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Sample records for accurate treatment delivery

  1. Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery

    PubMed Central

    Engelsman, M.; Lu, H.-M.; Herrup, D.; Bussiere, M.; Kooy, H. M.

    2009-01-01

    Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output. PMID:19610306

  2. [Myasthenia gravis - optimal treatment and accurate diagnosis].

    PubMed

    Gilhus, Nils Erik; Kerty, Emilia; Løseth, Sissel; Mygland, Åse; Tallaksen, Chantal

    2016-07-01

    Around 700 people in Norway have myasthenia gravis, an autoimmune disease that affects neuromuscular transmission and results in fluctuating weakness in some muscles as its sole symptom. The diagnosis is based on typical symptoms and findings, detection of antibodies and neurophysiological examination. Symptomatic treatment with acetylcholinesterase inhibitors is generally effective, but most patients also require immunosuppressive drug treatment. Antigen-specific therapy is being tested in experimental disease models. PMID:27381787

  3. The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

    SciTech Connect

    Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A.; Sheng, Ke

    2015-11-15

    Purpose: Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. Methods: A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. Results: The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was

  4. Controlled drug delivery in the treatment of diabetes mellitus.

    PubMed

    Irsigler, K; Kritz, H; Lovett, R G

    1985-01-01

    Diabetes not only requires correction of an insulin deficiency but it also demands adequate insulin delivery. A short historical review is given over the first 60 years of insulin treatment, where emphasis was mainly on the correction of insulin deficiency. Despite concerted efforts, metabolic results were often poor, and there was a high incidence of late complications, which will be described briefly. A major aim of new treatment approaches, which emphasizes better routes of insulin delivery, is the prevention or reversal of these late complications. Closed-loop systems are infusion systems located outside the body which deliver insulin according to glucose values that are measured continuously. The state of the art for such systems will be described with examples of clinical applications and results. These systems aid and stimulate research, but offer no long-term application for treatment. Open-loop systems are portable, both external and implantable, and lack an accurate glucose sensor so that the loop can be closed. A number of insulin delivery systems have been developed in this category ranging from highly complex, fully implantable units, programable from outside, to simple basal-rate infusion pumps. Various pumps are designed to be used with varying delivery routes, and the evaluation of different routes will be a vital topic in this article. Pros and cons of the intravenous, intraperitoneal, and subcutaneous routes will be discussed, with supporting research referenced. Clinical experience will be cited for both the complex and the simple infusion systems. Other topics to be covered include feasibility of long-term treatment, complications of this new treatment approach, guidelines for patient instruction and supervision, requirements for treatment of large patient groups with pumps in a modern diabetes center, requirements for the physician, the influence of improved metabolic control on late complications (prevention or regression), the possibility for

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

    SciTech Connect

    Yang, D; Li, X; Li, H; Wooten, H; Green, O; Rodriguez, V; Mutic, S

    2014-06-15

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

  6. Production of pure quasi-monochromatic 11C beams for accurate radiation therapy and dose delivery verification

    NASA Astrophysics Data System (ADS)

    Lazzeroni, Marta; Brahme, Anders

    2015-09-01

    In the present study we develop a new technique for the production of clean quasi-monochromatic 11C positron emitter beams for accurate radiation therapy and PET-CT dose delivery imaging and treatment verification. The 11C ion beam is produced by projectile fragmentation using a primary 12C ion beam. The practical elimination of the energy spread of the secondary 11C fragments and other beam contaminating fragments is described. Monte Carlo calculation with the SHIELD-HIT10+ code and analytical methods for the transport of the ions in matter are used in the analysis. Production yields, as well as energy, velocity and magnetic rigidity distributions of the fragments generated in a cylindrical target are scored as a function of the depth within 1 cm thick slices for an optimal target consisting of a fixed 20 cm section of liquid hydrogen followed by a variable thickness section of polyethylene. The wide energy and magnetic rigidity spread of the 11C ion beam can be reduced to values around 1% by using a variable monochromatizing wedge-shaped degrader in the beam line. Finally, magnetic rigidity and particle species selection, as well as discrimination of the particle velocity through a combined Time of Flight and Radio Frequency-driven Velocity filter purify the beam from similar magnetic rigidity contaminating fragments (mainly 7Be and 3He fragments). A beam purity of about 99% is expected by the combined method.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Gated Treatment Delivery Verification With On-Line Megavoltage Fluoroscopy

    SciTech Connect

    Tai An; Christensen, James D.; Gore, Elizabeth; Khamene, Ali; Boettger, Thomas; Li, X. Allen

    2010-04-15

    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.

