients.

Dughera, Luca; Navino, Monica; Cassolino, Paola; De Cento, Mariella; Cacciotella, Luca; Cisaro, Fabio; Chiaverina, Michele

2011-01-01

165

Agonist-dependent delivery of M(2) muscarinic acetylcholine receptors to the cell surface after pertussis toxin treatment.  

PubMed

The internalization of the M(2) muscarinic cholinergic receptor (mAChR) proceeds through an atypical pathway that is independent of arrestin and clathrin function and shows a unique sensitivity to dynamin when the receptor is expressed in human embryonic kidney 293 cells. In this report we demonstrate that the internalization of the M(2) mAChR was modulated by activation of heterotrimeric G proteins, because treatment with pertussis toxin, which ADP-ribosylates G proteins of the G(i/o) family, caused a significant delay in the onset of internalization of the M(2) mAChR. The effects of pertussis toxin could not be explained by alteration of the agonist-dependent phosphorylation of the M(2) mAChR. The modulation of internalization by pertussis toxin was revealed to be due to recruitment of intracellular receptors to the cell surface upon agonist treatment. Pretreatment with pertussis toxin also greatly increased both the rate and extent of recovery of M(2) mAChRs to the cell surface after agonist-mediated internalization. These results demonstrate a novel aspect involved in the regulation of GPCRs. As with the tightly controlled internalization of GPCRs, the delivery of GPCRs to the cell surface is also highly regulated. PMID:11306711

Roseberry, A G; Bünemann, M; Elavunkal, J; Hosey, M M

2001-05-01

166

Combined adenovirus-mediated nitroreductase gene delivery and CB1954 treatment: a well-tolerated therapy for established solid tumors.  

PubMed

Gene-directed enzyme prodrug therapy (GDEPT) is a refinement of cancer chemotherapy that generates a potent cell-killing drug specifically in tumor cells by enzymatic activation of an inert prodrug. We describe in vivo studies that evaluate the efficacy and safety of intratumoral (i.t.) injection of an adenovirus vector (CTL102) expressing Escherichia coli nitroreductase (NTR) combined with systemic prodrug (CB1954) treatment. A single i.t. injection of CTL102 (7.5 x 10(9) to -2 x 10(10) particles) followed by CB1954 treatment produced clear anti-tumor effects in subcutaneous (s.c.) xenograft models of four cancers that are likely candidates for GDEPT (i.e., primary liver, head and neck, colorectal and prostate). Virus dose-response studies (s.c. liver model) revealed a steep increase and subsequent rapid plateauing of both NTR gene delivery and anti-tumor efficacy. Evidence of minor virus spread (toxicity) was observed in a s.c. head and neck xenograft model. This was eliminated by passive immunization with neutralizing anti-Ad5 antibodies prior to virus injection without reducing the magnitude of the anti-tumor effect. Preexisting anti-Ad5 neutralizing antibodies may therefore be an advantage rather than an issue in the clinical use of this new therapy. PMID:11237680

Djeha, A H; Thomson, T A; Leung, H; Searle, P F; Young, L S; Kerr, D J; Harris, P A; Mountain, A; Wrighton, C J

2001-02-01

167

Verification of dose delivery for a prostate sIMRT treatment using a SLIC-EPID.  

PubMed

The current work focuses on the verification of transmitted dose maps, measured using a scanning liquid ionization chamber-electronic portal imaging device (SLIC-EPID) for a typical step-and-shoot prostate IMRT treatment using an anthropomorphic phantom at anterior-posterior (A-P), and several non-zero gantry angles. The dose distributions measured using the SLIC-EPID were then compared with those calculated in the modelled EPID for each segment/subfield and also for the corresponding total fields using a gamma function algorithm with a distance to agreement and dose difference criteria of 2.54mm and 3%, respectively. PMID:18583141

Mohammadi, Mohammad; Bezak, Eva; Reich, Paul

2008-12-01

168

Substrate-mediated delivery of microRNA-145 through a polysorbitol-based osmotically active transporter suppresses smooth muscle cell proliferation: implications for restenosis treatment.  

PubMed

Smooth muscle cells (SMCs) can grow over a stent surface and block blood flow through the stent, resulting in restenosis. MicroRNAs (miRNAs) are post-transcriptional regulators that contribute to cell proliferation, survival, and metabolism. Several miRNAs, including miR-145, have been identified that regulate vascular SMC proliferation and are down-regulated under conditions of proliferation. We hypothesized that SMC proliferation would be reduced or diminished if miR-145 expression was restored in SMCs. We designed a method to coat the stent surface with miR-145 to suppress the over-growth of SMCs. For effective miRNA delivery, various types of nanocarriers were tested for enhanced transfection efficiency and biocompatibility in the case of surface-mediated delivery. Physico-chemical characterization of the prepared nanoparticles was performed, and the cell viabilities and transfection efficiencies of the carriers were studied and compared to select the most efficient carrier for substrate-mediated delivery. The polysorbitol-based osmotically active transporter (PSOAT) retained its transgene delivery capacity and had higher biocompatibility than the other tested carriers. We detected reporter and therapeutic gene expression at the stent surface following PSOAT-mediated delivery. SMC proliferation after the treatment with PSOAT/miR-145 nanoparticles (PMN) was monitored using the MTS assay, and miR-145 target gene expression after PMN treatment was measured by reverse transcription-polymerase chain reaction. PSOAT-mediated delivery of miR-145 was associated with efficient intracellular expression of the therapeutic gene. A drastic reduction in SMC proliferation was observed after PMN treatment, and miR-145 target proteins were down-regulated upon miR-145 replacement. PMID:24734509

Muthiah, Muthunarayanan; Islam, Mohammad Ariful; Cho, Chong Su; Hwang, Jun Eul; Chung, Ik-Joo; Park, In Kyu

2014-04-01

169

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.

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

2013-01-01

170

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

171

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

172

Delivery of Amphotericin B for Effective Treatment of Candida Albicans Induced Dermal Mycosis in Rats via Emulgel System: Formulation and Evaluation  

PubMed Central

Background: Amphotericin B (AmB) is among the gold standard antifungal agents used for the treatment of the wide range of fungal infections. However, the drug has various side- effects. Transdermal approach for the delivery of drug is one of the accepted and convenient modes of drug delivery. Aim: The current work was designed to formulate and to evaluate the AmB emulgel system. Materials and Methods: In the preparation of AmB emulgel, Carbopol 930 was used as a gel in this study. The formulation was evaluated for viscosity, spreadability, drug content, drug release and in vitro and in vivo antifungal testing. Results: AmB emulgel was found to penetrate skin effectively and without any irritation. Further, in vivo studies revealed effective therapeutic potential against Candida albicans induced dermal mycosis. Conclusions: The current work, for the first time, revealed effective delivery of AmB across the skin.

Ganeshpurkar, Aditya; Vaishya, Pooja; Jain, Sumeet; Pandey, Vikas; Bansal, Divya; Dubey, Nazneen

2014-01-01

173

Carbosilane dendrimers as gene delivery agents for the treatment of HIV infection.  

PubMed

Despite the use of siRNA in the downregulation of HIV-1 replication which has been reported, CD4 T lymphocytes are difficult to transfect with non-viral vectors. We determined whether second generation carbosilane dendrimers (2G-NN16 and 2G-03NN24) may be efficient transfectants in CD4 T lymphocytes. Dendrimers were also tested on macrophages to determine whether they can modify macrophage phenotype and induce an inflammatory response. The nanoconjugate formed by 2G-03NN24/siRNA-Nef presents the highest inhibition of HIV-1 replication. Dendrimers presented safety properties because they did not induce proliferation on CD4 T lymphocytes and decrease the release of TNF? and IL-12p40 by macrophages. Both dendrimers also decrease the phagocytosis activity. Additionally, 2G-03NN24 dendrimer decreases the CCL2 and CCR2 expression in macrophages. Carbosilane dendrimers 2G-NN16 and 2G-03NN24 can be used as efficient non-viral vectors for gene therapy applications, mainly in the treatment of HIV infection. PMID:24721235

Perisé-Barrios, Ana Judith; Jiménez, José Luis; Domínguez-Soto, Angeles; de la Mata, F Javier; Corbí, Angel L; Gomez, Rafael; Muñoz-Fernandez, María Ángeles

2014-06-28

174

Reactor beam calculations to determine optimum delivery of epithermal neutrons for treatment of brain tumors  

SciTech Connect

Studies were performed to assess theoretical tumor control probability (TCP) for brain-tumor treatment with boron neutron capture therapy (BNCT) using epithermal neutron sources from reactors. The existing epithermal-neutron beams at the Brookhaven Medical Research Reactor Facility (BMRR), the Petten High Flux Reactor Facility (HWR) and the Finnish Research Reactor 1 (FIR1) have been analyzed and characterized using common analytical and measurement methods allowing for this inter-comparison. Each of these three facilities is unique and each offers an advantage in some aspect of BNCT, but none of these existing facilities excel in all neutron-beam attributes as related to BNCT. A comparison is therefore also shown for a near-optimum reactor beam which does not currently exist but which would be feasible with existing technology. This hypothetical beam is designated BNCT-1 and has a spectrum similar to the FIR-1, the mono-directionality of the HFR and the intensity of the BMRR. A beam very similar to the BNCT-1 could perhaps be achieved with modification of the BMRR, HFR, or FIR, and could certainly be realized in a new facility with today`s technology.

Wheeler, F.J.; Nigg, D.W. [Idaho National Engineering & Environmental Lab., Idaho Falls, ID (United States); Capala, J. [Brookhaven National Lab., Upton, NY (United States)] [and others

1997-10-01

175

The effectiveness of a magnetic nanoparticle-based delivery system for BCNU in the treatment of gliomas.  

PubMed

This study describes the creation and characterization of drug carriers prepared using the polymer poly[aniline-co-N-(1-one-butyric acid) aniline] (SPAnH) coated on Fe(3)O(4) cores to form three types of magnetic nanoparticles (MNPs); these particles were used to enhance the therapeutic capacity and improve the thermal stability of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a compound used to treat brain tumors. The average hydrodynamic diameter of the MNPs was 89.2 ± 8.5 nm and all the MNPs displayed superparamagnetic properties. A maximum effective dose of 379.34 ?g BCNU could be immobilized on 1 mg of MNP-3 (bound-BCNU-3). Bound-BCNU-3 was more stable than free-BCNU when stored at 4 °C, 25 °C or 37 °C. Bound-BCNU-3 could be concentrated at targeted sites in vitro and in vivo using an externally applied magnet. When applied to brain tumors, magnetic targeting increased the concentration and retention of bound-BCNU-3. This drug delivery system promises to provide more effective tumor treatment using lower therapeutic doses and potentially reducing the side effects of chemotherapy. PMID:21030073

Hua, Mu-Yi; Liu, Hao-Li; Yang, Hung-Wei; Chen, Pin-Yuan; Tsai, Rung-Ywan; Huang, Chiung-Yin; Tseng, I-Chou; Lyu, Lee-Ang; Ma, Chih-Chun; Tang, Hsiang-Jun; Yen, Tzu-Chen; Wei, Kuo-Chen

2011-01-01

176

Fentanyl Buccal Tablet for the Treatment of Breakthrough Pain: Pharmacokinetics of Buccal Mucosa Delivery and Clinical Efficacy  

PubMed Central

The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc.) employs OraVescent® drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

Darwish, Mona; Hamed, Ehab; Messina, John

2010-01-01

177

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 15mg/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

178

A New Form of Intraoral Delivery of Antifungal Drugs for the Treatment of Denture-Induced Oral Candidosis  

PubMed Central

Objectives To monitor the release of the antifungal drugs Fluconazole, Chlorhexidine and a combination of the two from an auto-polymerized poly (methyl methacrylate) (PMMA) denture base resin; and to investigate the effect of the released drugs upon the growth of Candida albicans. Methods A high performance liquid chromatography-Ultra violet (HPLC-UV) method was used in the analysis of the released drugs into distilled water from PMMA discs doped with the antifungal drugs Fluconazole (10%), Chlorhexidine (10%) and a combination of the two drugs (5% each). The antifungal efficacy of the released drugs was monitored, microbiologically, employing “well” technique on a Saborauds culture medium inoculated with a resistant strain of Candida albicans. Results It was shown that Fluconazole, Chlorhexidine and the combination of the two drugs can be successfully incorporated with PMMA. It was found that the drugs leach steadily out of the PMMA resin into distilled water at mouth temperature and that sustained drug release continued throughout the 28 days test period. It was also shown that the released drugs demonstrated an antifungal activity against the resistant Candida albicans and this was most remarkable in the combined drugs samples. Conclusions The findings of this investigation have a clinical value in terms of their significant contribution to the treatment of fungal infections of the oral cavity. The sustained release of anti-fungal drugs from the PMMA resin clearly constitutes a new dosage form of these drugs via the poly (methyl methacrylate) delivery system.

Amin, Wala M.; Al-Ali, Muna H.; Salim, Nesreen A.; Al-Tarawneh, Sandra K.

2009-01-01

179

Cardiac-targeted delivery of regulatory RNA molecules and genes for the treatment of heart failure  

PubMed Central

Ribonucleic acid (RNA) in its many facets of structure and function is becoming more fully understood, and, therefore, it is possible to design and use RNAs as valuable tools in molecular biology and medicine. Understanding of the role of RNAs within the cell has changed dramatically during the past few years. Therapeutic strategies based on non-coding regulatory RNAs include RNA interference (RNAi) for the silencing of specific genes, and microRNA (miRNA) modulations to alter complex gene expression patterns. Recent progress has allowed the targeting of therapeutic RNAi to the heart for the treatment of heart failure, and we discuss current strategies in this field. Owing to the peculiar biochemical properties of small RNA molecules, the actual therapeutic translation of findings in vitro or in cell cultures is more demanding than with small molecule drugs or proteins. The critical requirement for animal studies after pre-testing of RNAi tools in vitro likewise applies for miRNA modulations, which also have complex consequences for the recipient that are dependent on stability and distribution of the RNA tools. Problems in the field that are not yet fully solved are the prediction of targets and specificity of the RNA tools as well as their tissue-specific and regulatable expression. We discuss analogies and differences between regulatory RNA therapy and classical gene therapy, since recent breakthroughs in vector technology are of importance for both. Recent years have witnessed parallel progress in the fields of gene-based and regulatory RNA-based therapies that are likely to significantly expand the cardiovascular therapeutic repertoire within the next decade.

Poller, Wolfgang; Hajjar, Roger; Schultheiss, Heinz-Peter; Fechner, Henry

2010-01-01

180

Hydrophobic chitosan sponges modified by aluminum monostearate and dehydrothermal treatment as sustained drug delivery system.  

PubMed

The aim of this study is to develop hydrophobic chitosan sponges by using novel simple preparation technique in which hydrophobicity of chitosan was modified by aluminum monostearate (Alst) and dehydrothermal treatment (DHT). Alst was able to dissociate and to cleave stearate ion in 2% w/v lactic acid. Composite dispersion of chitosan and Alst (CLA) could be easily prepared by simple mixing at room temperature. The pH value of the CLA dispersions and particle size of the chitosan-Alst complex in the system comprising low chitosan concentration significantly increased by mixing time. The dispersions were further fabricated into sponges by using lyophilization technique and DHT. FT-IR spectra analysis indicated amidation between amino group of chitosan and carboxyl group of stearate side chain after DHT. Contact angle measurement was applied to evaluate hydrophilic/hydrophobic properties of the prepared sponges. Swelling behavior of the sponges was investigated in three different medium namely acetate buffer (pH4.0), phosphate buffer (pH7.4) and carbonate buffer (pH10.0). Drug release study was conducted in phosphate buffer pH7.4 at 37°C by using asiaticoside as a model drug. Contact angle measurement revealed that addition of Alst and DHT enhanced the hydrophobicity of the materials. Swelling of the sponges decreased as Alst amount increased. Swelling behavior of the sponges was coincident with the release of asiaticoside in which the sponge containing higher Alst amount apparently exhibited the sustained release character. Release of asiaticoside from CLA sponges fitted well with first-order kinetic and the exponent value (n) in power law model indicated that the main release mechanism was Fickian diffusion. From this study, we found the potential of the prepared hydrophobic chitosan sponges for further application as drug-sustained-release, porous wound dressing. PMID:25063173

Yodkhum, Kotchamon; Phaechamud, Thawatchai

2014-09-01

181

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

PubMed

Microbubbles triggered with localized ultrasound (US) can improve tumor drug delivery and retention. Termed US-stimulated drug delivery, this strategy was applied to head and neck cancer (HNC) in a post-surgical tumor resection model. Luciferase-positive HNC squamous cell carcinoma (SCC) was implanted in the flanks of nude athymic mice (N = 24) that underwent various degrees of surgical tumor resection (0%, 50% or 100%). After surgery, animals received adjuvant therapy with cetuximab-IRDye alone, or cetuximab-IRDye in combination with US-stimulated drug delivery or saline injections (control) on days 4, 7 and 10. Tumor drug delivery was assessed on days 0, 4, 7, 10, 14 and 17 with an in vivo fluorescence imaging system, and tumor viability was evaluated at the same times with in vivo bioluminescence imaging. Tumor caliper measurements occurred two times per week for 24 d. Optical imaging revealed that in the 50% tumor resection group, US-stimulated drug delivery resulted in a significant increase in cetuximab delivery compared with administration of drug alone on day 10 (day of peak fluorescence) (p = 0.03). Tumor viability decreased in all groups that received cetuximab-IRDye in combination with US-stimulated drug delivery, compared with the group that received only the drug. After various degrees of surgical resection, this novel study reports positive improvements in drug uptake in the residual cancer cells when drug delivery is stimulated with US. PMID:24412168

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

2014-04-01

182

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.

Franca, Jucara Ribeiro; Foureaux, Giselle; Fuscaldi, Leonardo Lima; Ribeiro, Tatiana Gomes; Rodrigues, Livia Bomfim; Bravo, Renata; Castilho, Rachel Oliveira; Yoshida, Maria Irene; Cardoso, Valbert Nascimento; Fernandes, Simone Odilia; Cronemberger, Sebastiao; Ferreira, Anderson Jose; Faraco, Andre Augusto Gomes

2014-01-01

183

Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.  