  9. Accurate treatment of spontaneous polarization in III-nitrides

    NASA Astrophysics Data System (ADS)

    Dreyer, Cyrus E.; Janotti, Anderson; van de Walle, Chris G.

    2015-03-01

    The III-nitride compounds assume the wurtzite crystal structure in the ground state and therefore exhibit spontaneous and piezoelectric dipole moments in the c direction. Discontinuities in these moments at heterostructure interfaces result in electric fields in the layers, which can be detrimental because they separate electrons and holes in quantum wells. Accurate values for polarization differences are critical for understanding and engineering III-nitride heterostructures. Direct experimental measurement of spontaneous polarization has not been possible to date, and calculations are complicated by the necessity to choose a reference structure. The universal choice of reference structure for wurtzite has been zincblende; we demonstrate that this choice does not allow consistent determination of the differences of spontaneous polarizations between materials, which determine their physical manifestation. Using first-principles techniques based on hybrid density functional theory, we have determined polarization discontinuities using a consistent reference based on the hexagonal layered structure of these materials. We will discuss the results in light of available experimental data, and outline consequences for device simulations. Work supported by DOE.

  10. Translation research: from accurate diagnosis to appropriate treatment

    PubMed Central

    Webb, Craig P; Pass, Harvey I

    2004-01-01

    This review article focuses on the various aspects of translational research, where research on human subjects can ultimately enhance the diagnosis and treatment of future patients. While we will use specific examples relating to the asbestos related cancer mesothelioma, it should be stressed that the general approach outlined throughout this review is readily applicable to other diseases with an underlying molecular basis. Through the integration of molecular-based technologies, systematic tissue procurement and medical informatics, we now have the ability to identify clinically applicable "genotype"-"phenotype" associations across cohorts of patients that can rapidly be translated into useful diagnostic and treatment strategies. This review will touch on the various steps in the translational pipeline, and highlight some of the most essential elements as well as possible roadblocks that can impact success of the program. Critical issues with regard to Institutional Review Board (IRB) and Health Insurance Portability and Accountability Act (HIPAA) compliance, data standardization, sample procurement, quality control (QC), quality assurance (QA), data analysis, preclinical models and clinical trials are addressed. The various facets of the translational pipeline have been incorporated into a fully integrated computational system, appropriately named Dx2Tx. This system readily allows for the identification of new diagnostic tests, the discovery of biomarkers and drugable targets, and prediction of optimal treatments based upon the underlying molecular basis of the disease. PMID:15496233

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

    SciTech Connect

    Able, Charles M.; Bright, Megan; Frizzell, Bart

    2013-03-01

    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.

  12. SU-E-T-475: An Accurate Linear Model of Tomotherapy MLC-Detector System for Patient Specific Delivery QA

    SciTech Connect

    Chen, Y; Mo, X; Chen, M; Olivera, G; Parnell, D; Key, S; Lu, W; Reeher, M; Galmarini, D

    2014-06-01

    Purpose: An accurate leaf fluence model can be used in applications such as patient specific delivery QA and in-vivo dosimetry for TomoTherapy systems. It is known that the total fluence is not a linear combination of individual leaf fluence due to leakage-transmission, tongue-and-groove, and source occlusion effect. Here we propose a method to model the nonlinear effects as linear terms thus making the MLC-detector system a linear system. Methods: A leaf pattern basis (LPB) consisting of no-leaf-open, single-leaf-open, double-leaf-open and triple-leaf-open patterns are chosen to represent linear and major nonlinear effects of leaf fluence as a linear system. An arbitrary leaf pattern can be expressed as (or decomposed to) a linear combination of the LPB either pulse by pulse or weighted by dwelling time. The exit detector responses to the LPB are obtained by processing returned detector signals resulting from the predefined leaf patterns for each jaw setting. Through forward transformation, detector signal can be predicted given a delivery plan. An equivalent leaf open time (LOT) sinogram containing output variation information can also be inversely calculated from the measured detector signals. Twelve patient plans were delivered in air. The equivalent LOT sinograms were compared with their planned sinograms. Results: The whole calibration process was done in 20 minutes. For two randomly generated leaf patterns, 98.5% of the active channels showed differences within 0.5% of the local maximum between the predicted and measured signals. Averaged over the twelve plans, 90% of LOT errors were within +/−10 ms. The LOT systematic error increases and shows an oscillating pattern when LOT is shorter than 50 ms. Conclusion: The LPB method models the MLC-detector response accurately, which improves patient specific delivery QA and in-vivo dosimetry for TomoTherapy systems. It is sensitive enough to detect systematic LOT errors as small as 10 ms.