PubMed

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

184

Selective Delivery of a Therapeutic Gene for Treatment of Head and Neck Squamous Cell Carcinoma Using Human Neural Stem Cells  

PubMed Central

Objectives Based on studies of the extensive tropism of neural stem cells (NSCs) toward malignant brain tumor, we hypothesized that NSCs could also target head and neck squamous cell carcinoma (HNSCC) and could be used as a cellular therapeutic delivery system. Methods To apply this strategy to the treatment of HNSCC, we used a human NSC line expressing cytosine deaminase (HB1.F3-CD), an enzyme that converts 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), an anticancer agent. HB1. F3-CD in combination with 5-FC were cocultured with the HNSCC (SNU-1041) to examine the cytotoxicity on target tumor cells in vitro. For in vivo studies, an HNSCC mouse model was created by subcutaneous implantation of human HNSCC cells into athymic nude mice. HB1.F3-CD cells were injected into mice using tumoral, peritumoral, or intravenous injections, followed by systemic 5-FC administration. Results In vitro, the HB1.F3-CD cells significantly inhibited the growth of an HNSCC cell line in the presence of the 5-FC. Independent of the method of injection, the HB1.F3-CD cells migrated to the HNSCC tumor, causing a significant reduction in tumor volume. In comparison to 5-FU administration, HB1.F3-CD cell injection followed by 5-FC administration reduced systemic toxicity, but achieved the same level of therapeutic efficacy. Conclusion Transplantation of human NSCs that express the suicide enzyme cytosine deaminase combined with systemic administration of the prodrug 5-FC may be an effective regimen for the treatment of HNSCC.

Kim, Seung U; Song, Jae-Jun; Cho, Chang Gun; Park, Seok-Won

2013-01-01

185

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

186

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

187

Noninvasive drug delivery  

Microsoft Academic Search

Advances in biopharmaceutical technology have spawned new drug delivery devices and mechanisms. Noninvasive methods, including\\u000a iontophoresis and transmucosal drug delivery, have improved treatment of certain patient population. Their use is discussed\\u000a in the following paper.

Ruth Zimmer; Michael A. Ashburn

2001-01-01

188

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

PubMed

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 strategies to control the irritation potential of salicylic acid formulations and have focused on hydroalcoholic solutions used in acne wipes. One strategy is to control the penetration of SA into the skin. Penetration of the drug into various layers of skin, i.e., epidermis, dermis, and receptor fluid, was measured using a modified Franz in vitro diffusion method after various exposure times up to 24 hours. A polyurethane polymer (polyolprepolymer-15) was found to be an effective agent in controlling delivery of SA. In a dose-dependent fashion it targeted delivery of more SA to the epidermis as compared to penetration through the skin into the receptor fluid. It also reduced the rapid rate of permeation of a large dose of SA through the skin in the first few hours of exposure. A second strategy that proved successful was incorporation of known mild nonionic surfactants like isoceteth-20. These surfactants cleanse the skin, yet due to their inherent mildness (because of their reduced critical micelle concentration and monomer concentration), keep the barrier intact. Also, they reduce the rate of salicylic acid penetration, presumably through micellar entrapment (either in solution or on the skin surface after the alcohol evaporates). Cumulative irritation studies showed that targeting delivery of SA to the epidermis and reducing the rapid early rate of penetration of large amounts of drug through the skin resulted in a reduced irritation potential. In vivo irritation studies also showed that the surfactant system is the most important factor controlling irritancy. SA delivery is secondary, as formulations with less SA content reduced the rate of delivery to the receptor and yet were some of the most irritating formulations tested, presumably due to the action of the specific anionic surfactant on the barrier. Alcohol content also did not appreciably affect irritation and SA delivery; formulations with considerably lower alcohol content but containing anionic versus nonionic surfactant systems exhibited considerably higher irritancy. Thus the surfactant type was again the predominant factor in those studies, although arguably alcohol plays some role (solubilization of SA). Results showed that both polymers and mild surfactants work in concert to provide the optimal formulation benefits of targeted delivery and reduced irritation. Synergistic relationships among hydroalcoholic formulation components will be discussed along with the mechanisms likely involved in controlling delivery of SA to skin. PMID:15037921

Rhein, Linda; Chaudhuri, Bhaskar; Jivani, Nur; Fares, Hani; Davis, Adrian

2004-01-01

189

A Highly Accurate Technique for the Treatment of Flow Equations at the Polar Axis in Cylindrical Coordinates using Series Expansions. Appendix A  

NASA Technical Reports Server (NTRS)

Numerical methods for solving the flow equations in cylindrical or spherical coordinates should be able to capture the behavior of the exact solution near the regions where the particular form of the governing equations is singular. In this work we focus on the treatment of these numerical singularities for finite-differences methods by reinterpreting the regularity conditions developed in the context of pseudo-spectral methods. A generally applicable numerical method for treating the singularities present at the polar axis, when nonaxisymmetric flows are solved in cylindrical, coordinates using highly accurate finite differences schemes (e.g., Pade schemes) on non-staggered grids, is presented. Governing equations for the flow at the polar axis are derived using series expansions near r=0. The only information needed to calculate the coefficients in these equations are the values of the flow variables and their radial derivatives at the previous iteration (or time) level. These derivatives, which are multi-valued at the polar axis, are calculated without dropping the accuracy of the numerical method using a mapping of the flow domain from (0,R)*(0,2pi) to (-R,R)*(0,pi), where R is the radius of the computational domain. This allows the radial derivatives to be evaluated using high-order differencing schemes (e.g., compact schemes) at points located on the polar axis. The proposed technique is illustrated by results from simulations of laminar-forced jets and turbulent compressible jets using large eddy simulation (LES) methods. In term of the general robustness of the numerical method and smoothness of the solution close to the polar axis, the present results compare very favorably to similar calculations in which the equations are solved in Cartesian coordinates at the polar axis, or in which the singularity is removed by employing a staggered mesh in the radial direction without a mesh point at r=0, following the method proposed recently by Mohseni and Colonius (1). Extension of the method described here for incompressible flows or for any other set of equations that are solved on a non-staggered mesh in cylindrical or spherical coordinates with finite-differences schemes of various level of accuracy is immediate.

Constantinescu, George S.; Lele, S. K.

2001-01-01

190

Drug delivery systems.  

PubMed

New and emerging drug delivery systems for traditional drugs and the products of biotechnology are discussed, and the role of the pharmacist in ensuring the appropriate use of these systems is outlined. Advantages of advanced drug delivery systems over traditional systems are the ability to deliver a drug more selectively to a specific site; easier, more accurate, less frequent dosing; decreased variability in systemic drug concentrations; absorption that is more consistent with the site and mechanism of action; and reductions in toxic metabolites. Four basic strategies govern the mechanisms of advanced drug delivery: physical, chemical, biological, and mechanical. Oral drug delivery systems use natural and synthetic polymers to deliver the product to a specific region in the gastrointestinal tract in a timely manner that minimizes adverse effects and increases drug efficacy. Innovations in injectable and implantable delivery systems include emulsions, particulate delivery systems, micromolecular products and macromolecular drug adducts, and enzymatic-controlled delivery. Options for noninvasive drug delivery include the transdermal, respiratory, intranasal, ophthalmic, lymphatic, rectal, intravaginal, and intrauterine routes as well as topical application. Rapid growth is projected in the drug delivery systems market worldwide in the next five years. Genetic engineering has mandated the development of new strategies to deliver biotechnologically derived protein and peptide drugs and chemoimmunoconjugates. The role of the pharmacist in the era of advanced drug delivery systems will be broad based, including administering drugs, compounding, calculating dosages based on pharmacokinetic and pharmacodynamic monitoring, counseling, and research. The advent of advanced drug delivery systems offers pharmacists a new opportunity to assume an active role in patient care. PMID:1772110

Robinson, D H; Mauger, J W

1991-10-01

191

IL12 Plasmid Delivery by in Vivo Electroporation for the Successful Treatment of Established Subcutaneous B16.F10 Melanoma  

Microsoft Academic Search

Interleukin-12 (IL-12) has been used in numerous immunotherapy protocols against melanoma. However, delivery of IL-12 in the form of recombinant protein can result in severe toxicity, and gene therapy has had limited success against B16.F10 murine melanoma. The purpose of this study was to examine the effectiveness of in vivo electroporation for the delivery of plasmid DNA encoding IL-12 as

M. Lee Lucas; Loree Heller; Domenico Coppola; Richard Heller

2002-01-01

192

Oral delivery of oil-based formulation for a novel synthetic cationic peptide of GnRH (gonadotropin-releasing hormone) antagonist for prostate cancer treatment.  

PubMed

LXT-101, a cationic peptide is a novel antagonist of gonadotropin-releasing hormone (GnRH) for prostate cancer treatment. However, effective delivery of peptide drugs into the body by the oral route remains a major challenge due to their origin properties with high molecular weights, strong polarity and low stability in the gastrointestinal (GI) tract. In this study, we have developed a novel oral delivery of oil-based formulation in which therapeutic peptide LXT-101 are solubilized in oils and with this solution as oil phase, an optimum formulation of self-microemulsifying drug delivery system (SMEDDS) was developed. The peptide stability with the SMEDDS formulation in artificial gastric and intestinal fluid was tested in vitro. On the other hand, the testosterone level and plasma concentration of LXT-101 in rats after oral administration of the SMEDDS formulation were investigated in vivo. The data in vitro indicated that LXT-101 in the SMEDDS formulation was stable over 8 h in artificial gastric and intestinal fluid. LXT-101 can be absorbed in vivo and suppression of testosterone maintained in castration level within 12 h can be achieved effectively after SMEDDS formulation administered orally at a dose of 3.5 mg/kg. The approach can provide a potential way for delivery peptides by oral. PMID:23623791

Zhang, Guiying; Wang, Tao; Gao, Lijun; Quan, Dongqin

2013-06-25

193

In Patients with Peptic Ulcer Disease, What Is the Most Accurate Diagnostic Test to Determine the Presence of Helicobacter pylori Prior to Treatment?  

Microsoft Academic Search

INTRODUCTION: Helicobacter Pylori is a common bacteria found in the stomach that can cause ulcers and more rarely gastric cancer. There are multiple diagnostic tests that are currently available to detect this microorganism possibly making it difficult for providers to choose the most accurate or inexpensive test. It is important to diagnosis H. pylori in symptomatic patients due to the

Jason R. Kwiatkowski

2009-01-01

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.

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

2014-01-01

195

Motivational Enhancement Therapy Coupled with Cognitive Behavioral Therapy versus Brief Advice; A Randomized Trial for Treatment of Hazardous Substance Use in Pregnancy and After Delivery  

PubMed Central

Objective To compare the efficacy of motivational enhancement therapy coupled with cognitive behavioral therapy (MET-CBT) to brief advice for treatment of substance use in pregnancy. Method This was a randomized, parallel, controlled trial that was yoked to prenatal care and delivered at hospital outpatient clinics. We enrolled 168 substance using women who had not yet completed an estimated 28 weeks of pregnancy. Obstetrical clinicians provided brief advice and study nurses administered manualized MET-CBT. The primary outcome was percentage of days in the prior 28 days, that alcohol and/or drugs were used immediately before and three months post delivery. Results There were no significant differences across groups in terms of self-reported percentage of days that drugs or alcohol were used prior to and three months post delivery. Biological measures showed similar results. There was a trend (p=0.08) for lower risk of preterm birth among those who received MET-CBT. Conclusions The tested interventions had similar therapeutic effects. Hence, both treatments may be suitable for pregnant substance users, depending on the population, setting, and provider availability. Interventions that are intensified after delivery may decrease postpartum ‘rebound’ effects in substance misuse.

Yonkers, Kimberly A.; Forray, Ariadna; Howell, Heather B.; Gotman, Nathan; Kershaw, Trace; Rounsaville, Bruce J.; Carroll, Kathleen M.

2012-01-01

196

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

197

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging  

Microsoft Academic Search

Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be

Sonu Bhaskar; Furong Tian; Tobias Stoeger; Wolfgang Kreyling; Jesús M de la Fuente; Valeria Grazú; Paul Borm; Giovani Estrada; Vasilis Ntziachristos; Daniel Razansky

2010-01-01

198

A silk hydrogel-based delivery system of bone morphogenetic protein for the treatment of large bone defects.  

PubMed

The use of tissue grafting for the repair of large bone defects has numerous limitations including donor site morbidity and the risk of disease transmission. These limitations have prompted research efforts to investigate the effects of combining biomaterial scaffolds with biochemical cues to augment bone repair. The goal of this study was to use a critically-sized rat femoral segmental defect model to investigate the efficacy of a delivery system consisting of an electrospun polycaprolactone (PCL) nanofiber mesh tube with a silk fibroin hydrogel for local recombinant bone morphogenetic protein 2 (BMP-2) delivery. Bilateral 8 mm segmental femoral defects were formed in 13-week-old Sprague Dawley rats. Perforated electrospun PCL nanofiber mesh tubes were fitted into the adjacent native bone such that the lumen of the tubes contained the defect (Kolambkar et al., 2011b). Silk hydrogels with or without BMP-2 were injected into the defect. Bone regeneration was longitudinally assessed using 2D X-ray radiography and 3D microcomputed topography (?CT). Following sacrifice at 12 weeks after surgery, the extracted femurs were either subjected to biomechanical testing or assigned for histology. The results demonstrated that silk was an effective carrier for BMP-2. Compared to the delivery system without BMP-2, the delivery system that contained BMP-2 resulted in more bone formation (p<0.05) at 4, 8, 12 weeks after surgery. Biomechanical properties were also significantly improved in the presence of BMP-2 (p<0.05) and were comparable to age-matched intact femurs. Histological evaluation of the defect region indicated that the silk hydrogel has been completely degraded by the end of the study. Based on these results, we conclude that a BMP-2 delivery system consisting of an electrospun PCL nanofiber mesh tube with a silk hydrogel presents an effective strategy for functional repair of large bone defects. PMID:22658161

Diab, Tamim; Pritchard, Eleanor M; Uhrig, Brent A; Boerckel, Joel D; Kaplan, David L; Guldberg, Robert E

2012-07-01

199

Magnetic Resonance Imaging-Guided Delivery of Adeno-Associated Virus Type 2 to the Primate Brain for the Treatment of Lysosomal Storage Disorders  

PubMed Central

Abstract Gene replacement therapy for the neurological deficits caused by lysosomal storage disorders, such as in Niemann-Pick disease type A, will require widespread expression of efficacious levels of acid sphingomyelinase (ASM) in the infant human brain. At present there is no treatment available for this devastating pediatric condition. This is partly because of inherent constraints associated with the efficient delivery of therapeutic agents into the CNS of higher order models. In this study we used an adeno-associated virus type 2 (AAV2) vector encoding human acid sphingomyelinase tagged with a viral hemagglutinin epitope (AAV2-hASM-HA) to transduce highly interconnected CNS regions such as the brainstem and thalamus. On the basis of our data showing global cortical expression of a secreted reporter after thalamic delivery in nonhuman primates (NHPs), we set out to investigate whether such widespread expression could be enhanced after brainstem infusion. To maximize delivery of the therapeutic transgene throughout the CNS, we combined a single brainstem infusion with bilateral thalamic infusions in naive NHPs. We found that enzymatic augmentation in brainstem, thalamic, cortical, as well subcortical areas provided convincing evidence that much of the large NHP brain can be transduced with as few as three injection sites.

Salegio, E. Aguilar; Kells, A.P.; Richardson, R.M.; Hadaczek, P.; Forsayeth, J.; Bringas, J.; Sardi, S.P.; Passini, M.A.; Shihabuddin, L.S.; Cheng, S.H.; Fiandaca, M.S.

2010-01-01

200

Estimation of skin target site acyclovir concentrations following controlled (trans)dermal drug delivery in topical and systemic treatment of cutaneous HSV-1 infections in hairless mice.  

PubMed

The use of controlled transdermal delivery of acyclovir (ACV) in the treatment of cutaneous herpes simplex virus type 1 infections in hairless mice was investigated. Using an in vivo animal model (A. Gonsho, et al. Int. J. Pharm. 65:183-194 (1990)) made it possible to quantify both, the topical and the systemic antiviral efficacy of ACV transdermal patches as a function of the drug delivery rate of the patches. Drug delivery rates required to attain systemic efficacy were found to be higher than the rates required to attain the same magnitude of topical efficacy. The ACV concentrations in the basal cell layer of the epidermis for 50% topical efficacy and 50% systemic efficacy were estimated. The basal epidermis layer was considered to be the site of antiviral drug activity (skin target site). Systemic plasma levels were obtained from pharmacokinetic studies and were used to estimate the ACV concentration achieved systemically in the basal epidermis layer. A computational model for drug permeation across skin was employed to estimate the ACV concentration achieved topically in the basal epidermis layer. Equal topical and systemic efficacies were found to correspond to equal drug concentrations at the site of antiviral activity. The length of the effective diffusion pathway of drug molecules in the dermis prior to entering the blood circulation was assumed to be approximately equal to 1/20 of the anatomical dermis thickness because of dermis vascularization. PMID:7937545

Imanidis, G; Song, W Q; Lee, P H; Su, M H; Kern, E R; Higuchi, W I

1994-07-01

201

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

2014-04-01

202

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

203

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

204

Targeting sphingosine kinase 1 (SphK1) and apoptosis by colon-specific delivery formula of resveratrol in treatment of experimental ulcerative colitis in rats.  

PubMed

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder (IBD) that has an elevated risk of developing into colon cancer. In trials to develop new therapeutic alternatives for UC, it is important to fulfill modifying effects on pathogenic targets and to reach the colon in a high concentration. Thus, the current work has investigated a colon-specific delivery formula of resveratrol in targeting sphingosine kinase 1 (SphK1) and apoptotic pathways to control pathogenesis and its progression to any expected neoplasm. This work was conducted on 40 Wister albino rats equally divided into 4 groups where group I served as the normal control group. The untreated oxazolone-induced colitis in group II exhibited significant increase in SphK1 activity as well as activity of both myeloperoxidase (MPO) and caspase-3 with concomitant mild DNA fragmentation in colonic tissue. Colonic SphK1 activity showed significant positive correlation with the disease activity index (DAI) and histopathological score in this group. Comparable with treatment by the native resveratrol formula, nRes (group III), treatment by the colon-specific delivery resveratrol formula, cRes (group IV) caused significant decrease in the activity of SphK1 and MPO with massive DNA fragmentation in colonic tissue and non significant change in caspase-3 activity. The lowest DAI and histopathological score have been recorded in the group treated by the colon-specific delivery resveratrol formula. In conclusion, the anti-inflammatory and apoptotic effects of resveratrol could be attributed to its inhibitory effect on sphingosine kinase 1 (SphK1) providing a useful therapeutic tool to break the link between inflammation and carcinogenesis risk in ulcerative colitis. PMID:24055189

Abdin, Amany A

2013-10-15

205

Assessing second echelon lymph nodes during sentinel lymph node biopsy: can we have more accurate axillary treatment for breast cancer patients?  

PubMed

Sentinel lymph node biopsy (SLNB) is the standard treatment for breast cancer patients with clinically negative axilla. For patients with positive sentinel lymph nodes, axillary lymph node dissection (ALND) was required. However, approximately a half of the SLNs-positive patients were found to have clear axillary lymph nodes after ALND, indicating that they had received unnecessary ALND without therapeutic benefit. Therefore, we propose a hypothesis for solution of this clinical problem. We defined the second echelon lymph nodes (SELNs) as those nodes receiving lymphatic drainage directly from the SLNs. For patients with positive-SLNs, SELNs can be biopsy and assessed. If SELNs are negative, no more ALND was needed in these patients even if their SLNs are positive. If our hypothesis were confirmed to be true, we can tailored our axillary treatment to more breast cancer patients, avoiding unnecessary ALND and its complications. PMID:21908107

Chen, Kai; Jia, Weijuan; Rao, Nanyan; Deng, Heran; Jin, Liang; Song, Erwei; Su, Fengxi

2011-12-01

206

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

207

Nanoscale Drug Delivery and Hyperthermia: The Materials Design and Preclinical and Clinical Testing of Low Temperature-Sensitive Liposomes Used in Combination with Mild Hyperthermia in the Treatment of Local Cancer  

PubMed Central

The overall objective of liposomal drug delivery is to selectively target drug delivery to diseased tissue, while minimizing drug delivery to critical normal tissues. The purpose of this review is to provide an overview of temperature-sensitive liposomes in general and the Low Temperature-Sensitive Liposome (LTSL) in particular. We give a brief description of the material design of LTSL and highlight the likely mechanism behind temperature-triggered drug release. A complete review of the progress and results of the latest preclinical and clinical studies that demonstrate enhanced drug delivery with the combined treatment of hyperthermia and liposomes is provided as well as a clinical perspective on cancers that would benefit from hyperthermia as an adjuvant treatment for temperature-triggered chemotherapeutics. This review discusses the ideas, goals, and processes behind temperature-sensitive liposome development in the laboratory to the current use in preclinical and clinical settings.

Landon, Chelsea D.; Park, Ji-Young; Needham, David; Dewhirst, Mark W.

2012-01-01

208

An acetylated polysaccharide-PTFE membrane-covered stent for the delivery of gemcitabine for treatment of gastrointestinal cancer and related stenosis.  

PubMed

Gemcitabine (Gem) eluting metal stents were prepared for potential application as drug delivery systems for localized treatment of malignant tumors. Pullulan, a natural polysaccharide, was chemically acetylated (pullulan acetate; PA) by different degrees (1.18, 1.71, and 2.10 acetyl groups per glucose unit of pullulan), layered on polytetrafluoroethylene (PTFE), and applied as part of a Gem-loaded controlled-release membrane for drug-eluting non-vascular stents. PA with a higher degree of acetylation had greater drug-loading capacity with more extended release of Gem over 30 days. The released Gem accumulated in CT-26 colon cancer without systemic exposure inducing total regression of tumors. The long-term biological activity of the released Gem and apoptosis of tumor tissues following localized delivery were confirmed by annexin V binding assays and histology. The controlled release of Gem from PA-PTFE covered drug-eluting stents (DES) may increase the patency of these stents for the treatment of malignant gastrointestinal cancer as well as cancer-related stenosis. PMID:21334742

Moon, Sumi; Yang, Su-Geun; Na, Kun

2011-05-01

209

Co-delivery of doxorubicin and paclitaxel by PEG-polypeptide nanovehicle for the treatment of non-small cell lung cancer.  

PubMed

Despite progress, combination therapy of different functional drugs to increase the efficiency of anticancer treatment still remains challenges. An amphiphilic methoxy poly(ethylene glycol)-b-poly(l-glutamic acid)-b-poly(l-lysine) triblock copolymer decorated with deoxycholate (mPEsG-b-PLG-b-PLL/DOCA) was synthesized and developed as a nanovehicle for the co-delivery of anticancer drugs: doxorubicin (DOX) and paclitaxel (PTX). The amphiphilic copolymer spontaneously self-assembled into micellar-type nanoparticles in aqueous solutions and the blank nanoparticles possessed excellent stability. Three different domains of the copolymer performed distinct functions: PEG outer corona provided prolonged circulation, middle biodegradable and hydrophilic PLG shell was designed for DOX loading through electrostatic interactions, and hydrophobic deoxycholate modified PLL served as the container for PTX. In vitro cytotoxicity assays against A549 human lung adenocarcinoma cell line demonstrated that the DOX + PTX co-delivered nanoparticles (Co-NPs) exhibited synergistic effect in inducing cancer cell apoptosis. Ex vivo DOX fluorescence imaging revealed that Co-NPs had highly efficient targeting and accumulation at the implanted site of A549 xenograft tumor in vivo. Co-NPs exhibited significantly higher antitumor efficiency in reducing tumor size compared to free drug combination or single drug-loaded nanoparticles, while no obvious side effects were observed during the treatment, indicating this co-delivery system with different functional antitumor drugs provides the clinical potential in cancer therapy. PMID:24794923

Lv, Shixian; Tang, Zhaohui; Li, Mingqiang; Lin, Jian; Song, Wantong; Liu, Huaiyu; Huang, Yubin; Zhang, Yuanyuan; Chen, Xuesi

2014-07-01

210

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

211

Novel treatment of coronary artery fistulae concealing severe coronary artery lesion: using thrombus aspiration catheter as a delivery guide  

PubMed Central

In this case report, we present the occlusion of multiple coronary artery fistulae originating from proximal left anterior descending (LAD) and right sinus valsavla and empting to the pulmonary artery at the same place. We occluded LAD fistulae by using thrombus aspiration catheter as a delivery guide. To the best of our knowlege, this is the first case of occlusion of coronary fistulae with the help of thrombus aspiration catheter. Our experience may suggest that thrombus aspiration catheters can be used in treating coronary artery fistulae with difficult anotomy.

Korkmaz, Levent; Acar, Zeydin; Dursun, Ihsan; Akyuz, Ali R?za; Korkmaz, Ayca Ata

2014-01-01

212

Advances in Targeting Drug Delivery to Glomerular Mesangial Cells by Long Circulating Cationic Liposomes for the Treatment of Glomerulonephritis  

Microsoft Academic Search

Purpose  Newly designed polyethylene glycol (PEG)-modified cationic liposomes, containing a novel cationic lipid TRX-20 (3,5-dipentadecyloxybenzamidine\\u000a hydrochloride), bind specifically to cultured human mesangial cells, and not to endothelial cells. In this study, we investigated\\u000a targeting the delivery of PEG-modified liposomes containing TRX-20 (TRX-liposomes) to mesangial cells and evaluated their\\u000a pharmacokinetic behavior in a rat experimental glomerulonephritis model, using prednisolone phosphate (PSLP) as

Katsumi Morimoto; Masayo Kondo; Kazuo Kawahara; Hideto Ushijima; Yasuhiko Tomino; Masaharu Miyajima; Junji Kimura

2007-01-01

213

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

214

Well-defined, size-tunable, multi-functional micelles for efficient paclitaxel delivery for cancer treatment  

PubMed Central

We have developed a well-defined and biocompatible amphiphilic telodendrimer system (PEG-b-dendritic oligo-cholic acid) which can self-assemble into multifunctional micelles in aqueous solution for efficient delivery of hydrophobic drugs such as paclitaxel. In this telodendrimer system, cholic acid is essential for the formation of stable micelles with high drug loading capacity, owing to its facial amphiphilicity. A series of telodendrimers with variable length of PEG chain and number of cholic acid in the dendritic blocks were synthesized. The structure and molecular weight of each of these telodendrimers were characterized, and their critical micellization concentration (CMC), drug-loading properties, particle sizes and cytotoxicity were examined and evaluated for further optimization for anticancer drug delivery. The sizes of the micelles, with and without paclitaxel loading, could be tuned from 11.5 to 21 nm and from 15 to 141 nm, respectively. Optical imaging studies in xenograft models demonstrated preferential uptakes of the smaller paclitaxel-loaded micelles (17–60 nm) by the tumor, and the larger micelles (150 nm) by the liver and lung. The toxicity and anti-tumor efficacy profiles of these paclitaxel-loaded micelles in xenograft models were found to be superior to those of Taxol® and Abraxane®.

Luo, Juntao; Xiao, Kai; Li, Yuanpei; Lee, Joyce S.; Shi, Lifang; Tan, Yih-Horng; Xing, Li; Cheng, R. Holland; Liu, Gang-Yu; Lam, Kit S.

2010-01-01

215

Tumor-targeted Chlorotoxin-coupled Nanoparticles for Nucleic Acid Delivery to Glioblastoma Cells: A Promising System for Glioblastoma Treatment  

PubMed Central

The present work aimed at the development and application of a lipid-based nanocarrier for targeted delivery of nucleic acids to glioblastoma (GBM). For this purpose, chlorotoxin (CTX), a peptide reported to bind selectively to glioma cells while showing no affinity for non-neoplastic cells, was covalently coupled to liposomes encapsulating antisense oligonucleotides (asOs) or small interfering RNAs (siRNAs). The resulting targeted nanoparticles, designated CTX-coupled stable nucleic acid lipid particles (SNALPs), exhibited excellent features for in vivo application, namely small size (<180?nm) and neutral surface charge. Cellular association and internalization studies revealed that attachment of CTX onto the liposomal surface enhanced particle internalization into glioma cells, whereas no significant internalization was observed in noncancer cells. Moreover, nanoparticle-mediated miR-21 silencing in U87 human GBM and GL261 mouse glioma cells resulted in increased levels of the tumor suppressors PTEN and PDCD4, caspase 3/7 activation and decreased tumor cell proliferation. Preliminary in vivo studies revealed that CTX enhances particle internalization into established intracranial tumors. Overall, our results indicate that the developed targeted nanoparticles represent a valuable tool for targeted nucleic acid delivery to cancer cells. Combined with a drug-based therapy, nanoparticle-mediated miR-21 silencing constitutes a promising multimodal therapeutic approach towards GBM.

Costa, Pedro M; Cardoso, Ana L; Mendonca, Liliana S; Serani, Angelo; Custodia, Carlos; Conceicao, Mariana; Simoes, Sergio; Moreira, Joao N; Pereira de Almeida, Luis; Pedroso de Lima, Maria C

2013-01-01

216

Transcutaneous electroporation mediated delivery of doxepin-HPCD complex: A sustained release approach for treatment of postherpetic neuralgia  

PubMed Central

The electroporation mediated transdermal delivery (Protocol - 120V, 10ms, 30pulses at 1Hz with post pulse waiting period of 20min) of doxepin using pure drug solution (PDS) and doxepin-hydroxypropyl-?-cyclodextrin (HPCD) complex solution (CDS) was studied using porcine epidermis model. The stoichiometry of drug-HPCD inclusion complex was determined by differential scanning calorimetry (DSC). The amount of doxepin retained in the epidermis following electroporation did not differ significantly between PDS and CDS. When the drug loaded epidermis was subjected to “Release studies”, doxepin release attained a plateau within ~2.5 days in case of PDS, whereas in case of CDS, doxepin release was prolonged up to 5 days. Mechanistic studies across the nonbiological barriers demonstrated that the slow dissociation of complex was responsible for sustained release of drug from the epidermis. Pharmacodynamic studies were carried out by electroporation mediated delivery of CDS and PDS in hairless rats. The analgesic effect of doxepin was prolonged in case of CDS as compared to PDS.

Sammeta, Srinivasa M.; Vaka, Siva Ram K.; Murthy, S. Narasimha

2009-01-01

217

Molecular Bacterial Load Assay, a Culture-Free Biomarker for Rapid and Accurate Quantification of Sputum Mycobacterium tuberculosis Bacillary Load during Treatment ? #  

PubMed Central

A molecular assay to quantify Mycobacterium tuberculosis is described. In vitro, 98% (n = 96) of sputum samples with a known number of bacilli (107 to 102 bacilli) could be enumerated within 0.5 log10. In comparison to culture, the molecular bacterial load (MBL) assay is unaffected by other microorganisms present in the sample, results are obtained more quickly (within 24 h) and are seldom inhibited (0.7% samples), and the MBL assay critically shows the same biphasic decline as observed longitudinally during treatment. As a biomarker of treatment response, the MBL assay responds rapidly, with a mean decline in bacterial load for 111 subjects of 0.99 log10 (95% confidence interval [95% CI], 0.81 to 1.17) after 3 days of chemotherapy. There was a significant association between the rate of bacterial decline during the same 3 days and bacilli ml?1 sputum at day 0 (linear regression, P = 0.0003) and a 3.62 increased odds ratio of relapse for every 1 log10 increase in pretreatment bacterial load (95% CI, 1.53 to 8.59).

Honeyborne, Isobella; McHugh, Timothy D.; Phillips, Patrick P. J.; Bannoo, Selina; Bateson, Anna; Carroll, Nora; Perrin, Felicity M.; Ronacher, Katharina; Wright, Laura; van Helden, Paul D.; Walzl, Gerhard; Gillespie, Stephen H.

2011-01-01

218

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

219

Disposable Device for Delivery of Accurate and Filtered Liquid Samples.  

National Technical Information Service (NTIS)

The invention concerns an improved method and apparatus for providing laboratory or field samples of liquids. A disposable pipet tip having a very fine opening is detachably attached to the combination of a disposable syringe filter and a ratchetted, posi...

A. P. Murphy M. K. Price

1992-01-01

220

Grading More Accurately  

ERIC Educational Resources Information Center

Grades matter. College grading systems, however, are often ad hoc and prone to mistakes. This essay focuses on one factor that contributes to high-quality grading systems: grading accuracy (or "efficiency"). I proceed in several steps. First, I discuss the elements of "efficient" (i.e., accurate) grading. Next, I present analytical results…

Rom, Mark Carl

2011-01-01

221

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.

2014-01-01

222

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

223

Applying technology to the treatment of cannabis use disorder: comparing telephone versus Internet delivery using data from two completed trials.  

PubMed

Technology-based interventions such as those delivered by telephone or online may assist in removing significant barriers to treatment seeking for cannabis use disorder. Little research, however, has addressed differing technology-based treatments regarding their comparative effectiveness, and how user profiles may affect compliance and treatment satisfaction. This study addressed this issue by examining these factors in online (N=225) versus telephone (N=160) delivered interventions for cannabis use, using data obtained from two previously published randomized controlled trials conducted by the current authors. Several differences emerged including stronger treatment effects (medium to large effect sizes in the telephone study versus small effect sizes in the Web study) and lower dropout in the telephone intervention (38% vs. 46%). Additionally, around half of the telephone study participants sought concurrent treatment, compared with 2% of participants in the Web study. Demographics and predictors of treatment engagement, retention and satisfaction also varied between the studies. Findings indicate that both telephone and Web-based treatments can be effective in assisting cannabis users to quit or reduce their use; however, participant characteristics may have important implications for treatment preference and outcome, with those who elect telephone-based treatment experiencing stronger outcomes. Thus, participant preference may shape study populations, adherence, and outcome. PMID:24051076

Rooke, Sally E; Gates, Peter J; Norberg, Melissa M; Copeland, Jan

2014-01-01

224

A comparative evaluation of atrigel delivery system (10% doxycycline hyclate) Atridox with scaling and root planing and combination therapy in treatment of periodontitis: A clinical study  

PubMed Central

Background: Local delivery of antimicrobial has resulted in good clinical outcome along with scaling and root planing. The present study is carried out to evaluate and compare the efficacy of local delivery of 10% doxycycline hyclate in adjunct to scaling and root planing in the treatment of periodontitis. Materials and Methods: A randomized crossover split mouth design was performed, a total number of 130 sites from 4 patients, 63 sites from patients with aggressive periodontitis and 67 sites from chronic periodontitis patients were selected and divided into scaling and root planing (SRP) group, SRP and doxycycline group and doxycycline alone group. Clinical parameters viz. plaque index, modified gingival index, bleeding index, clinical attachment level (CAL), and sub gingival temperature were evaluated on day 0, 15th, 45th, and 90th day. CAL recording was performed only on day 0 and 90th day. Results: In 90 days study, all the three groups showed significant reduction in clinical parameters. But on comparison, SRP and doxycycline group showed better results than doxycycline alone group and SRP alone group. Conclusion: The results of this study demonstrated that doxycycline hyclate 10% gel (Atridox) is as effective as SRP in reducing the clinical signs of periodontitis.

Javali, Mukhatar Ahmed; Vandana, K. L.

2012-01-01

225

High rates of adherence and treatment success in a public and public-private HIV clinic in India: potential benefits of standardized national care delivery systems  

PubMed Central

Background The massive scale-up of antiretroviral treatment (ART) access worldwide has brought tremendous benefit to populations affected by HIV/AIDS. Optimising HIV care in countries with diverse medical systems is critical; however data on best practices for HIV healthcare delivery in resource-constrained settings are limited. This study aimed to understand patient characteristics and treatment outcomes from different HIV healthcare settings in Bangalore, India. Methods Participants from public, private and public-private HIV healthcare settings were recruited between 2007 and 2009 and were administered structured interviews by trained staff. Self-reported adherence was measured using the visual analogue scale to capture adherence over the past month, and a history of treatment interruptions (defined as having missed medications for more than 48 hours in the past three months). In addition, CD4 count and viral load (VL) were measured; genotyping for drug resistance-associated mutations was performed on those who were in virological failure (VL > 1000 copies/ml). Results A total of 471 individuals were included in the analysis (263 from the public facility, 149 from the public-private facility and 59 from the private center). Private facility patients were more likely to be male, with higher education levels and incomes. More participants reported ? 95% adherence among public and public-private groups compared to private participants (public 97%; private 88%; public-private 93%, p < 0.05). Treatment interruptions were lowest among public participants (1%, 10%, 5% respectively, p < 0.001). Although longer clinic waiting times were experienced by more public participants (48%, compared to private 27%, public-private 19%, p < 0.001), adherence barriers were highest among private (31%) compared with public (10%) and public-private (17%, p < 0.001) participants. Viral load was detectable in 13% public, 22% private and 9% public-private participants (p < 0.05) suggesting fewer treatment failures among public and public-private settings. Drug resistance mutations were found more frequently among private facility patients (20%) compared to those from the public (9%) or public-private facility (8%, p < 0.05). Conclusions Adherence and treatment success was significantly higher among patients from public and public-private settings compared with patients from private facilities. These results suggest a possible benefit of the standardized care delivery system established in public and public-private health facilities where counselling by a multi-disciplinary team of workers is integral to provision of ART. Strengthening and increasing public-private partnerships can enhance the success of national ART programs.

2011-01-01

226

Accurate monotone cubic interpolation  

NASA Technical Reports Server (NTRS)

Monotone piecewise cubic interpolants are simple and effective. They are generally third-order accurate, except near strict local extrema where accuracy degenerates to second-order due to the monotonicity constraint. Algorithms for piecewise cubic interpolants, which preserve monotonicity as well as uniform third and fourth-order accuracy are presented. The gain of accuracy is obtained by relaxing the monotonicity constraint in a geometric framework in which the median function plays a crucial role.

Huynh, Hung T.

1991-01-01

227

Accurate Finite Difference Algorithms  

NASA Technical Reports Server (NTRS)

Two families of finite difference algorithms for computational aeroacoustics are presented and compared. All of the algorithms are single step explicit methods, they have the same order of accuracy in both space and time, with examples up to eleventh order, and they have multidimensional extensions. One of the algorithm families has spectral like high resolution. Propagation with high order and high resolution algorithms can produce accurate results after O(10(exp 6)) periods of propagation with eight grid points per wavelength.