  13. Mathematical model accurately predicts protein release from an affinity-based delivery system.

    PubMed

    Vulic, Katarina; Pakulska, Malgosia M; Sonthalia, Rohit; Ramachandran, Arun; Shoichet, Molly S

    2015-01-10

    Affinity-based controlled release modulates the delivery of protein or small molecule therapeutics through transient dissociation/association. To understand which parameters can be used to tune release, we used a mathematical model based on simple binding kinetics. A comprehensive asymptotic analysis revealed three characteristic regimes for therapeutic release from affinity-based systems. These regimes can be controlled by diffusion or unbinding kinetics, and can exhibit release over either a single stage or two stages. This analysis fundamentally changes the way we think of controlling release from affinity-based systems and thereby explains some of the discrepancies in the literature on which parameters influence affinity-based release. The rate of protein release from affinity-based systems is determined by the balance of diffusion of the therapeutic agent through the hydrogel and the dissociation kinetics of the affinity pair. Equations for tuning protein release rate by altering the strength (KD) of the affinity interaction, the concentration of binding ligand in the system, the rate of dissociation (koff) of the complex, and the hydrogel size and geometry, are provided. We validated our model by collapsing the model simulations and the experimental data from a recently described affinity release system, to a single master curve. Importantly, this mathematical analysis can be applied to any single species affinity-based system to determine the parameters required for a desired release profile. PMID:25449806

  14. Drug delivery strategies for the treatment of Helicobacter pylori infections.

    PubMed

    Conway, B R

    2005-01-01

    Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated. PMID:15777232

  15. Pulmonary embolism during delivery--treatment and outcome.

    PubMed

    Zamurović, M; Damnjanović, D

    2015-01-01

    Pulmonary embolism during delivery is not a frequent occurrence. It is often impossible to ascertain whether it is a case of embolism by amniotic fluid or thromboembolism. Diagnostics of pulmonary embolism in labor is based solely on clinical symptoms. Immediate interdisciplinary treatment with cardiopulmonary resuscitation, hemodynamic stabilization, and correction of haemostasis disorders play a decisive role in prognosis. This paper presents diagnostics, treatment, and consequences of pulmonary embolism in expulsion phase during delivery in epidural anesthesia of a multiparous patient aged 37. PMID:26753499

  16. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

    PubMed Central

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

    2014-01-01

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

  17. Intelligent Nanoparticles for Advanced Drug Delivery in Cancer Treatment

    PubMed Central

    Spencer, David S.; Puranik, Amey S.; Peppas, Nicholas A.

    2015-01-01

    Treatment of cancer using nanoparticle-based approaches relies on the rational design of carriers with respect to size, charge, and surface properties. Polymer-based nanomaterials, inorganic materials such as gold, iron oxide, and silica as well as carbon based materials such as carbon nanotubes and graphene are being explored extensively for cancer therapy. The challenges associated with the delivery of these nanoparticles depend greatly on the type of cancer and stage of development. This review highlights design considerations to develop nanoparticle-based approaches for overcoming physiological hurdles in cancer treatment, as well as emerging research in engineering advanced delivery systems for the treatment of primary, metastatic, and multidrug resistant cancers. A growing understanding of cancer biology will continue to foster development of intelligent nanoparticle-based therapeutics that take into account diverse physiological contexts of changing disease states to improve treatment outcomes. PMID:25621200