Goodrich, John W.

1996-01-01

228

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

229

Early Stage Treatment of Compartment Syndrome Using Polymer Sol-Gel Composite Growth Factor Delivery Wound Dressings.  

National Technical Information Service (NTIS)

Compartment syndrome (CS) as a result of blast or traumatic injury is a devastating problem in the battlefield. The ultimate goal of this study is to develop an integrated toolkit of novel, biodegradable wound dressing composites for early stage treatment...

C. Knabe H. Qu J. Kim P. Ducheyne S. Radin

2008-01-01

230

Intra-articular drug delivery from an optimized topical patch containing teriflunomide and lornoxicam for rheumatoid arthritis treatment: does the topical patch really enhance a local treatment?  

PubMed

Patients with rheumatoid arthritis (RA) often bear joint destruction and symptomatic pain. The aim of this work is to develop a compound transdermal patch containing teriflunomide (TEF) and lornoxicam (LOX) to transport these drugs across the skin with the isochronous permeation rates for RA therapy and investigate intra-articular delivery of TEF and LOX following transdermal patches applied topically. The salts of TEF and LOX with organic amines diethylamine (DEtA), triethylamine (TEtA), diethanolamine (DEA), triethanolamine (TEA) and N-(2'-hydroxy-ethanol)-piperdine (NP) were prepared to improve the skin permeation of the parent drug. The optimized patch formulation is obtained from a 3-factor, 2-level central composite design. After topical application of the optimized compound patch to only one knee joint in rabbit, intra-articular delivery of TEF and LOX on the application site was compared with that on the non-application site. Anti-inflammatory and analgesic effects of the optimized compound patch were evaluated using the adjuvant arthritis model and the pain model induced by acetic acid, respectively. The in vitro experiment results showed that the amine salts of TEF and LOX, especially TEF-TEtA and LOX-TEtA, enhanced the skin permeation of TEF and LOX from the transdermal patch system. The optimal formulation successfully displayed isochronous permeation rates for TEF and LOX across rabbit skin, and was defined with 5% of TEF-TEtA, 10% of LOX-TEtA and 15% of azone. The in vivo study showed that TEF and LOX from transdermal patches were transferred into skin, ligament and fat pad on the application site by direct diffusion and on the non-application site by the redistribution of systemic blood supply, while local absorption of TEF and LOX in synovial fluid originated from the systemic blood supply rather than direct diffusion. In the RA rat model, the results of swelling inhibition on primary arthritis of bilateral hind paws further confirmed the above-mentioned point. The optimal formulation displayed a double response on joint inflammation and symptomatic pain. In conclusion, although transdermal administration applied topically can provide a local enhanced drug delivery for the superficial joint tissues by direct diffusion, it seemed unlikely to do that for the deeper tissue synovial fluid. PMID:23567043

Xi, Honglei; Cun, Dongmei; Xiang, Rongwu; Guan, Yanli; Zhang, Yuxiu; Li, Yuanru; Fang, Liang

2013-07-10

231

Patient navigation for American Indians undergoing cancer treatment: utilization and impact on care delivery in a regional health care center  

PubMed Central

Purpose To assess patient navigation (PN) utilization and its impact on treatment interruptions and clinical trial enrollment among American Indian (AI) cancer patients. Methods Between February 2004 and September 2009, 332 AI cancer patients received PN services throughout cancer treatment. The PN program provided culturally-competent navigators to assist patients with navigating cancer therapy, obtaining medications, insurance issues, communicating with medical providers, and travel and lodging logistics. Data on utilization and trial enrollment were prospectively collected. Data for a historical control group of 70 AI patients who did not receive PN services were used to compare treatment interruptions among those undergoing PN during curative radiation therapy (subgroup of 123 patients). Results The median number of contacts with a navigator was 12 (range, 1-119). The median time spent with the navigator at first contact was 40 minutes (range 10-250 min.) and 15 min for subsequent contacts. Patients treated with radiation therapy with curative intent who underwent PN had fewer days of treatment interruption (mean, 1.7 days; 95% CI, 1.1-2.2 days) than historical controls who did not receive PN services (mean, 4.9 days; 95% CI, 2.9-6.9 days). Of the 332 patients, 72 (22%; 95% CI, 17-26%) were enrolled on a clinical treatment trial or cancer control protocol. Conclusions PN was associated with fewer treatment interruptions and relatively high rates of clinical trial enrollment among AI cancer patients compared to national reports.

Guadagnolo, B. Ashleigh; Boylan, Amy; Sargent, Michelle; Koop, David; Brunette, Deb; Kanekar, Shalini; Shortbull, Vanessa; Molloy, Kevin; Petereit, Daniel G.

2010-01-01

232

Development of poly(butylene succinate) microspheres for delivery of levodopa in the treatment of Parkinson's disease.  

PubMed

Parkinson's is a major neurodegenerative disorder that occurs due to loss of dopaminergic neurons in basal ganglia. Conventional therapy includes surgery that involves lot of risk and administration of levodopa which is accompanied by poor bioavailability, short half-life, and side effects. In the present study, poly(butylene succinate) (PBSu) microspheres-based drug delivery system to improve the bioavailability of the drug levodopa was evaluated for the first time. Biodegradable porous and smooth PBSu microspheres were prepared by double emulsion solvent evaporation technique (W/O/W) and the effect of solvent and surfactant was studied. The maximum encapsulation efficiency achieved was 53.93% and 62.28% for porous and smooth microspheres, respectively. In vitro drug release was studied in phosphate buffered saline and simulated CSF buffer of pH 7.4. Initially a burst effect followed by sustained release of drug was obtained for about 32 h and 159 h for porous and smooth microspheres, respectively. The release rate was higher in simulated CSF when compared with PBS, due to higher concentration of sodium ions and cations in simulated CSF. PMID:23401377

Mohanraj, Krithika; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

2013-07-01

233

A magnetic chitosan hydrogel for sustained and prolonged delivery of Bacillus Calmette-Guérin in the treatment of bladder cancer.  

PubMed

The aim of this study was to develop a magnetic thermosensitive hydrogel as intravesical Bacillus Calmette-Guérin (BCG) delivery system, which was formulated with chitosan (CS), ?-glycerophosphate (GP) and Fe3O4 magnetic nanoparticle (Fe3O4-MNP). The gelation time and magnetic response of the gel system were investigated. The morphology of the gel was displayed by scanning electron microscope. Frozen section examination was creatively employed for exhibiting the structure of the gel and determining its intravesical residence time. The antitumor effect and local immune activity of BCG loaded magnetic gel were evaluated. The flowing solution of CS/GP under room temperature could gelate rapidly at body temperature both in vitro and in vivo. The magnetic injectable hydrogels significantly prolonged intravesical BCG residence time under an applied magnetic field. In comparison to traditional BCG therapy for superficial bladder tumor, BCG delivered by the gel system induced a stronger Th1 immune response and revealed higher antitumor efficacy. PMID:24070571

Zhang, Dong; Sun, Peng; Li, Peng; Xue, Aibing; Zhang, Xiaokai; Zhang, Haiyang; Jin, Xunbo

2013-12-01

234

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

235

Microemulsion as a tool for the transdermal delivery of ondansetron for the treatment of chemotherapy induced nausea and vomiting.  

PubMed

The main objective of this study was to develop a microemulsion (ME) formulation for transdermal delivery of ondansetron for chemotherapy induced nausea and vomiting (CINV). For the formulation development oil was selected on the basis of drug solubility in it while the surfactants and co-surfactants (S(mix)) were screened on the basis of their capacity to solubilize the oil as well as their efficiency to provide the microemulsion area. The microemulsion existence ranges were defined through the construction of the pseudo-ternary phase diagram and various formulations were developed. Effect of surfactant and cosurfactant mass ratio (S(mix)) on the microemulsion formation and its permeation through excised rat skin was studied. A significant increase in permeability parameters such as steady-state flux (J(ss)), permeability coefficient (K(p)), and enhancement ratio (ER) was observed in ME. Formulation B4 which consisted of 0.5% (w/w) of ondansetron, 5% (w/w) of oleic acid, 30% (w/w) S(mix) (2:1, Tween 20 and PEG 400) and 64.5% (w/w) of distilled water showed the best permeability profile. The formulation B4 was subjected to various in vitro attributes and converted to microemulsion gel (OMG). In order to predict the efficacy, pharmacokinetic studies were performed and pharmacokinetic profile was compared with ondansetron conventional gel (OCG) and oral marketed syrup (ONDANZ). The absorption of ondansetron from OMG resulted in 6.03 fold increase in bioavailability as compared to oral conventional syrup and 9.66 times with reference to the OCG gel. The future perspective includes preclinical, toxicological and clinical studies for developing clinically viable formulation. PMID:22796784

Al Abood, Raid M; Talegaonkar, Sushama; Tariq, Mohammad; Ahmad, Farhan J

2013-01-01

236

MEMS based polymeric drug delivery system  

Microsoft Academic Search

In this paper, MEMS based polymeric drug delivery system for the treatment of cardiovascular disorder such as hypertension is presented. The major components of proposed system are drug delivery device, blood pressure sensor, flow sensor, electronic module, and power supply. Drug delivery device consists of piezoelectric actuator and reservoir integrated with side open polymeric microneedles. The in-depth theoretical and numerical

M. W. Ashraf; S. Tayyaba; N. Afzulpurkar

2010-01-01

237

Immune activation and target organ damage are consequences of hydrodynamic treatment but not delivery of naked siRNAs in mice.  

PubMed

Short-interfering RNAs (siRNAs), key mediators of RNA interference comprise a promising therapeutic tool, although side effects such as interferon (IFN) response are still not perfectly understood. Further, delivery to target organs is a major challenge, possibly associated with side effects including immune activation or organ damage. We investigated whether immune activation as a consequence of double-stranded RNA induced IFN response (Jak/STAT pathway activation or cytokine production) or target organ damage is induced by in vivo low-volume (LV) or high-volume (HV) hydrodynamic delivery or treatment with naked siRNA. NMRI mice were injected with naked siRNAs or saline by hydrodynamic injection (HDI) and positive control mice received polyinosinic-polycytidilic acid (poly I:C). LV (1?mL/mouse) and HV (10% of body weight) HDI were compared. After LV HDI, STAT1 and OAS1 gene expression inflammatory cytokine plasma levels and target organ injury were assessed. LV HDI induced slight alanine aminotransferase elevation and mild hepatocyte injury, whereas HV HDI resulted in high ALAT level and extensive hepatocyte necrosis. STAT1 or OAS1 was not induced by LV siRNA; however, HV saline led to a time-dependent slight increase in gene expression. Inflammatory cytokine plasma level and organ histology and functional parameters demonstrated no damage following LV HDI with or without siRNA. Our data demonstrate that naked siRNAs may be harnessed, without the induction of IFN response or immune activation, and that LV HDI is preferable, because HV HDI may cause organ damage. PMID:21749298

Rácz, Zsuzsanna; Godó, Mária; Révész, Csaba; Hamar, Péter

2011-06-01

238

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.

Mazzolani, Fabio; Togni, Stefano

2013-01-01

239

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

PubMed

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. PMID:24778349

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

2014-05-21

240

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

241

Accurate measurement of time  

NASA Astrophysics Data System (ADS)

The paper discusses current methods for accurate measurements of time by conventional atomic clocks, with particular attention given to the principles of operation of atomic-beam frequency standards, atomic hydrogen masers, and atomic fountain and to the potential use of strings of trapped mercury ions as a time device more stable than conventional atomic clocks. The areas of application of the ultraprecise and ultrastable time-measuring devices that tax the capacity of modern atomic clocks include radio astronomy and tests of relativity. The paper also discusses practical applications of ultraprecise clocks, such as navigation of space vehicles and pinpointing the exact position of ships and other objects on earth using the GPS.

Itano, Wayne M.; Ramsey, Norman F.

1993-07-01

242

An innovative matrix controlling drug delivery produced by thermal treatment of DC tablets containing polycarbophil and ethylcellulose.  

PubMed

An innovative matrix, produced by thermal treatment on direct compression (DC) tablets containing polycarbophil (POL) and ethylcellulose (EC), identified as matrix forming polymers, and able to control the release of diltiazem hydrochloride, was developed. At pH 7.2, 72 ± 1.2% (w/w) of drug loaded was released in 25 h, mostly at constant rate. This swellable and unerodible matrix controls drug release by an anomalous transport mechanism. The modifications induced by the thermal treatment are irreversible and can be used to control and characterize the matrix. A 3-component constrained mixture design allowed the investigation of the experimental domain in which the matrix forms and the computation of a mathematical model that can be used to optimize the formulation properties. The release rate can be modulated (0.032-0.064% drug released/min) through the choice of suitable treatment conditions and tablet composition. The maximum amount of diltiazem hydrochloride released by zero-order kinetics, at the lowest release rate, occurs for POL:EC ratio in the range of 1:1-2:3 with 20-30% of diluent. The tablets are able to load up to 50% (w/w) of diltiazem hydrochloride without losing their properties. A stability study performed on a selected formulation containing DTZ showed stability for at least 2.7 years at RT conditions. PMID:24144954

Caviglioli, Gabriele; Baldassari, Sara; Cirrincione, Paola; Russo, Eleonora; Parodi, Brunella; Gatti, Paolo; Drava, Giuliana

2013-12-15

243

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

244

Signaling, Delivery and Age as Emerging Issues in the Benefit/Risk Ratio Outcome of tPA For Treatment of CNS Ischemic Disorders  

PubMed Central

Stroke is a leading cause of morbidity and mortality. While tissue-type plasminogen activator (tPA) remains the only FDA approved treatment for ischemic stroke, clinical use of tPA has been constrained to roughly 3% of eligible patients because of the danger of intracranial hemorrhage and a narrow 3h time window for safe administration. Basic science studies indicate that tPA enhances excitotoxic neuronal cell death. In this review, the beneficial and deleterious effects of tPA in ischemic brain are discussed along with emphasis on development of new approaches towards treatment of patients with acute ischemic stroke. In particular, roles of tPA induced signaling and a novel delivery system for tPA administration based on tPA coupling to carrier red blood cells will be considered as therapeutic modalities for increasing tPA benefit/risk ratio. The concept of the neurovascular unit will be discussed in the context of dynamic relationships between tPA-induced changes in cerebral hemodynamics and histopathologic outcome of CNS ischemia. Additionally, the role of age will be considered since thrombolytic therapy is being increasingly used in the pediatric population, but there are few basic science studies of CNS injury in pediatric animals.

Armstead, William M; Ganguly, Kumkum; Kiessling, JW; Riley, John; Chen, Xiao-Han; Smith, Douglas H; Stein, Sherman C.; Higazi, Abd AR; Cines, Douglas B; Bdeir, Khalil; Zaitsev, Sergei; Muzykantov, Vladimir R.

2010-01-01

245

Intra-tumoral Gene Delivery of feIL-2, feIFN-? and feGM-CSF using Magnetofection as a Neoadjuvant Treatment Option for Feline Fibrosarcomas: A Phase-I Study  

Microsoft Academic Search

Summary Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra- tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats

A. Jahnke; J. Hirschberger; C. Fischer; T. Brill; R. Köstlin; C. Plank; H. Küchenhoff; S. Krieger; K. Kamenica; U. Schillinger

2007-01-01

246

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

247

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

248

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

249

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.

2014-01-01

250

Novel Delivery Strategies for Glioblastoma  

PubMed Central

Brain tumors—particularly glioblastoma multiforme (GBM)—pose an important public health problem in the US. Despite surgical and medical advances, the prognosis for patients with malignant gliomas remains grim: current therapy for is insufficient with nearly universal recurrence. A major reason for this failure is the difficulty of delivering therapeutic agents to the brain: better delivery approaches are needed to improve treatment. In this article, we summarize recent progress in drug delivery to the brain, with an emphasis on convection-enhanced delivery of nanocarriers. We examine the potential of new delivery methods to permit novel drug- and gene-based therapies that target brain cancer stem cells (BCSCs) and discuss the use of nanomaterials for imaging of tumors and drug delivery.

Zhou, Jiangbing; Atsina, Kofi-Buaku; Himes, Benjamin T.; Strohbehn, Garth W.; Saltzman, W. Mark

2012-01-01

251

Capillary Flowmeters for Accurate, Stable Flows of Gases.  

National Technical Information Service (NTIS)

Capillary flowmeters have been used for a number of years now to meter gases into flow systems. This report describes a flowmeter/controller that is accurate to 1% and delivers a constant flow independent of delivery pressure between 0-0.10 MPa (0-15 psia...

M. A. Dewilde

1980-01-01

252

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

253

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.

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

2014-01-01

254

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.

Uskokovic, Vuk; Desai, Tejal A.

2012-01-01

255

In vivo delivery of human acid ceramidase via cord blood transplantation and direct injection of lentivirus as novel treatment approaches for Farber disease  

PubMed Central

Farber disease is a rare lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (AC) activity and subsequent accumulation of ceramide. Currently, there is no treatment for Farber disease beyond palliative care and most patients succumb to the disorder at a very young age. Previously, our group showed that gene therapy using oncoretroviral vectors (RV) could restore enzyme activity in Farber patient cells. The studies described here employ novel RV and lentiviral (LV) vectors that engineer co-expression of AC and a cell surface marking transgene product, human CD25 (huCD25). Transduction of Farber patient fibroblasts and B cells with these vectors resulted in overexpression of AC and led to a 90% and 50% reduction in the accumulation of ceramide, respectively. Vectors were also evaluated in human hematopoietic stem/progenitor cells (HSPCs) and by direct in vivo delivery in mouse models. In a xenotransplantation model using NOD/SCID mice, we found that transduced CD34+ cells could repopulate irradiated recipient animals, as measured by CD25 expression. When virus was injected intravenously into mice, soluble CD25 was detected in the plasma and increased AC activity was present in the liver up to 14 weeks post-injection. These findings suggest that vector and transgene expression can persist long-term and offer the potential of a lasting cure. To our knowledge, this is the first report of in vivo testing of direct gene therapy strategies for Farber disease.

Ramsubir, Shobha; Nonaka, Takahiro; Girbes, Carmen Bedia; Carpentier, Stephane; Levade, Thierry; Medin, Jeffrey A.

2008-01-01

256

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

257

Drug delivery to the ear.  

PubMed

Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drug delivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions. PMID:23323784

Hoskison, E; Daniel, M; Al-Zahid, S; Shakesheff, K M; Bayston, R; Birchall, J P

2013-01-01

258

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.

Evans, C. H.

2012-01-01

259

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

260

The Impact of Retail-Sector Delivery of Artemether-Lumefantrine on Malaria Treatment of Children under Five in Kenya: A Cluster Randomized Controlled Trial  

PubMed Central

Background It has been proposed that artemisinin-based combination therapy (ACT) be subsidised in the private sector in order to improve affordability and access. This study in western Kenya aimed to evaluate the impact of providing subsidized artemether–lumefantrine (AL) through retail providers on the coverage of prompt, effective antimalarial treatment for febrile children aged 3–59 months. Methods and Findings We used a cluster-randomized, controlled design with nine control and nine intervention sublocations, equally distributed across three districts in western Kenya. Cross-sectional household surveys were conducted before and after the delivery of the intervention. The intervention comprised provision of subsidized packs of paediatric ACT to retail outlets, training of retail outlet staff, and community awareness activities. The primary outcome was defined as the proportion of children aged 3–59 months reporting fever in the past 2 weeks who started treatment with AL on the same day or following day of fever onset. Data were collected using structured questionnaires and analyzed based on cluster-level summaries, comparing control to intervention arms, while adjusting for other covariates. Data were collected on 2,749 children in the target age group at baseline and 2,662 at follow-up. 29% of children experienced fever within 2 weeks before the interview. At follow-up, the percentage of children receiving AL on the day of fever or the following day had risen by 14.6% points in the control arm (from 5.3% [standard deviation (SD): 3.2%] to 19.9% [SD: 10.0%]) and 40.2% points in the intervention arm (from 4.7% [SD: 3.4%] to 44.9% [SD: 11.7%]). The percentage of children receiving AL was significantly greater in the intervention arm at follow-up, with a difference between the arms of 25.0% points (95% confidence interval [CI]: 14.1%, 35.9%; unadjusted p?=?0.0002, adjusted p?=?0.0001). No significant differences were observed between arms in the proportion of caregivers who sought treatment for their child's fever by source, or in the child's adherence to AL. Conclusions Subsidizing ACT in the retail sector can significantly increase ACT coverage for reported fevers in rural areas. Further research is needed on the impact and cost-effectiveness of such subsidy programmes at a national scale. Trial Registration Current Controlled Trials ISRCTN59275137 and Kenya Pharmacy and Poisons Board Ethical Committee for Clinical Trials PPB/ECCT/08/07. Please see later in the article for the Editors' Summary

Kangwana, Beth P.; Kedenge, Sarah V.; Noor, Abdisalan M.; Alegana, Victor A.; Nyandigisi, Andrew J.; Pandit, Jayesh; Fegan, Greg W.; Todd, James E.; Brooker, Simon; Snow, Robert W.; Goodman, Catherine A.

2011-01-01

261

Efficacy of a New Pattern of Delivery of Methylphenidate for the Treatment of ADHD: Effects on Activity Level in the Classroom and on the Playground  

Microsoft Academic Search

Objective:To evaluate the pharmacodynamic effects of an experimental (EXP) delivery of methylphenidate (MPH) in children with attention-deficit\\/hyperactivity disorder and to investigate the situational nature of effects in laboratory classroom and playground settings.

JAMES M. SWANSON; SUNEEL GUPTA; LILLIE WILLIAMS; DAVE AGLER; MARC LERNER; SHARON WIGAL

2002-01-01

262

Cell-Mediated Drugs Delivery  

PubMed Central

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

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

2011-01-01

263

Accelerated Partial Breast Irradiation: Using the CyberKnife as the Radiation Delivery Platform in the Treatment of Early Breast Cancer  

PubMed Central

We evaluate the CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) for non-invasive delivery of accelerated partial breast irradiation (APBI) in early breast cancer patients. Between 6/2009 and 5/2011, nine patients were treated with CyberKnife APBI. Normal tissue constraints were imposed as outlined in the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 (NSABP/RTOG) Protocol (Vicini and White, 2007). Patients received a total dose of 30?Gy in five fractions (group 1, n?=?2) or 34?Gy in 10 fractions (group 2, n?=?7) delivered to the planning treatment volume (PTV) defined as the clinical target volume (CTV) +2?mm. The CTV was defined as either the lumpectomy cavity plus 10?mm (n?=?2) or 15?mm (n?=?7). The cavity was defined by a T2-weighted non-contrast breast MRI fused to a planning non-contrast thoracic CT. The CyberKnife Synchrony system tracked gold fiducials sutured into the cavity wall during lumpectomy. Treatments started 4–5?weeks after lumpectomy. The mean PTV was 100?cm3 (range, 92–108?cm3) and 105?cm3 (range, 49–241?cm3) and the mean PTV isodose prescription line was 70% for groups 1 and 2, respectively. The mean percent of whole breast reference volume receiving 100 and 50% of the dose (V100 and V50) for group 1 was 11% (range, 8–13%) and 23% (range, 16–30%) and for group 2 was 11% (range, 7–14%) and 26% (range, 21–35.0%), respectively. At a median 7?months follow-up (range, 4–26?months), no acute toxicities were seen. Acute cosmetic outcomes were excellent or good in all patients; for those patients with more than 12?months follow-up the late cosmesis outcomes were excellent or good. In conclusion, the lack of observable acute side effects and current excellent/good cosmetic outcomes is promising. We believe this suggests the CyberKnife is a suitable non-invasive radiation platform for delivering APBI with achievable normal tissue constraints.

Vermeulen, Sandra; Cotrutz, Cristian; Morris, Astrid; Meier, Robert; Buchanan, Claire; Dawson, Patricia; Porter, Bruce

2011-01-01

264

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.

Ferrara, Katherine W.

2009-01-01

265

Accurate \\  

Microsoft Academic Search

We analyse a system in which, due to entanglement between the spin and\\u000aspatial degrees of freedom, the reduced transmitted state has the shape of the\\u000afreely propagating pulse translated in the complex co-ordinate plane. In the\\u000acase an apparently \\

D. Sokolovski; R. Sala Mayato

2009-01-01

266

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

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/cm(2) and significantly dropped, by about 50%, at higher particle concentrations (4 and 8 mg/cm(2)). The gene expression of osteocalcin, a mineralization inductor, and the transcription factor Runx2 was downregulated in cells incubated in the presence of 3 mg/cm(2) 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

2014-02-01

267

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.

USKOKOVIC, VUK; DESAI, TEJAL A.

2014-01-01

268

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

269

Isolation of drug delivery from drug effect: Problems of optimizing drug delivery parameters1  

Microsoft Academic Search

A recurring question in the treatment of malignant brain tumors has been whether treatment failure is due to inadequate delivery or ineffective drugs. To isolate these issues, we tested a paradigm in which the \\

Mir J. Ali; Yot Navalitloha; Michael W. Vavra; Y. Kang; Andrea C. Itskovich; Peter Molnar; Robert M. Levy; Dennis R. Groothuis

2006-01-01

270

Accurately diagnosing commonly misdiagnosed circular rashes.  

PubMed

Rashes are common in the pediatric population yet can be quite problematic for nurse practitioners to diagnose. A thorough history and physical examination, along with some simple procedures, will aid in identifying these skin conditions. Four cases are presented, which may initially prove challenging to diagnose, and symptoms are categorically examined to arrive at the accurate diagnoses. Treatment guidelines, options, and the role of parental education and involvement also are discussed. PMID:17907732

Popovich, Debbie; McAlhany, Allison

2007-01-01

271

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.

2003-01-01

272

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

273

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.  

PubMed

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 × 27 matrix with an active area of 27 × 27 cm² 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. PMID:21741819

Syamkumar, S A; Padmanabhan, Sriram; Sukumar, Prabakar; Nagarajan, Vivekanandan

2012-01-01

274

Treatment planning and delivery of involved field radiotherapy in advanced Hodgkin's disease: results from a questionnaire-based audit for the UK Stanford V regimen vs ABVD clinical trial quality assurance programme (ISRCTN 64141244).  

PubMed

This questionnaire forms the basis of the quality assurance (QA) programme for the UK randomized Phase III study of the Stanford V regimen versus ABVD for treatment of advanced Hodgkin's disease to assess differences between participating centres in treatment planning and delivery of involved-field radiotherapy for Hodgkin's lymphoma The questionnaire, which was circulated amongst 42 participating centres, consisted of seven sections: target volume definition and dose prescription; critical structures; patient positioning and irradiation techniques; planning; dose calculation; verification; and future developments The results are based on 25 responses. One-third plan using CT alone, one-third use solely the simulator and the rest individualize, depending on disease site. Eleven centres determine a dose distribution for each patient. Technique depends on disease site and whether CT or simulator planning is employed. Most departments apply isocentric techniques and use immobilization and customized shielding. In vivo dosimetry is performed in 7 centres and treatment verification occurs in 24 hospitals. In conclusion, the planning and delivery of treatment for lymphoma patients varies across the country. Conventional planning is still widespread but most centres are moving to CT-based planning and virtual simulation with extended use of immobilization, customized shielding and compensation. PMID:17959922

Diez, P; Hoskin, P J; Aird, E G A

2007-10-01

275

Local drug delivery to the brain  

Microsoft Academic Search

The controlled local delivery of antineoplastic agents by biodegradable polymers is a technique that allows for exposure of tumor cells to therapeutic doses of an active agent for prolonged periods of time while avoiding high systemic doses associated with debilitating toxicities. The use of polymers for chemotherapy delivery expands the spectrum of available treatment of neoplasms in the central nervous

Paul P Wang; James Frazier; Henry Brem

2002-01-01

276

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

277

Identifying Less Accurately Measured Students  

Microsoft Academic Search

Abstract Some students are less accurately measured,by typical reading tests than other students. By asking teachers to identify students whose performance,on state reading tests would likely underestimate their reading skills, this study sought to learn about characteristics of less accurately measured,students while also evaluating how well teachers can make such judgments. Twenty students identified by eight teachers participated in structured

Ross Moen; Kristi Liu; Martha Thurlow; Adam Lekwa; Sarah Scullin; Kristin Hausmann

278

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

279

Drug delivery systems: An updated review  

PubMed Central

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time.

Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K

2012-01-01

280

Novel central nervous system drug delivery systems.  

PubMed

For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases. PMID:24325540

Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

2014-05-01

281

The potential for the noninvasive delivery of polymeric nanocarriers using propellant-based inhalers in the treatment of Chlamydial respiratory infections  

Microsoft Academic Search

A novel strategy for pulmonary delivery of polymeric nanocarriers (NCs) pressurized-metered dose inhalers (pMDIs) is reported in this work. Core–shell particles consisting of a water soluble, hydrofluoroalkane(HFA)-philic biodegradable copolymer of chitosan and poly(lactic acid), and a core of poly(d,l-lactide-co-glycolide) (PLGA) NCs were prepared by a modified emulsification–diffusion methodology. Dispersions of the core–shell particles in HFA propellant revealed enhanced physical stability

Balaji Bharatwaj; Libo Wu; Judith A. Whittum-Hudson; Sandro R. P. da Rocha

2010-01-01

282

Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery  

Microsoft Academic Search

Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the ?v?3 and ?v?5 integrins. Preclinical studies demonstrate\\u000a antiangiogenic activity and anti-invasive activity in a number of glioma models. This study was designed to evaluate the efficacy\\u000a and tumor delivery of cilengitide in patients with recurrent glioblastoma. Patients with recurrent glioblastoma who require\\u000a a surgical resection for optimal clinical

Mark R. Gilbert; John Kuhn; Kathleen R. Lamborn; Frank Lieberman; Patrick Y. Wen; Minesh Mehta; Timothy Cloughesy; Andrew B. Lassman; Lisa M. DeAngelis; Susan Chang; Michael Prados

283

Letrozole dispersed on poly (vinyl alcohol) anchored maleic anhydride grafted low density polyethylene: a controlled drug delivery system for treatment of breast cancer.  

PubMed

The present work focuses on the design of a drug delivery system for systemic, controlled release of the poorly soluble breast cancer drug, letrozole. The drug delivery system was prepared in two steps: a low density polyethylene (LDPE) substrate surface was grafted with maleic anhydride (MA) via solution grafting technique. Next, the grafted substrate was used to anchor a hydrophilic polymeric drug release system consisting of poly (vinyl alcohol) (PVA). The PVA anchored MA grafted LDPE (PVA/MA-g-LDPE) drug release system was used for the controlled release of letrozole. This system was characterized using ATR-FTIR spectrophotometry, surface profilometry, and scanning electron microscopy. Biocompatibility studies were also carried out. In vitro release studies of letrozole from the system were performed in distilled water and phosphate buffer saline (PBS) at 37°C. Release of ?90% letrozole from hydrophilic PVA matrix was observed within a period of 35 days. A high correlation coefficient (R(2)=0.99) was seen between the release of letrozole in distilled water and PBS. Cytotoxicity studies using MTT colorimetric assay suggested that all samples were biocompatible. It is concluded that the letrozole delivery system appears to overcome the limitations associated with letrozole by providing enhanced drug dissolution rate, controlled release and improved bioavailability of the incorporated drug and, therefore, seems to have extended therapeutic effects. PMID:24463149

Siddiqa, Akhtar Jahan; Chaudhury, Koel; Adhikari, Basudam

2014-04-01

284

Optimal delivery of DMLC Arc Therapy  

Microsoft Academic Search

Purpose: The continuous delivery of a specific treatment plan for an arc therapy can be achieved with multiple solutions for speed\\u000a of gantry rotation, beam dose rate variation in time and with various speed trajectories of MLC leaves. This non-uniqueness\\u000a of arc therapy delivery creates situations that given treatment plans can be delivered with arc with variable degrees of efficiency.

Lech Papiez; Dharanipathy Rangaraj

285

Nanobiotechnology-Based Drug Delivery to the Central Nervous System  

Microsoft Academic Search

Background: Drug delivery across the blood-brain barrier (BBB) is a major limitation in the treatment of central nervous system (CNS) disorders. Several approaches are being investigated to improve drug delivery across the BBB. Objective\\/Methods: This review deals with the role of nanobiotechnology in CNS drug delivery. The small size of the nanoparticles enables them to penetrate the BBB and facilitate

K. K. Jain

2007-01-01

286

Accurate Replication in Genetic Programming  

Microsoft Academic Search

Abstract One characteristic tendency of genetic program - ming is the production of considerably larger trees than expected It has been suggested that this is related to the ability of individuals to replicate ac - curately In this paper we present theoretical anal - ysis which shows that, for certain specific cases, the pressure for accurate replication induces an increase

Nicholas Freitag Mcphee; Justin Darwin Miller

1995-01-01

287

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.

Prausnitz, Mark R.; Langer, Robert

2009-01-01

288

Accurate dosimetry for monitoring response to photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is becoming a treatment of choice for cancer because of its low cost, high effectiveness and low damage to healthy tissue. Successful PDT outcome depends on accurate dosimetry, which is currently lacking, leading to variable and/or ineffective treatment outcome. We report on our research and developmental efforts towards an implicit dosimetric method for PDT that will provide an accurate assessment of treatment effectiveness by continuous monitoring of the in vivo drug concentration and the oxygen concentration in tissue. This approach uses the same tools presently available for PDT, making it attractive to the health professionals without increasing treatment cost.

Seetamraju, M.; Gurjar, R. S.; Myers, R.; Hasan, T.; Wolf, D. E.

2012-02-01

289

Targeted Spinal Cord Therapeutics Delivery: Stabilized Platform and Microelectrode Recording Guidance Validation  

Microsoft Academic Search

Background\\/Aims: No validated delivery technique exists for accurate, reproducible delivery of biological therapies to discrete spinal cord targets. To address this unmet need, we have constructed a stabilized platform capable of supporting physiologic mapping, through microelectrode recording, and cellular or viral payload delivery to the ventral horn. Methods: A porcine animal model (n = 7) has been chosen based upon

Jonathan Riley; John Butler; Kenneth B. Baker; Shearwood McClelland III; Qingshan Teng; Jun Yang; Mary Garrity-Moses; Thais Federici; Nicholas M. Boulis

2008-01-01

290

Time resolved mass flow measurements for a fast gas delivery system  

Microsoft Academic Search

A technique is demonstrated whereby the delivered mass and flow rate versus time of a short rise-time gas delivery system may be accurately determined. The gas mass M that flows past a point in a gas delivery system by an arbitrary time t=tp may be accurately measured if that point is sealed off with a fast closing valve within a

E. L. Ruden; J. H. Degnan; T. W. Hussey; M. C. Scott; J. D. Graham; S. K. Coffey

1993-01-01

291

Helical Tomotherapy-Based STAT Stereotactic Body Radiation Therapy: Dosimetric Evaluation for a Real-Time SBRT Treatment Planning and Delivery Program  

Microsoft Academic Search

Stereotactic body radiation therapy (SBRT) treatments have high-dose gradients and even slight patient misalignment from the simulation to treatment could lead to target underdosing or organ at risk (OAR) overdosing. Daily real-time SBRT treatment planning could minimize the risk of geographic miss. As an initial step toward determining the clinical feasibility of developing real-time SBRT treatment planning, we determined the

Neal Dunlap; Alyson McIntosh; Ke Sheng; Wensha Yang; Benton Turner; Asal Shoushtari; Jason Sheehan; David R. Jones; Weigo Lu; Keneth Ruchala; Gustavo Olivera; Donald Parnell; James L. Larner; Stanley H. Benedict; Paul W. Read

2010-01-01

292

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

293

Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors.  

PubMed

Adequate retention in systemic circulation is the preliminary requirement for systemic gene delivery to afford high bioavailability into the targeted site. Polyplex micelle formulated through self-assembly of oppositely-charged poly(ethylene glycol) (PEG)-polycation block copolymer and plasmid DNA has gained tempting perspective upon its advantageous core-shell architecture, where outer hydrophilic PEG shell offers superior stealth behaviors. Aiming to promote these potential characters toward systemic applications, we strategically introduced hydrophobic cholesteryl moiety at the ?-terminus of block copolymer, anticipating to promote not only the stability of polyplex structure but also the tethered PEG crowdedness. Moreover, Mw of PEG in the PEGylated polyplex micelle was elongated up to 20 kDa for expecting further enhancement in PEG crowdedness. Furthermore, cyclic RGD peptide as ligand molecule to integrin receptors was installed at the distal end of PEG in order for facilitating targeted delivery to the tumor site as well as promoting cellular uptake and intracellular trafficking behaviors. Thus constructed cRGD conjugated polyplex micelle with the elevated PEG shielding was challenged to a modeled intractable pancreatic cancer in mice, achieving potent tumor growth suppression by efficient gene expression of antiangiogenic protein (sFlt-1) at the tumor site. PMID:24439417

Ge, Zhishen; Chen, Qixian; Osada, Kensuke; Liu, Xueying; Tockary, Theofilus A; Uchida, Satoshi; Dirisala, Anjaneyulu; Ishii, Takehiko; Nomoto, Takahiro; Toh, Kazuko; Matsumoto, Yu; Oba, Makoto; Kano, Mitsunobu R; Itaka, Keiji; Kataoka, Kazunori

2014-03-01

294

From accurate machining towards accurate measurements with MICROSCOPE  

NASA Astrophysics Data System (ADS)

Observing any violation of the Equivalence Principle at a level as low as 10 -15 needs both a very soft and stable environment and a very accurate instrument The MICROSCOPE space laboratory allows testing of the universality of free fall with two masses made of a Platinum Rhodium alloy and a Titanium alloy in a 10 pico-g environment The two test-masses are accurately controlled by electrostatic forces to follow a common geodesic within a CNES drag-free microsatellite Accurate centring and alignment of the test-masses is mandatory to prevent any artefact signal due to the Earth s gravity gradient or any on-board gravity gradient To this purpose the MICROSCOPE instrument called Twin-Space Accelerometer for Gravitation Experimentation T-SAGE has been designed to minimise the gravity gradient disturbances A laboratory model and a first representative model for vibration tests have been produced integrated and tested These models have allowed verification of the manufacturing and integration processes and of their accuracy which gives a first budget for the expected centring and alignment of the flight-models This paper describes the micro-meter machining and integration challenges of T-SAGE and their impact on the instrument performance In particular the shape of the test-mass has an effect on the differential accelerometer output due to the gravity gradient and also on the instrument capacitive position output used for the electrostatic servo-loop First results obtained with the fully integrated models are also presented to assess the

Rodrigues, M.; Touboul, P.; Chhun, R.; Hudson, D.; Foulon, B.; Flinoise, P.; Bodoville, G.; Lebat, V.