  18. Carrier-Based Drug Delivery System for Treatment of Acne

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

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

  19. Drug Delivery Implants in the Treatment of Vitreous Inflammation

    PubMed Central

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

    2013-01-01

    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. PMID:24191132

  20. Delivery systems for the treatment of degenerated intervertebral discs.

    PubMed

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

    2015-04-01

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

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

    PubMed Central

    Debinski, Waldemar; Tatter, Stephen B

    2013-01-01

    The brain is highly accessible for nutrients and oxygen, however delivery of drugs to malignant brain tumors is a very challenging task. Convection-enhanced delivery (CED) has been designed to overcome some of the difficulties so that pharmacological agents that would not normally cross the BBB can be used for treatment. Drugs are delivered through one to several catheters placed stereotactically directly within the tumor mass or around the tumor or the resection cavity. Several classes of drugs are amenable to this technology including standard chemotherapeutics or novel experimental targeted drugs. The first Phase III trial for CED-delivered, molecularly targeted cytotoxin in the treatment of recurrent glioblastoma multiforme has been accomplished and demonstrated objective clinical efficacy. The lessons learned from more than a decade of attempts at exploiting CED for brain cancer treatment weigh critically for its future clinical applications. The main issues center around the type of catheters used, number of catheters and their exact placement; pharmacological formulation of drugs, prescreening patients undergoing treatment and monitoring the distribution of drugs in tumors and the tumor-infiltrated brain. It is expected that optimizing CED will make this technology a permanent addition to clinical management of brain malignancies. PMID:19831841

  2. Logic Regression for Provider Effects on Kidney Cancer Treatment Delivery

    PubMed Central

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

    2014-01-01

    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. PMID:24795774

  3. Sustained Release Intraocular Drug Delivery Devices for Treatment of Uveitis

    PubMed Central

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

    2011-01-01

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

  4. [Drug delivery strategies for targeted treatment of inflammatory bowel disease].

    PubMed

    Lautenschläger, C; Schmidt, C; Lange, K; Stallmach, A

    2015-03-01

    Inflammatory bowel disease (IBD) is a frequently occurring disease in young people, which is characterized by chronic inflammation of the gastrointestinal tract. The therapy of IBD is dominated by the administration of anti-inflammatory and immunosuppressive agents, which suppress the intestinal inflammatory burden and improve the disease-related symptoms. Present treatment strategies are characterized by a limited therapeutical efficacy and the occurrence of adverse drug reactions. The development of novel disease-targeted drug delivery strategies is preferable for a more effective therapy and thus demonstrates the potential to address unmet medical needs. This review gives an overview about drug delivery strategies for the treatment of IBD. Therefore, established intestine-targeting strategies for a selective drug release into the diseased part of the gastrointestinal tract will be presented, including prodrugs, and dosage forms with pH-/time-dependent drug release. Furthermore future-oriented disease-targeting strategies for a selective drug release into the intestinal inflammation will be described, including micro-/nanosized synthetic and biologic drug carriers. This novel therapeutic approach may enable a more effective anti-inflammatory treatment of IBD with reduced risks of adverse reactions. PMID:25723326

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

    SciTech Connect

    Wong, Sharon; Back, Michael; Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun; Lu, Jaide Jay

    2012-07-01

    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.

  6. IMRT dose delivery effects in radiotherapy treatment planning using Monte Carlo methods

    NASA Astrophysics Data System (ADS)

    Tyagi, Neelam

    Inter- and intra-leaf transmission and head scatter can play significant roles in Intensity Modulated Radiation Therapy (IMRT)-based treatment deliveries. In order to accurately calculate the dose in the IMRT planning process, it is therefore important that the detailed geometry of the multi-leaf collimator (MLC), in addition to other components in the accelerator treatment head be accurately modeled. In this thesis Monte Carlo (MC) methods have been used to model the treatment head of a Varian linear accelerator. A comprehensive model of the Varian 120-leaf MLC has been developed within the DPM MC code and has been verified against measurements in homogeneous and heterogeneous phantom geometries under different IMRT delivery circumstances. Accuracy of the MLC model in simulating details in the leaf geometry has been established over a range of arbitrarily shaped fields and IMRT fields. A sensitivity analysis of the effect of the electron-on-target parameters and the structure of the flattening filter on the accuracy of calculated dose distributions has been conducted. Adjustment of the electron-on-target parameters resulting in optimal agreement with measurements was an iterative process, with the final parameters representing a tradeoff between small (3x3 cm2) and large (40x40 cm2) field sizes. A novel method based on adaptive kernel density estimation, in the phase space simulation process is also presented as an alternative to particle recycling. Using this model dosimetric differences between MLC-based static (SMLC) and dynamic (DMLC) deliveries have been investigated. Differences between SMLC and DMLC, possibly related to fluence and/or spectral changes, appear to vary systematically with the density of the medium. The effect of fluence modulation due to leaf sequencing shows differences, up to 10% between plans developed with 1% and 10% fluence intervals for both SMLC and DMLC-delivered sequences. Dose differences between planned and delivered leaf sequences

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

    SciTech Connect

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

    2013-09-15

    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.