295

Delivery Performance Indicators.  

National Technical Information Service (NTIS)

Delivery of equipment in accordance with the user's required schedule is essential to DARCOM's materiel readiness mission. However, DARCOM is experiencing increasing problems with delinquent deliveries. For DARCOM's major subordinate activities, delinquen...

H. F. Candy R. C. Brannon S. H. Carter

1977-01-01

296

An Extension of the `MLR' Potential Function Form which Allows for AN Accurate Dpf Treatment of Li_2(1^3?^+_g), which Couples to Two Other States Near Their Asymptotes  

NASA Astrophysics Data System (ADS)

The only potential energy functions for the 1^3?^+_g state of Li_2 published to date were conventional RKR curves based on experimental data for the vibrational levels v=1-7, and they do not yield realistic predictions for the very weakly bound levels v=62 - 89 for ^{7,7}Li_2 and v=59 - 79 for ^{6,6}Li_2, which were subsequently observed using photoassociation spectroscopy (PAS). A recent analysis of data for the 1 ^3?_g^+ -a ^3?_u^+ and 2 ^3?_g -a ^3?_u^+ systems of Li_2 was unable to incorporate these PAS data, and this was due to the lack of a potential function form with the ability to accurately describe the behaviour of the potential for a molecule which becomes coupled to two other distinct states near the dissociation asymptote. The current work presents and tests an extension of the `Morse/Long-Range' (MLR) potential function form which does provide an accurate description of the 1^3?^+_g- state potential at all internuclear distances, including the long-range region where the three-state coupling occurs. The extension is based on expressions reported by Aubert-Frécon and co-workers, which show that the long-range tail of this potential is one of the eigenvalues of a 3x3 Hamiltonian matrix. Accordingly, this extension requires the diagonalization of this matrix at each internuclear distance r. Although this can be done analytically, we show that the diagonalization is in fact computed more efficiently numerically, and leads to a more accurate potential energy function. F. Martin et al., Spectrochimica Acta 44A, 1369 (1988) C. Linton et al., J. Chem. Phys. 91, 6036 (1989). W.I. McAlexander et al., Phys. Rev. A 51, R871 (1995) E.R.I. Abraham et al. J. Chem. Phys. 103, 7773 (1995) N.S. Dattani, et al., 63rd Ohio State University Int. Symp. on Molec. Spec. (2008), paper RC11. R.J. Le Roy and R.D.E. Henderson, Mol. Phys. 105, 663 (2007) R.J. Le Roy et al., J. Chem. Phys. (2009, submitted). Martin et al., Phys, Rev. A 55, 3458 (1997) M. Aubert-Frecon et al., J. Mol. Spectrosc. 192, 239 (1998).

Dattani, Nikesh S.; Le Roy, Robert J.; Ross, Amanda J.; Linton, Colan

2009-06-01

297

Binding of liposomes to human bladder tumor epithelial cell lines: implications for an intravesical drug delivery system for the treatment of bladder cancer.  

PubMed

Present therapy of human superficial bladder cancer includes the intravesical administration of antitumor drugs and immunomodulators. The purpose of these studies was to determine whether liposomes can bind to human bladder cancer cells and thereby provide a mechanism to improve the delivery of anticancer agents to diseased urothelium. Negatively charged large multilamellar vesicles (MLVs) bound to four different human bladder tumor cell lines (253J, J82, T24, TCCSUP) more avidly than did small sonicated vesicles or vesicles consisting of uncharged phosphatidylcholine (PC). Of the three types of negatively charged MLVs tested, phosphatidylcholine/phosphatidylserine (7:3, mol ratio) (PC/PS) MLVs bound the most. MLV binding to tumor cells was saturable and appeared to be specific. In contrast, the binding of liposomes to normal fetal bladder cells was minimal. These data suggest that targeting of drugs to superficial bladder cancer can be achieved by the intravesical administration of PC/PS MLV. PMID:2623380

Johnson, J W; Nayar, R; Killion, J J; von Eschenbach, A C; Fidler, I J

1989-01-01

298

[Bacterial vaginosis and preterm delivery].  

PubMed

Bacterial vaginosis (BV) is an imbalance of vaginal flora. There is a statistical association between BV in early pregnancy and the occurrence of obstetric complications including preterm delivery. If screening and treatment of asymptomatic BV in patients at low risk are not recommended, the management of patients at high risk of prematurity is controversial. Using molecular tool, a rational and objective approach to the imbalance of vaginal flora, would reassess the relationship between VB and obstetric complications. PMID:22192689

Menard, J-P; Bretelle, F

2012-01-01

299

Conventional topical delivery systems.  

PubMed

Effective dermatologic therapy depends on both the active drug and the properties of the delivery system. A topical delivery system, or vehicle, is defined as the substance that carries a specific drug into contact with and through the skin. The challenge to topical drug delivery is the transport across the skin barrier. Depending on the delivery system, penetration of the active drug can be quite variable and this is largely due to the physiochemical properties of the constituent components of that vehicle. Selection of the appropriate drug delivery system will depend on the active, anatomic site of disease and patient preferences. PMID:22353153

Weiss, Stefan C

2011-01-01

300

NCI Image Guided Drug Delivery Summit  

PubMed Central

On April 17th 2010 scientists from academia, the National Cancer Institute (NCI), and the Food and Drug Administration (FDA) assembled at “The NCI Image Guided Drug Delivery Summit,” in Washington DC, to discuss recent advances, barriers, opportunities and regulatory issues related to the field. The meeting included a scientific session and an NCI/FDA session, followed by a panel discussion of speakers from both sessions. Image guided drug delivery (IGDD) in cancer is a form of individualized therapy where imaging methods are used in guidance and monitoring of localized and targeted delivery of therapeutics to the tumor. So a systematic approach to IGDD requires mechanisms for targeting, delivery, activation and monitoring of the process. While the goal in IGDD is to optimize the therapeutic ratio through personalized image-guided treatments, a major challenge is in overcoming the biological barriers to the delivery of therapeutics into tumors and cells. Speakers discussed potential challenges to clinical translation of nano-based drug delivery systems including in-vivo characterization of nanocarriers, pre-clinical validation of targeting and delivery, studies of biodistribution, pharmacokinetics, pharmacodynamics and toxicity as well as scale-up manufacturing of delivery systems. Physiological and quantitative imaging techniques may serve as enabling tools that could potentially transform many existing challenges into opportunities for advancement of the field.

Tandon, Pushpa

2010-01-01

301

Verification of helical tomotherapy delivery using autoassociative kernel regression.  

PubMed

Quality assurance (QA) is a topic of major concern in the field of intensity modulated radiation therapy (IMRT). The standard of practice for IMRT is to perform QA testing for individual patients to verify that the dose distribution will be delivered to the patient. The purpose of this study was to develop a new technique that could eventually be used to automatically evaluate helical tomotherapy treatments during delivery using exit detector data. This technique uses an autoassociative kernel regression (AAKR) model to detect errors in tomotherapy delivery. AAKR is a novel nonparametric model that is known to predict a group of correct sensor values when supplied a group of sensor values that is usually corrupted or contains faults such as machine failure. This modeling scheme is especially suited for the problem of monitoring the fluence values found in the exit detector data because it is able to learn the complex detector data relationships. This scheme still applies when detector data are summed over many frames with a low temporal resolution and a variable beam attenuation resulting from patient movement. Delivery sequences from three archived patients (prostate, lung, and head and neck) were used in this study. Each delivery sequence was modified by reducing the opening time for random individual multileaf collimator (MLC) leaves by random amounts. The errof and error-free treatments were delivered with different phantoms in the path of the beam. Multiple autoassociative kernel regression (AAKR) models were developed and tested by the investigators using combinations of the stored exit detector data sets from each delivery. The models proved robust and were able to predict the correct or error-free values for a projection, which had a single MLC leaf decrease its opening time by less than 10 msec. The model also was able to determine machine output errors. The average uncertainty value for the unfaulted projections ranged from 0.4% to 1.8% of the detector signal. The low model uncertainty indicates that the AAKR model is extremely accurate in its predictions and also suggests that the model may be able to detect errors that cause the fluence to change by less than 2%. However, additional evaluation of the AAKR technique is needed to determine the minimum detectable error threshold from the compressed helical tomotherapy detector data. Further research also needs to explore applying this technique to electronic portal imaging detector data. PMID:17879788

Seibert, Rebecca M; Ramsey, Chester R; Garvey, Dustin R; Hines, J Wesley; Robison, Ben H; Outten, Samuel S

2007-08-01

302

Extending Use of Direct Behavior Rating Beyond Student AssessmentApplications to Treatment Integrity Assessment Within a Multi-Tiered Model of School-Based Intervention Delivery  

Microsoft Academic Search

To make valid decisions about intervention effectiveness in a tiered intervention system, it is essential to formatively assess treatment integrity along with student outcomes. Despite significant advances in technologies for ongoing assessment of student outcomes, research regarding treatment integrity assessment has not shared the same progress in that most available methods lack adequate psychometric evidence and require significant resources. Direct

Lisa M. Hagermoser Sanetti; Sandra M. Chafouleas; Theodore J. Christ; Katie L. Gritter

2009-01-01

303

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

304

Formulations for trans-tympanic antibiotic delivery.  

PubMed

We have developed a drug delivery system for prolonged trans-tympanic antibiotic delivery from a single dose administration. Increased permeability to ciprofloxacin of the intact tympanic membrane (TM) was achieved by chemical permeation enhancers (CPEs--bupivacaine, limonene, sodium dodecyl sulfate); this was also seen by CPEs contained within a hydrogel (poloxamer 407) to maintain the formulation at the TM. The CPE-hydrogel formulation had minimal effects on auditory thresholds and tissue response in vivo. CPE-hydrogel formulations have potential for ototopical delivery of ciprofloxacin for the treatment of acute otitis media (AOM) and other middle ear diseases. PMID:23146430

Khoo, Xiaojuan; Simons, Emmanuel J; Chiang, Homer H; Hickey, Julia M; Sabharwal, Vishakha; Pelton, Stephen I; Rosowski, John J; Langer, Robert; Kohane, Daniel S

2013-01-01

305

COROT mission: accurate stellar photometry  

NASA Astrophysics Data System (ADS)

The COROT mission is dedicated to stellar seismology and search for telluric extra-solar planets. The development is led by CNES in association with French laboratories (LESIA, LAM and IAS) and several European partners (Germany, Belgium, Austria, Spain, ESA and Brasilia). The COROT seismology program will measure periodic variations with amplitude of 2.10 -6 of the photon flux emitted by bright stars. The COROT exoplanet program will detect the presence of exoplanets using the radiometric occultation method. The need is to detect photons flux variations about 7×10-4 for one hour integration time. Such performance will permit to detect occultations on a very large number of stars: magnitude between 12 and 15.5. The satellite Preliminary Design Review has been held on January 2004 while the instrument is already in development phase with a Critical Design Review in April 2004 and a delivery of the flight model in March 2005. The launch is scheduled in June 2006. This paper recalls the mission, describes the payload and its main noise performances.

Costes, Vincent; Bodin, Pierre; Levacher, Patrick; Auvergne, Michel

2004-06-01

306

Clinical Issues in Mental Health Service Delivery to Refugees.  

ERIC Educational Resources Information Center

Serious limitations exist in the delivery of mental health services to refugees throughout the resettlement process: fragmentation, instability, language barriers, culturally inappropriate treatment methods, and severe staff shortages. Suggested improvements for refugee mental health services emphasize outreach, prevention, treatment approaches,…

Gong-Guy, Elizabeth; And Others

1991-01-01

307

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.

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

308

Predict amine solution properties accurately  

SciTech Connect

Improved process design begins with using accurate physical property data. Especially in the preliminary design stage, physical property data such as density viscosity, thermal conductivity and specific heat can affect the overall performance of absorbers, heat exchangers, reboilers and pump. These properties can also influence temperature profiles in heat transfer equipment and thus control or affect the rate of amine breakdown. Aqueous-amine solution physical property data are available in graphical form. However, it is not convenient to use with computer-based calculations. Developed equations allow improved correlations of derived physical property estimates with published data. Expressions are given which can be used to estimate physical properties of methyldiethanolamine (MDEA), monoethanolamine (MEA) and diglycolamine (DGA) solutions.

Cheng, S.; Meisen, A. [Univ. of British Columbia, Vancouver, British Columbia (Canada); Chakma, A. [Univ. of Calgary, Alberta (Canada)

1996-02-01

309

Decreased treatment times with aerosolized iloprost following increase in power levels for the I-neb Adaptive Aerosol Delivery (AAD) System  

Microsoft Academic Search

Summary The I-neb AAD System (I-neb) is the 3 rd generation AAD System following HaloLite and Prodose. We compared in vitro iloprost output rates, treatment times, MMADs for the three generations of AAD Systems (I-neb, power levels 6, 10 and 15). A breathing simulator was used to measure output rates, treatment times; an impactor setup for determination of MMADs. Mean

Robert Van Dyke; Kurt Nikander

310

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

311

Advances in adult asthma diagnosis and treatment and health outcomes, education, delivery, and quality in 2011: what goes around comes around.  

PubMed

Last year's review of research advances in adults with asthma emphasized the linear trajectory of translation: the initial studies translating bench findings to the first patients (T1) are connected to larger efficacy studies, including clinical trials studying subjects under tightly controlled conditions (T2), and these in turn are connected to research, including comparative effectiveness research, that tests how the efficacy findings of T2 research fare in the real world, diverse populations, and varied practice settings (T3). This year what was observed was a more interwoven relationship (rather than a linear one), in which each translational level informs the others and new approaches to answering old questions have led to new discoveries. Within this framework, the present review summarizes clinical research on asthma in adults that was reported in the Journal of Allergy and Clinical Immunology in 2011, with emphasis on health outcomes, education, delivery, and quality in terms of discoveries related to mechanisms of disease, environmental exposures, and management. PMID:22130423

Apter, Andrea J

2012-01-01

312

Mathematical modeling of drug delivery.  

PubMed

Due to the significant advances in information technology mathematical modeling of drug delivery is a field of steadily increasing academic and industrial importance with an enormous future potential. The in silico optimization of novel drug delivery systems can be expected to significantly increase in accuracy and easiness of application. Analogous to other scientific disciplines, computer simulations are likely to become an integral part of future research and development in pharmaceutical technology. Mathematical programs can be expected to be routinely used to help optimizing the design of novel dosage forms. Good estimates for the required composition, geometry, dimensions and preparation procedure of various types of delivery systems will be available, taking into account the desired administration route, drug dose and release profile. Thus, the number of required experimental studies during product development can be significantly reduced, saving time and reducing costs. In addition, the quantitative analysis of the physical, chemical and potentially biological phenomena, which are involved in the control of drug release, offers another fundamental advantage: The underlying drug release mechanisms can be elucidated, which is not only of academic interest, but a pre-requisite for an efficient improvement of the safety of the pharmaco-treatments and for effective trouble-shooting during production. This article gives an overview on the current state of the art of mathematical modeling of drug delivery, including empirical/semi-empirical and mechanistic realistic models. Analytical as well as numerical solutions are described and various practical examples are given. One of the major challenges to be addressed in the future is the combination of mechanistic theories describing drug release out of the delivery systems with mathematical models quantifying the subsequent drug transport within the human body in a realistic way. Ideally, the effects of the design parameters of the dosage form on the resulting drug concentration time profiles at the site of action and the pharmacodynamic effects will become predictable. PMID:18822362

Siepmann, J; Siepmann, F

2008-12-01

313

Intravenous drug delivery in neonates: lessons learnt.  

PubMed

Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics. PMID:24482352

Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S

2014-06-01

314

Considerations in insulin delivery device selection.  

PubMed

Recent guidelines from the American Diabetes Association and the European Association for the Study of Diabetes promote the use of insulin sooner rather than later in patients with type 2 diabetes to achieve goal range glucose control (< 7%) but remain silent on a recommendation for delivery system. Even though there is widespread consensus among experts and payers that people with type 2 diabetes should use insulin earlier to achieve tight control, it still remains an elusive goal. Benefits of pen-type delivery devices include accurate dosing, faster and easier setting of dose and injection times, and increased patient acceptance and adherence. Before healthcare professionals can recommend a delivery device, it is critical they understand not only the medication in the device but also the various features and benefits to the different devices available and how those impact the patient. We will present considerations to assist in making appropriate device selection, to optimize patient success. PMID:20515315

Valentine, Virginia; Kruger, Davida F

2010-06-01

315

Distinct cell shapes determine accurate chemotaxis  

PubMed Central

The behaviour of an organism often reflects a strategy for coping with its environment. Such behaviour in higher organisms can often be reduced to a few stereotyped modes of movement due to physiological limitations, but finding such modes in amoeboid cells is more difficult as they lack these constraints. Here, we examine cell shape and movement in starved Dictyostelium amoebae during migration toward a chemoattractant in a microfluidic chamber. We show that the incredible variety in amoeboid shape across a population can be reduced to a few modes of variation. Interestingly, cells use distinct modes depending on the applied chemical gradient, with specific cell shapes associated with shallow, difficult-to-sense gradients. Modelling and drug treatment reveals that these behaviours are intrinsically linked with accurate sensing at the physical limit. Since similar behaviours are observed in a diverse range of cell types, we propose that cell shape and behaviour are conserved traits.

Tweedy, Luke; Meier, Born; Stephan, Jurgen; Heinrich, Doris; Endres, Robert G.