  8. Management of Cesarean Deliveries and Cesarean Scars With Osteopathic Manipulative Treatment: A Brief Report.

    PubMed

    Martingano, Daniel

    2016-07-01

    Cesarean scars pose a unique set of risks for women who have had previous cesarean deliveries. Between 1996 and 2007, the rate of trial of labor after previous cesarean delivery increased, along with reported rates of uterine rupture and other complications. Consequently, trial of labor after previous cesarean delivery and resultant vaginal birth after cesarean delivery have decreased and cesarean delivery has increased. With nearly one-third of women having cesarean delivery, the rate of rare complications such as cesarean scar ectopic pregnancy has also increased. An integration of osteopathic manipulative treatment techniques into the management of cesarean deliveries and cesarean scars has yet to be defined. The author presents 4 cases of cesarean delivery in which osteopathic manipulative treatment was integrated with successful outcomes. PMID:27367961

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

    SciTech Connect

    Nelson, Christopher; Starkschall, George; Balter, Peter; Fitzpatrick, Mathew J.; Antolak, John A.; Tolani, Naresh; Prado, Karl

    2005-01-01

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

  10. Fast and accurate sensitivity analysis of IMPT treatment plans using Polynomial Chaos Expansion.

    PubMed

    Perkó, Zoltán; van der Voort, Sebastian R; van de Water, Steven; Hartman, Charlotte M H; Hoogeman, Mischa; Lathouwers, Danny

    2016-06-21

    The highly conformal planned dose distribution achievable in intensity modulated proton therapy (IMPT) can severely be compromised by uncertainties in patient setup and proton range. While several robust optimization approaches have been presented to address this issue, appropriate methods to accurately estimate the robustness of treatment plans are still lacking. To fill this gap we present Polynomial Chaos Expansion (PCE) techniques which are easily applicable and create a meta-model of the dose engine by approximating the dose in every voxel with multidimensional polynomials. This Polynomial Chaos (PC) model can be built in an automated fashion relatively cheaply and subsequently it can be used to perform comprehensive robustness analysis. We adapted PC to provide among others the expected dose, the dose variance, accurate probability distribution of dose-volume histogram (DVH) metrics (e.g. minimum tumor or maximum organ dose), exact bandwidths of DVHs, and to separate the effects of random and systematic errors. We present the outcome of our verification experiments based on 6 head-and-neck (HN) patients, and exemplify the usefulness of PCE by comparing a robust and a non-robust treatment plan for a selected HN case. The results suggest that PCE is highly valuable for both research and clinical applications. PMID:27227661

  11. Fast and accurate sensitivity analysis of IMPT treatment plans using Polynomial Chaos Expansion

    NASA Astrophysics Data System (ADS)

    Perkó, Zoltán; van der Voort, Sebastian R.; van de Water, Steven; Hartman, Charlotte M. H.; Hoogeman, Mischa; Lathouwers, Danny

    2016-06-01

    The highly conformal planned dose distribution achievable in intensity modulated proton therapy (IMPT) can severely be compromised by uncertainties in patient setup and proton range. While several robust optimization approaches have been presented to address this issue, appropriate methods to accurately estimate the robustness of treatment plans are still lacking. To fill this gap we present Polynomial Chaos Expansion (PCE) techniques which are easily applicable and create a meta-model of the dose engine by approximating the dose in every voxel with multidimensional polynomials. This Polynomial Chaos (PC) model can be built in an automated fashion relatively cheaply and subsequently it can be used to perform comprehensive robustness analysis. We adapted PC to provide among others the expected dose, the dose variance, accurate probability distribution of dose-volume histogram (DVH) metrics (e.g. minimum tumor or maximum organ dose), exact bandwidths of DVHs, and to separate the effects of random and systematic errors. We present the outcome of our verification experiments based on 6 head-and-neck (HN) patients, and exemplify the usefulness of PCE by comparing a robust and a non-robust treatment plan for a selected HN case. The results suggest that PCE is highly valuable for both research and clinical applications.