2013-01-01

316

Accurate models for EUV lithography  

NASA Astrophysics Data System (ADS)

Accurate modeling of EUV Lithography is a mandatory step in driving the technology towards its foreseen insertion point for 22-16nm node patterning. The models are needed to correct EUV designs for imaging effects, and to understand and improve the CD fingerprint of the exposure tools. With a full-field EUV ADT from ASML now available in the IMEC cleanroom, wafer data can be collected to calibrate accurate models and check if the existing modeling infrastructure can be extended to EUV lithography. As a first topic, we have measured the CD on wafer of a typical OPC dataset at different flare levels and modeled the evolution of wafer CD through flare, reticle CD, and pitch using Brion's Tachyon OPC engine. The modeling first requires the generation of a flare map using long-range kernels to model the EUV specific long-range flare. The accuracy of the flare map can be established independently from the CD measurements, by using the traditional disappearing pad test for flare determination (Kirk test). The flare map is then used as background intensity in the calibration of the traditional optical models with short-range kernels. For a structure set of 600 features and over a flare range of 4-6%, an rms fit value of 0.9nm was obtained. As a second aspect of the modeling, we have calibrated a full resist model to process window data. The full resist model is then used in a combination with experimental measurements of reticle CD, slit intensity uniformity, focal plane behavior, and EUV thick mask effects to model the evolution of wafer CD across the exposure field. The modeled evolution of CD across the exposure field was found to be a good match to the experimentally seen evolution of CD across the field, and confirms that the 4 factors mentioned above are main contributions to the CD uniformity across the field. As such the modeling work enables a better understanding of the errors contributing to CD variation across the field for EUV technology.

Hendrickx, Eric; Lorusso, Gian F.; Jiang, Jiong; Chen, Luoqi; Liu, Wei; van Setten, Eelco; Hansen, Steve

2009-10-01

317

Microfluidics for Drug Delivery  

Microsoft Academic Search

Drug delivery, i.e. the way a pharmacologically active substance is delivered to the body, has a significant impact on the\\u000a therapeutic value of medication. The paper gives an overview on different drug delivery schemes and describes the limitations\\u000a of the oral route, which is the current gold standard in the market. Following these limitations, plenty of alternative (parenteral)\\u000a drug delivery

S. Haeberle; D. Hradetzky; A. Schumacher; M. Vosseler; S. Messner; R. Zengerle

318

Automatic identification of organ\\/tissue regions in CT image data for the implementation of patient specific phantoms for treatment planning in cancer therapy  

Microsoft Academic Search

In vivo targeted radiotherapy has the potential to be an effective treatment for many types of cancer. Agents which show preferred uptake by cancerous tissue are labeled with radio-nuclides and administered to the patient. The preferred uptake by the cancerous tissue allows for the delivery of therapeutically effective radiation absorbed doses to tumors, while sparing normal tissue. Accurate absorbed dose

Richard Blaine Sparks

1998-01-01

319

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.

Glide-Hurst, Carri K.

2014-01-01

320

Exploring Primary Care Providers' Interest in Using Patient Navigators to Assist in the Delivery of Tobacco Cessation Treatment to Low Income, Ethnic/Racial Minority Patients  

PubMed Central

We examined attitudes and practices regarding tobacco cessation interventions of primary care physicians serving low income, minority patients living in urban areas with a high smoking prevalence. We also explored barriers and facilitators to physicians providing smoking cessation counseling to determine the need for and interest in deploying a tobacco-focused patient navigator at community-based primary care practice sites. A self-administered survey was mailed to providers serving Medicaid populations in New York City’s Upper Manhattan and areas of the Bronx. Provider counseling practices were measured by assessing routine delivery (?80% of the time) of a brief tobacco cessation intervention (i.e., “5 A’s”). Provider attitudes were assessed by a decisional balance scale comprising 10 positive (Pros) and 10 negative (Cons) perceptions of tobacco cessation counseling. Of 254 eligible providers, 105 responded (41%). Providers estimated 22% of their patients currently use tobacco and nearly half speak Spanish. A majority of providers routinely asked about tobacco use (92%) and advised users to quit (82%), whereas fewer assisted in developing a quit plan (32%) or arranged follow-up (21%). Compared to providers reporting <80% adherence to the “5 A’s”, providers reporting ?80% adherence tended to have similar mean Pros and Cons scores for Ask, Advise, and Assess but higher Pros and lower Cons for Assist and Arrange. Sixty four percent of providers were interested in providing tobacco-related patient navigation services at their practices. Although most providers believe they can help patients quit smoking, they also recognize the potential benefit of having a patient navigator connect their patients with evidence-based cessation services in their community.

Lubetkin, Erica I.; Lu, Wei-Hsin; Krebs, Paul; Yeung, Howa; Ostroff, Jamie S.

2014-01-01

321

Accurate ab Initio Spin Densities  

PubMed Central

We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as a basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys.2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insight into chemically interesting features of the molecule under study such as the distribution of ? and ? electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput.2011, 7, 2740].

2012-01-01

322

Delivery technologies for human vaccines.  

PubMed

There is currently intense research activity aimed at the development of new delivery systems for vaccines. The goal is to identify optimal methods for presenting target antigens to the immune system in a manner that will elicit immune responses appropriate for protection against, or treatment of, a specific disease. Several different approaches to this general goal have been developed, some are empirical and remain poorly understood, others are more rational, being based, for example, on mimicking natural infections in vivo or on targeting particular features of the immune system. This article will review three categories of delivery systems: (i) adjuvants and formulations; (ii) antigen vectors, including live attenuated micro-organisms and synthetic vectors; and (iii) novel devices for vaccine administration. The review will be restricted to late stage developments in the field of human vaccination. PMID:12176848

Moingeon, Philippe; de Taisne, Charles; Almond, Jeffrey

2002-01-01

323

Validation and Analysis of a Mathematical Model of a Replication-competent Oncolytic Virus for Cancer Treatment: Implications for Virus Design and Delivery  

Microsoft Academic Search

Motivated by the rapid expansion in the development of replication- competent viral agents for the treatment of solid tumors, we formulated and analyzed a three-dimensional mathematical model of a tumor that is infected by a replication-competent virus. We initially considered three patterns of intratumoral injection in which a fixed fraction of cells are initially infected with the virus throughout (a)

Lawrence M. Wein; Joseph T. Wu; David H. Kirn

2003-01-01

324

Comparing Two Service Delivery Models for Homeless Individuals With Complex Behavioral Health Needs: Preliminary Data From Two SAMHSA Treatment for Homeless Studies  

Microsoft Academic Search

Assertive Community Treatment (ACT) and the Comprehensive, Continuous, Integrated System of Care (CCISC) are two models for delivering services to homeless persons with complex behavioral health needs. This quasi-experimental study presents preliminary data comparing these two programs. The first program was based out of a community mental health center and utilized the ACT model of care with supported housing (ACT-SH),

M. Scott Young; Colleen Clark; Kathleen Moore; Blake Barrett

2009-01-01

325

Oral Insulin Delivery: How Far Are We?  

PubMed Central

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

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

2013-01-01

326

High aspect ratio elongated microparticles for enhanced topical drug delivery in human volunteers.  

PubMed

Delivery of therapeutics into skin is hindered by the epidermal barriers. To overcome these barriers for the treatment of skin diseases, a cutaneous delivery method capable of field treatment using silica-elongated microparticles is developed. The microparticles are massaged into the skin using a 3D-printed microtextured applicator resulting in significant field-directed drug delivery enhancement. PMID:24421280

Raphael, Anthony P; Primiero, Clare A; Lin, Lynlee L; Smith, Ross Flewell; Dyer, Philip; Soyer, H Peter; Prow, Tarl W

2014-06-01

327

Development of a geometry-based respiratory motion-simulating patient model for radiation treatment dosimetry.  

PubMed

Temporal and spatial anatomical changes caused by respiration during radiation treatment delivery can lead to discrepancies between the prescribed and actually received radiation doses. This paper presents a study to construct a respiratory-motion-simulating, four-dimensional (4D) patient anatomical and dosimetry model for the study of dosimetric effects of organ motion on various radiation treatment plans and delivery strategies. A 3D VIP-Man (VIsible Photographic Man) model has been reconstructed using the Non-Uniform Rational B-Splines (NURBS) method to reflect the deformation of organs during respiration by manipulating surface control points as time-dependent equations. The 4D model is applied to dose simulation using the Monte Carlo code EGS4 (Electron Gamma Shower, version 4). Two delivery scenarios in radiation therapy were simulated: "gating" treatment and 4D "image-guided" treatment. For each delivery scenario, one conformal plan and one Intensity Modulated Radiation Therapy (IMRT) plan were developed. A lesion in the left lung was modeled to investigate the impact of respiratory motion on radiation dose distributions. Based on target dose volume histograms (DVHs), it is demonstrated that it is important to use accurate "gating" to improve the dose distribution. The results also suggest that, during a 4D "image-guided" treatment delivery, monitoring of patient breathing pattern is critical. This study demonstrates the potential of using "standard" motion-simulating patient model for 4D treatment planning and motion management. PMID:18449164

Zhang, Juying; Xu, George X; Shi, Chengyu; Fuss, Martin

2008-01-01

328

Development of a geometry-based respiratory motion-simulating patient model for radiation treatment dosimetry  

PubMed Central

Temporal and spatial anatomic changes caused by respiration during radiation treatment delivery can lead to discrepancies between prescribed and actual radiation doses. The present paper documents a study to construct a respiratory-motion-simulating, four-dimensional (4D) anatomic and dosimetry model for the study of the dosimetric effects of organ motion for various radiation treatment plans and delivery strategies. The non-uniform rational B-splines (NURBS) method has already been used to reconstruct a three-dimensional (3D) VIP-Man (“visible photographic man”) model that can reflect the deformation of organs during respiration by using time-dependent equations to manipulate surface control points. The EGS4 (Electron Gamma Shower, version 4) Monte Carlo code is then used to apply the 4D model to dose simulation. We simulated two radiation therapy delivery scenarios: gating treatment and 4D image-guided treatment. For each delivery scenario, we developed one conformal plan and one intensity-modulated radiation therapy plan. A lesion in the left lung was modeled to investigate the effect of respiratory motion on radiation dose distributions. Based on target dose–volume histograms, the importance of using accurate gating to improve the dose distribution is demonstrated. The results also suggest that, during 4D image-guided treatment delivery, monitoring of the patient’s breathing pattern is critical. This study demonstrates the potential of using a “standard” motion-simulating patient model for 4D treatment planning and motion management.

Zhang, Juying; Xu, X. George; Shi, Chengyu; Fuss, Martin

2009-01-01

329

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.

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

2014-01-01

330

Bioactive borate glass scaffolds: in vitro and in vivo evaluation for use as a drug delivery system in the treatment of bone infection  

Microsoft Academic Search

The objective of this work was to evaluate borate bioactive glass scaffolds (with a composition in the system Na2O–K2O–MgO–CaO–B2O3–P2O5) as devices for the release of the drug Vancomycin in the treatment of bone infection. A solution of ammonium phosphate,\\u000a with or without dissolved Vancomycin, was used to bond borate glass particles into the shape of pellets. The in vitro degradation

Xin Liu; Zongping Xie; Changqing Zhang; Haobo Pan; Mohamed N. Rahaman; Xin Zhang; Qiang Fu; Wenhai Huang

2010-01-01

331

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) [Livermore, CA; Squire, Dwight V. (Livermore, CA) [Livermore, CA; Robinson, Jeffrey A. (Manteca, CA) [Manteca, CA; House, Palmer A. (Walnut Creek, CA) [Walnut Creek, CA

2002-01-01

332

Ocular drug delivery.  

PubMed

Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

2010-09-01

333

Novel Drug Delivery System Shows Early Promise for Treating Lupus in Mice  

MedlinePLUS

... Drug Delivery System Shows Early Promise for Treating Lupus in Mice A drug delivery system using nanoparticle ... cells can potentially improve treatment approaches for systemic lupus erythematosus (SLE), according to research partially funded by ...

334

CNS drug delivery systems: novel approaches.  

PubMed

The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumours, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancers or heart diseases. The abysmally low number of potential therapeutics reaching commercial success is primarily due to the complexity of the CNS drug development. The clinical failure of many probable candidates is often, ascribable to poor delivery methods which do not pervade the unyielding BBB. It restricts the passive diffusion of many drugs into the brain and constitutes a significant obstacle in the pharmacological treatment of central nervous system (CNS) disorders. General methods that can enhance drug delivery to the brain are, therefore, of great pharmaceutical interest. Various strategies like non-invasive methods, including drug manipulation encompassing transformation into lipophilic analogues, prodrugs, chemical drug delivery, carrier-mediated drug delivery, receptor/vector mediated drug delivery and intranasal drug delivery, which exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain, are widely used. On the other hand the invasive methods which primarily rely on disruption of the BBB integrity by osmotic or biochemical means, or direct intracranial drug delivery by intracerebroventricular, intracerebral or intrathecal administration after creating reversible openings in the head, are recognised. Extensive review pertaining specifically, to the patents relating to drug delivery across the CNS is currently available. However, many patents e.g. US63722506, US2002183683 etc., have been mentioned in a few articles. It is the objective of this article to expansively review drug delivery systems for CNS by discussing the recent patents available. PMID:19149731

Pathan, Shadab A; Iqbal, Zeenat; Zaidi, Syed M A; Talegaonkar, Sushma; Vohra, Divya; Jain, Gaurav K; Azeem, Adnan; Jain, Nitin; Lalani, Jigar R; Khar, Roop K; Ahmad, Farhan J

2009-01-01

335

Colon delivery of prednisolone based on chitosan coated polysaccharide tablets  

Microsoft Academic Search

Colon drug delivery is advantageous in the treatment of colonic disease and oral delivery of drugs unstable or suceptible\\u000a to enzymatic degradation in upper Gl tract. In this study, multilayer coated system that is resistant to gastric and small\\u000a intestinal conditions but can be easily degraded by colonic bacterial enzymes was designed to achieve effective colon delivery\\u000a of prednisolone. Variously

Hyun-Sun Park; Jue-Yeon Lee; Sun-Hye Cho; Hyon-Jin Baek; Seung-Jin Lee

2002-01-01

336

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.

Devi, V. Kusum; Jain, Nimisha; Valli, Kusum S.

2010-01-01

337

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects  

PubMed Central

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAILDR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAILDR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments.

Yu, R; Deedigan, L; Albarenque, S M; Mohr, A; Zwacka, R M

2013-01-01

338

A generalized a priori dose uncertainty model of IMRT delivery.  

PubMed

Multileaf collimator-based intensity modulated radiation therapy (IMRT) is complex because each intensity modulated field consists of hundreds of subfields, each of which is associated with an intricate interplay of uncertainties. In this study, the authors have revised the previously introduced uncertainty model to provide an a priori accurate prediction of dose uncertainty during treatment planning in IMRT. In the previous model, the dose uncertainties were categorized into space-oriented dose uncertainty (SOU) and nonspace-oriented dose uncertainty (NOU). The revised model further divided the uncertainty sources into planning and delivery. SOU and NOU associated with a planning system were defined as inherent dose uncertainty. A convolution method with seven degrees of freedom was also newly applied to generalize the model for practical clinical cases. The model parameters were quantified through a set of measurements, accumulated routine quality assurance (QA) data, and peer-reviewed publications. The predicted uncertainty maps were compared with dose difference distributions between computations and 108 simple open-field measurements using a two-dimensional diode array detector to verify the validity of the model parameters and robustness of the generalized model. To examine the applicability of the model to overall dose uncertainty prediction in IMRT, a retrospective analysis of QA measurements using the diode array detector for 32 clinical IM fields was also performed. A scatter diagram and a correlation coefficient were employed to investigate a correlation of the predicted dose uncertainty distribution with the dose discrepancy distribution between calculation and delivery. In addition, a gamma test was performed to correlate failed regions in dose verification with the dose uncertainty map. The quantified model parameters well correlated the predicted dose uncertainty with the probable dose difference between calculations and measurements. It was visually validated with the scatter diagrams. The average correlation coefficient between uncertainty and dose difference of 108 verification measurements was 0.80 +/- 0.04, indicating a strong linear correlation. In the clinical IM field studies, the dose uncertainty map mimicked the probable dose difference distribution. The average correlation coefficient between the overall dose uncertainty and the dose difference of 32 QA measurements (total 13 184 comparison points) was 0.75 +/- 0.07, which also indicated a strong linear correlation between them. The failed regions of the gamma test remarkably corresponded to relatively high dose uncertainty. In conclusion, the dose uncertainty map was able to highlight high dose uncertainty regions, where more care should be taken during the treatment plan. The a priori accurate prediction of dose uncertainty in IMRT will significantly improve the treatment plan evaluation process, thus improving the quality of radiation treatments. PMID:18404934

Jin, Hosang; Palta, Jatinder; Suh, Tae-Suk; Kim, Siyong

2008-03-01

339

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.

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

2014-01-01

340

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.

Godsey, Megan E; Suryaprakash, Smruthi; Leong, Kam W

2014-01-01

341

[Haemorrhage delivery. About 65 cases].  

PubMed

The delivery haemorrhage is actually a problem of public health. It is responsible of 31.5 % of the maternal death in Tunisia. The goal of this work is to study the frequency of this complication, its gravity, its risk factors, its etiologists and its methods of treatment. It is a retrospective study. of 65 cases of delivery haemorrhage recorded to the obstetric gynaecology service "C" of the centre of motherhood and neonatology of Tunis during 4 years. The frequency of the delivery haemorrhage in our study is 1.19%. The middle age of the patient is of 31 years. Their middle parity is 2.4. Factors of risk taking out again our set are: gestational toxemia (35.4%), primiparity (33.8%), advanced maternal age (30.7%), pre-existent anaemia (24.6%). the uterine surdistension (21.3%), an abnormal middle length of labour (69.6%). use of oxytocin during labour (34%), induction (21.5%). Etiologists in our set are: atone in 63% of cases, retained placenta in 31.2% des cases, coagulopathie (9.2%), placenta previa (1.5%), uterine inversion (1.5%). The hold must be in charge multidisciplinary, systematized, precocious and dynamic. PMID:16915778

Ben Hmid, Rim; El Houssaini, Sonia; Mahjoub, Sami; Mourali, Mecheal; Zeghal, Dorra; Zouari, Faouzia; El Kamel, Moez; Bouchnek, Mourad; Maghrebi, Hayen

2006-05-01

342

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.

Nichols, Scott P.; Storm, Wesley L.; Koh, Ahyeon; Schoenfisch, Mark H.

2012-01-01

343

Gene Expression Profiling Can Accurately Diagnose Burkitt's Lymphoma  

Cancer.gov

Gene profiling, a molecular technique that examines many genes simultaneously, can accurately distinguish between two types of immune cell tumors, Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL). Burkitt's lymphoma and DLBCL appear similar when viewed under a microscope but correct diagnosis is critical because each requires very different treatments.

344

Proton treatment room concepts for precision and efficiency.  