  12. Radiation dose delivery verification in the treatment of carcinoma-cervix

    SciTech Connect

    Shrotriya, D. Srivastava, R. N. L.; Kumar, S.

    2015-06-24

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  13. Polymeric drug delivery for the treatment of glioblastoma

    PubMed Central

    Wait, Scott D.; Prabhu, Roshan S.; Burri, Stuart H.; Atkins, Tyler G.; Asher, Anthony L.

    2015-01-01

    Glioblastoma (GBM) remains an almost universally fatal diagnosis. The current therapeutic mainstay consists of maximal safe surgical resection followed by radiation therapy (RT) with concomitant temozolomide (TMZ), followed by monthly TMZ (the “Stupp regimen”). Several chemotherapeutic agents have been shown to have modest efficacy in the treatment of high-grade glioma (HGG), but blood-brain barrier impermeability remains a major delivery obstacle. Polymeric drug-delivery systems, developed to allow controlled local release of biologically active substances for a variety of conditions, can achieve high local concentrations of active agents while limiting systemic toxicities. Polymerically delivered carmustine (BCNU) wafers, placed on the surface of the tumor-resection cavity, can potentially provide immediate chemotherapy to residual tumor cells during the standard delay between surgery and chemoradiotherapy. BCNU wafer implantation as monochemotherapy (with RT) in newly diagnosed HGG has been investigated in 2 phase III studies that reported significant increases in median overall survival. A number of studies have investigated the tumoricidal synergies of combination chemotherapy with BCNU wafers in newly diagnosed or recurrent HGG, and a primary research focus has been the integration of BCNU wafers into multimodality therapy with the standard Stupp regimen. Overall, the results of these studies have been encouraging in terms of safety and efficacy. However, the data must be qualified by the nature of the studies conducted. Currently, there are no phase III studies of BCNU wafers with the standard Stupp regimen. We review the rationale, biochemistry, pharmacokinetics, and research history (including toxicity profile) of this modality. PMID:25746091

  14. Dosimetric Effects of Setup Uncertainties on Breast Treatment Delivery

    SciTech Connect

    Harron, Elizabeth Christine McCallum, Hazel Mhairi; Lambert, Elizabeth Lyn; Lee, Daniela; Lambert, Geoffrey David

    2008-01-01

    This study aimed to assess the dosimetric impact of setup errors during the delivery of radiotherapy to the breast, and use this information to make recommendations on intervention tolerances for portal imaging of breast treatments. Translational and rotational setup errors were simulated for 10 recent breast patients using an Oncentra MasterPlan treatment planning system. The effect of these errors on the breast and tumor bed target volumes receiving 95% and 107% of the prescribed dose were assessed. For the majority of patients, shifts of up to 10 mm or a 4 deg. patient rotation about the cranio-caudal axis had no significant effect on the dose distribution. Changes in dosimetry were more likely if the reference plan contained large hot or cold spots. For a typical patient, it is estimated that a shift of 5 mm in any one direction, or a 2 deg. patient rotation would not cause more than a 5% change in the target volume receiving between 95% and 107% of the prescribed dose. If combinations of errors occur, greater dosimetric changes would be expected. It is concluded that individual patient shifts of up to 5 mm or rotations about the cranio-caudal axis of 2 deg. or less are unlikely to affect dose-volume histogram parameters by an amount judged as clinically significant. Setup errors exceeding these values may cause large dosimetric changes for some patients, particularly those with larger hot or cold regions in the dose distribution, and intervention is therefore recommended.