PubMed

Proton radiation therapy involves accurate delivery of proton beams to targets inside the body without direct visual control of the internal anatomy. Targeting of the tumor and avoidance of critical structures within the patient have to be both accurate and precise to achieve the desired therapeutic results. Good understanding of proton radiation delivery and patient alignment concepts in the treatment room is essential to achieve this goal. This overview article presents treatment room concepts that will ensure precise proton beam delivery and, at the same time, guarantee an efficient patient throughput. Concepts discussed include effective patient immobilization, image-guided alignment verification, appropriate training of radiotherapists, and the physician's integrative role in understanding the complex spatial relationships between tumor, organs at risk, treatment beam configuration, and application of proton radiation dose. It will be demonstrated that in addition to the technical armamentarium, now commonplace in modern radiation oncology departments, the interaction between radiation oncologist, medical physicist and radiotherapist is important for efficient operation of a proton treatment facility. PMID:17668953

Schulte, Reinhard W

2007-08-01

345

Novel gene delivery systems  

PubMed Central

Gene therapy is an emerging field in medical and pharmaceutical sciences because of its potential in treating chronic diseases like cancer, viral infections, myocardial infarctions, and genetic disorders. Application of gene therapy is limited because of lack of suitable methods for proper introduction of genes into cells and therefore, this is an area of interest for most of the researchers. To achieve successful gene therapy, development of proper gene delivery systems could be one of the most important factors. Several nonviral and viral gene transfer methods have been developed. Even though the viral agents have a high transferring efficiency, they are difficult to handle due to their toxicity. To overcome the safety problems of the viral counterpart, several nonviral in vitro and in vivo gene delivery systems are developed. Out of these, the most promising and latest systems include polymer-based nonviral gene carriers, dendrimers, and physical means like electroporation, microinjection, etc., Shunning of possible immunogenicity and toxicity, and the feasibility of repeated administration are some of the merits of nonviral gene delivery systems over viral gene delivery. An ideal nonviral gene carrying system should possess all these merits without any compromise to its gene transferring efficiency. The viral gene delivery systems include lytic and nonlytic vectors for drug delivery. Inspite of its toxicity they are still preferred because of their long term expression, stability, and integrity. This review explores the recent developments and relevancy of the novel gene delivery systems in gene therapy.

Manjila, Steffy B; Baby, Jomon N; Bijin, Elambilan N; Constantine, Icey; Pramod, Kannissery; Valsalakumari, Janardhanan

2013-01-01

346

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.

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

347

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.

Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

2014-01-01

348

What is an acceptably smoothed fluence? Dosimetric and delivery considerations for dynamic sliding window IMRT  

PubMed Central

Background The study summarised in this report aimed to investigate the interplay between fluence complexity, dose calculation algorithms, dose calculation spatial resolution and delivery characteristics (monitor units, effective field width and dose delivery against dose prediction agreement) was investigated. A sample set of complex planning cases was selected and tested using a commercial treatment planning system capable of inverse optimisation and equipped with tools to tune fluence smoothness. Methods A set of increasingly smoothed fluence patterns was correlated to a generalised expression of the Modulation Index (MI) concept, in nature independent from the specific planning system used that could therefore be recommended as a predictor to score fluence "quality" at a very early stage of the IMRT QA process. Fluence complexity was also correlated to delivery accuracy and characteristics in terms of number of MU, dynamic window width and agreement between calculation and measurement (expressed as percentage of field area with a ? > 1 (%FA)) when comparing calculated vs. delivered modulated dose maps. Different resolutions of the calculation grid and different photon dose algorithms (pencil beam and anisotropic analytical algorithm) were used for the investigations. Results and Conclusion i) MI can be used as a reliable parameter to test different approaches/algorithms to smooth fluences implemented in a TPS, and to identify the preferable default values for the smoothing parameters if appropriate tools are implemented; ii) a MI threshold set at MI < 19 could ensure that the planned beams are safely and accurately delivered within stringent quality criteria; iii) a reduction in fluence complexity is strictly correlated to a corresponding reduction in MUs, as well as to a decrease of the average sliding window width (for dynamic IMRT delivery); iv) a smoother fluence results in a reduction of dose in the healthy tissue with a potentially relevant clinical benefit; v) increasing the smoothing parameter s, MI decreases with %FA: fluence complexity has a significant impact on the accuracy of delivery and the agreement between calculation and measurements improves with the advanced algorithms.

Giorgia, Nicolini; Antonella, Fogliata; Eugenio, Vanetti; Alessandro, Clivio; Filippo, Ammazzalorso; Luca, Cozzi

2007-01-01

349

Microsponge delivery system.  

PubMed

Microsponges are polymeric delivery systems consisting of porous microspheres having a size range in between 5 to 300 microm depending upon the degree of smoothness or after feel required for the end formulations. Microsponge Delivery System MDS is a unique technology for controlled delivery of drug. The present review introduces Microsponge technology along with its synthesis, characterization, programmable parameters and release mechanism of MDS. Wide ranges of applications are also suggested to develop drug or cosmetic products with enhanced safety and efficacy. MDS can provide increased efficacy for topically active agents with enhanced safety, extended product stability and improved aesthetic properties in an efficient and novel manner. PMID:17456031

Chadawar, Vikrant; Shaji, Jessy

2007-04-01

350

Neurotrophin delivery using nanotechnology.  

PubMed

Deficits or overexpression of neurotrophins cause neurodegenerative diseases and psychiatric disorders. These proteins are required for the maintenance of the function, plasticity and survival of neurons in the central (CNS) and peripheral nervous systems. Significant efforts have been devoted to developing therapeutic delivery systems that enable control of neurotrophin dosage in the brain. Here, we suggest that nanoparticulate carriers favoring targeted delivery in specific brain areas and minimizing biodistribution to the systemic circulation should be developed toward clinical benefits of neuroregeneration. We also provide examples of improved targeted neurotrophin delivery to localized areas in the CNS. PMID:23891881

Angelova, Angelina; Angelov, Borislav; Drechsler, Markus; Lesieur, Sylviane

2013-12-01

351

Tripartite complex for axonal transport drug delivery achieves pharmacological effect  

Microsoft Academic Search

BACKGROUND: Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy

Aaron G Filler; Garth T Whiteside; Mark Bacon; Martyn Frederickson; Franklyn A Howe; Miri D Rabinowitz; Alan J Sokoloff; Terrence W Deacon; Chris Abell; Raj Munglani; John R Griffiths; B Anthony Bell; Andrew ML Lever

2010-01-01

352

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

353

Novel drug delivery systems for glaucoma.  

PubMed

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

2011-05-01

354

Phase Composition Control of Calcium Phosphate Nanoparticles for Tunable Drug Delivery Kinetics and Treatment of Osteomyelitis. Part 2: Antibacterial and Osteoblastic Response  

PubMed Central

Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of the previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release time scales on bacterial and osteoblastic cell cultures. All CAP powders exhibited satisfying antibacterial performance against Staphylococcus aureus, the main causative agent of osteomyelitis. Still, owing to its highest drug adsorption efficiency, the most bacteriostatically effective phase was amorphous CAP with the minimal inhibitory concentration of less than 1 mg/ml. At the same time, the positive cell response and osteogenic effect of the antibiotic-loaded CAP particles was confirmed in vitro for all the sparsely soluble CAP phases. Adsorption of the antibiotic onto CAP particles reversed the deleterious effect that the pure antibiotic exerted on the osteogenic activity of the osteoblastic cells. The simultaneous osteogenic and antimicrobial performance of the material developed in this study, altogether with its ability to exhibit sustained drug release, may favor its consideration as a material base for alternative therapeutic approaches to prolonged antibiotic administration and surgical debridement typically prescribed in the treatment of osteomyelitis.

Uskokovic, Vuk; Desai, Tejal A.

2012-01-01

355

Insulin Delivery System.  

National Technical Information Service (NTIS)

Aspects of the disclosure generally relate to insulin delivery systems and compositions having a insulin secreting .beta. cell line or insulin secreting recombinant non-.beta. cells sequestered in a glucose-responsive material. The disclosed insulin deliv...

A. Sambanis S. Y. Cheng

2005-01-01

356

Implantable Insulin Delivery System.  

National Technical Information Service (NTIS)

An insulin delivery system suitable for experimental implants and external use has been developed to study glucose control for diabetics. The programmable system developed at Sandia National Laboratories, in conjunction with the University of New Mexico S...

J. T. Love J. I. Gaona

1981-01-01

357

Project Delivery Methods.  

ERIC Educational Resources Information Center

Describes project delivery methods that are replacing the traditional Design/Bid/Build linear approach to the management, design, and construction of new facilities. These variations can enhance construction management and teamwork. (SLD)

Dolan, Thomas G.

2003-01-01

358

A review of the gastrointestinal therapeutic system (GITS) formulation and its effectiveness in the delivery of antihypertensive drug treatment (focus on nifedipine GITS)  

PubMed Central

Hypertension treatment guidelines do not discriminate within drug classes and, furthermore, do not consider whether or not all of the formulations of any given drug licensed for once-daily administration can be considered to be therapeutically interchangeable. This article focuses on this issue with respect to nifedipine and the development of the gastrointestinal therapeutic system (GITS) formulation. Nifedipine GITS is regarded as the gold standard once-daily formulation of nifedipine and, as such, it is anticipated that alternative formulations will be therapeutically equivalent to nifedipine GITS. In general, this depends on demonstrating pharmacokinetic bioequivalence. This article is intended to focus attention on generic substitution and, in particular, on aspects of the scientific basis for the substitution of generic products in place of branded products. Such substitution is required for cost-saving or cost-containment reasons and is justified on the basis that the generic (substitute) drug is “therapeutically” equivalent to the branded drug. Unfortunately, there are serious shortcomings in the current methods of assessment insofar as they are typically based on statistical comparisons of average pharmacokinetic parameter values, using arbitrary comparative criteria. This article illustrates the shortcomings of the current approaches to generic substitution and concludes that, in regulatory terms, either more rigorous pharmacokinetic criteria are required or pharmacodynamic indices should be added to reinforce the regulatory criteria. Generic substitution is a balancing act but, at the moment, the cost issue is dominant. To restore the balance, equivalent efficacy must be confirmed. At present, therefore, in the absence of such regulatory rigor, the obvious course is to prefer the branded product, the therapeutic efficacy of which (including outcome benefits) has been established.

Meredith, Peter A; Elliott, Henry L

2013-01-01

359

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

360

Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo - Part II: Rheological characterization and in vivo assessment through dermatopharmacokinetic and pilot clinical studies.  

PubMed

Vitiligo is a non contagious acquired pigmentation disorder with limited treatment possibilities. Clobetasol propionate (CP) is the drug-of-choice for vitiligo which suppresses the immune system by reducing immunoglobulin action and causes the restoration of melanocytes leading to repigmentation of skin. However, despite being effective, its low and variable bioavailability prompt for development of novel carrier that could effectively target CP to site of action without producing undesirable side-effects. Low solubility of CP in subsequent poor in vivo bioavailability was overcome by formulating microemulsion based gel of CP (MBC) which would enhance the percutaneous transport of CP into and across the skin barrier. Comprehensive characterization of MBC was carried out for viscosity, gel strength and rheological behavior. In vitro studies revealed much higher drug release, skin penetration and enhanced skin accumulation as compared to control (Cream of CP). In vitro and in vivo occlusion studies demonstrated similar occlusiveness for MBC and control. MBC exhibited 3.16 times higher stratum corneum CP levels compared to control. Visualization of cutaneous uptake in vivo using laser scanning microscopy confirmed targeting of CP to epidermis and dermis. Dermatopharmacokinetic studies of MBC showed enhanced drug deposition of CP in skin layers. MBC was assessed for in vivo efficacy by single blind randomized pilot clinical study. The efficacy was assessed by vitiligo area scoring index (VASI) method. After completion of trial, repigmentation of vitiligo patches in patients were evaluated and scored. MBC was superior in terms of faster repigmentation and efficacy when compared with control (p value<0.5). Hence, it was concluded that CP loaded MBC possess enhanced skin localization as well as therapeutic activity in vitiligo patients. PMID:24767976

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

2014-07-01

361

Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain.  

PubMed

Several treatment modalities for neurodegenerative diseases or tumors of the central nervous system involve invasive delivery of large molecular weight drugs to the brain. Despite the ample record of experimental studies, accurate drug targeting for the human brain remains a challenge. This paper proposes a systematic design method of administering drugs to specific locations in the human brain based on first principles transport in porous media. The proposed mathematical framework predicts achievable treatment volumes in target regions as a function of brain anatomy and infusion catheter position. A systematic procedure to determine the optimal infusion and catheter design parameters that maximize the penetration depth and volumes of distribution will be discussed. The computer simulations are validated with agarose gel phantom experiments and rat data. The rigorous computational approach will allow physicians and scientists to better plan the administration of therapeutic drugs to the central nervous system. PMID:18713700

Linninger, Andreas A; Somayaji, Mahadevabharath R; Zhang, Libin; Smitha Hariharan, Madhu; Penn, Richard D

2008-09-01

362

Accurate, reproducible measurement of blood pressure.  

PubMed Central

The diagnosis of mild hypertension and the treatment of hypertension require accurate measurement of blood pressure. Blood pressure readings are altered by various factors that influence the patient, the techniques used and the accuracy of the sphygmomanometer. The variability of readings can be reduced if informed patients prepare in advance by emptying their bladder and bowel, by avoiding over-the-counter vasoactive drugs the day of measurement and by avoiding exposure to cold, caffeine consumption, smoking and physical exertion within half an hour before measurement. The use of standardized techniques to measure blood pressure will help to avoid large systematic errors. Poor technique can account for differences in readings of more than 15 mm Hg and ultimately misdiagnosis. Most of the recommended procedures are simple and, when routinely incorporated into clinical practice, require little additional time. The equipment must be appropriate and in good condition. Physicians should have a suitable selection of cuff sizes readily available; the use of the correct cuff size is essential to minimize systematic errors in blood pressure measurement. Semiannual calibration of aneroid sphygmomanometers and annual inspection of mercury sphygmomanometers and blood pressure cuffs are recommended. We review the methods recommended for measuring blood pressure and discuss the factors known to produce large differences in blood pressure readings.

Campbell, N R; Chockalingam, A; Fodor, J G; McKay, D W

1990-01-01

363

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 ...

364

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

365

Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery  

PubMed Central

Periodontal pockets act as a natural reservoir filled with gingival crevicular fluid for the controlled release delivery of antimicrobials directly. This article reflects the present status of nonsurgical controlled local intrapocket delivery of antimicrobials in the treatment of periodontitis. These sites have specialty in terms of anatomy, permeability, and their ability to retain a delivery system for a desired length of time. A number of antimicrobial products and the composition of the delivery systems, its use, clinical results, and their release are summarized. The goal in using an intrapocket device for the delivery of an antimicrobial agent is the achievement and maintenance of therapeutic drug concentration for the desired period of time. Novel controlled drug delivery system are capable of improving patient compliance as well as therapeutic efficacy with precise control of the rate by which a particular drug dosage is released from a delivery system without the need for frequent administration. These are considered superior drug delivery system because of low cost, greater stability, non-toxicity, biocompatibility, non-immunogenicity, and are biodegradable in nature. This review also focus on the importance and ideal features of periodontal pockets as a drug delivery platform for designing a suitable dosage form along with its potential advantage and limitations. The microbes in the periodontal pocket could destroy periodontal tissues, and a complete knowledge of these as well as an ideal treatment strategy could be helpful in treating this disease.

Nair, Sreeja C.; Anoop, K. R.

2012-01-01

366

FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY  

PubMed Central

Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized.

Liu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan

2010-01-01

367

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

368

Improving substance abuse data systems to measure `waiting time to treatment': Lessons learned from a quality improvement initiative  

PubMed Central

Robust data measurement systems assess health care performance and monitor population-level treatment trends. A key challenge in the assessment of substance abuse treatment is the development of systems to accurately monitor service delivery indicators. Wait time to treatment, as defined by the days between first request for service and first treatment, is an important measure of organizational process and delivery of care. The Network for the Improvement of Addiction Treatment emphasizes wait time as a primary outcome in their study of 201 addiction treatment agencies in the USA. This article describes the changes made in five state data systems to monitor wait times and outlines lessons learned that could be applied to other health data tracking systems.

Hoffman, Kim A; Quanbeck, Andrew; Ford, James H; Wrede, Fritz; Wright, Dagan; Lambert-Wacey, Dawn; Chvojka, Phil; Hanchett, Andrew; McCarty, Dennis

2012-01-01

369

Prediction of convection-enhanced drug delivery to the human brain.  

PubMed

The treatment for many neurodegenerative diseases of the central nervous system (CNS) involves the delivery of large molecular weight drugs to the brain. The blood brain barrier, however, prevents many therapeutic molecules from entering the CNS. Despite much effort in studying drug dispersion with animal models, accurate drug targeting in humans remains a challenge. This article proposes an engineering approach for the systematic design of targeted drug delivery into the human brain. The proposed method predicts achievable volumes of distribution for therapeutic agents based on first principles transport and chemical kinetics models as well as accurate reconstruction of the brain geometry from patient-specific diffusion tensor magnetic resonance imaging. The predictive capabilities of the methodology will be demonstrated for invasive intraparenchymal drug administration. A systematic procedure to determine the optimal infusion and catheter design parameters to maximize penetration depth and volumes of distribution in the target area will be discussed. The computational results are validated with agarose gel phantom experiments. The methodology integrates interdisciplinary expertise from medical imaging and engineering. This approach will allow physicians and scientists to design and optimize drug administration in a systematic fashion. PMID:17950757

Linninger, Andreas A; Somayaji, Mahadevabharath R; Mekarski, Megan; Zhang, Libin

2008-01-01

370

Imaging Drug Delivery and Drug Responses in the Lung  

Microsoft Academic Search

Conventional two-dimensional and three-dimensional single pho- ton emission computed tomography and positron emission tomog- raphy imaging tools and specific inhaled radiotracers allow accurate and reliable measurements of drug delivery to the lung. Pharmaco- kinetics and patterns of drug distribution can be monitored over time. In addition, physiologic measurements of ventilation, perfu- sion, mucociliary clearance, inflammation, and respiratory absorp- tion can

Myrna Dolovich; Renee Labiris

2004-01-01

371

Evaluating water delivery in tertiary units Part l: Method  

Microsoft Academic Search

In most irrigated areas, the present desire for rehabilitation raises the need for an accurate analysis of the actual situation. We present a new method to evaluate the quality of water delivery and the origin of water deficits (and irrigation water losses) in an irrigated area, based on the simultaneous analysis of distribution rules and actual irrigation events. First, a

Luc Gilot

1997-01-01

372

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

373

9F-4 Rectangular Cymbal Arrays for Ultrasonic Transdermal Insulin Delivery  

Microsoft Academic Search

Studies have shown that ultrasound mediated transdermal drug delivery offers a promising potential for needle-less insulin delivery for diabetes treatment. Arrays of cymbal transducers have been shown to be effective in delivering therapeutic levels of insulin to decrease hyperglycemic glucose levels in rats, rabbits and pigs. To improve delivery efficiency of the cymbal arrays, an increase in the spatial intensity

Joseph Luis; Eun-Joo Park; Richard J. Meyer Jr; Nadine Barrie Smith

2007-01-01