  15. Indocyanine green delivery systems for tumour detection and treatments.

    PubMed

    Porcu, Elena P; Salis, Andrea; Gavini, Elisabetta; Rassu, Giovanna; Maestri, Marcello; Giunchedi, Paolo

    2016-01-01

    Indocyanine green (ICG) is a cyanine compound that displays fluorescent properties in the near infrared region. This dye is employed for numerous indications but nowadays its major application field regards tumour diagnosis and treatments. Optical imaging by near infrared fluorescence provides news opportunities for oncologic surgery. The imaging of ICG can be useful for intraoperative identification of several solid tumours and metastases, and sentinel lymph node detection. In addition, ICG can be used as an agent for the destruction of malignant tissue, by virtue of the production of reactive oxygen species and/or induction of a hyperthermia effect under irradiation. Nevertheless, ICG shows several drawbacks, which limit its clinical application. Several formulative strategies have been studied to overcome these problems. The rationale of the development of ICG containing drug delivery systems is to enhance the in vivo stability and biodistribution profile of this dye, allowing tumour accumulation and resulting in better efficacy. In this review, ICG containing nano-sized carriers are classified based on their chemical composition and structure. In addition to nanosystems, different formulations including hydrogel, microsystems and others loaded with ICG will be illustrated. In particular, this report describes the preparation, in vitro characterization and in vivo application of ICG platforms for cancer imaging and treatment. The promising results of all systems confirm their clinical utility but further studies are required prior to evaluating the formulations in human trials. PMID:27090752

  16. Accurate and general treatment of electrostatic interaction in Hamiltonian adaptive resolution simulations

    NASA Astrophysics Data System (ADS)

    Heidari, M.; Cortes-Huerto, R.; Donadio, D.; Potestio, R.

    2016-07-01

    In adaptive resolution simulations the same system is concurrently modeled with different resolution in different subdomains of the simulation box, thereby enabling an accurate description in a small but relevant region, while the rest is treated with a computationally parsimonious model. In this framework, electrostatic interaction, whose accurate treatment is a crucial aspect in the realistic modeling of soft matter and biological systems, represents a particularly acute problem due to the intrinsic long-range nature of Coulomb potential. In the present work we propose and validate the usage of a short-range modification of Coulomb potential, the Damped shifted force (DSF) model, in the context of the Hamiltonian adaptive resolution simulation (H-AdResS) scheme. This approach, which is here validated on bulk water, ensures a reliable reproduction of the structural and dynamical properties of the liquid, and enables a seamless embedding in the H-AdResS framework. The resulting dual-resolution setup is implemented in the LAMMPS simulation package, and its customized version employed in the present work is made publicly available.

  17. Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea

    PubMed Central

    Kim, Kyoung-Mee; Sohn, Taesung; Choi, Dongil; Kang, Hye Jin; Ryu, Min-Hee; Kim, Woo Ho; Yang, Han-Kwang

    2010-01-01

    Despite the rarity in incidence and prevalence, gastrointestinal stromal tumor (GIST) has emerged as a distinct pathogenetic entity. And the clinical management of GIST has been evolving very rapidly due to the recent recognition of its oncogenic signal transduction pathway and the introduction of new molecular-targeted therapy. Successful management of GIST requires a multidisciplinary approach firmly based on accurate histopathologic diagnosis. However, there was no standardized guideline for the management of Korean GIST patients. In 2007, the Korean GIST study group (KGSG) published the first guideline for optimal diagnosis and treatment of GIST in Korea. As the second version of the guideline, we herein have updated recent clinical recommendations and reflected changes in diagnosis, surgical and medical treatments for more optimal clinical practice for GIST in Korea. We hope the guideline can be of help in enhancing the quality of diagnosis by members of the Korean associate of physicians involving in GIST patients's care and subsequently in achieving optimal efficacy of treatment. PMID:21060741

  18. [Preterm delivery: detection of risks and preventive treatment].

    PubMed

    Althabe, F; Carroli, G; Lede, R; Belizán, J M; Althabe, O H

    1999-06-01

    Every year around the world some 13 million premature children are born. Most of these children are born in developing countries, and they account for the largest share of perinatal morbidity and mortality. This review study analyzed scientifically validated data on interventions to prevent at least some portion of these preterm deliveries and to lessen their impact on neonatal health. The Cochrane and MEDLINE bibliographic databases were consulted. Fifty review pieces and research articles were studied, relating to the following aspects of preterm delivery: risk factors and early detection of the risk of preterm delivery; preventing the risk of preterm delivery; treating preterm delivery once it has begun; and preventing neonatal respiratory distress syndrome. There were few successful approaches to the prediction, prevention, or early detection of the threat of preterm delivery. The only measures that can be recommended for all pregnant women are screening for and treating asymptomatic bacteriuria as a part of prenatal check-ups. Screening for bacterial vaginosis and treating it reduce the incidence of preterm births in pregnant women with a history of premature delivery. In addition, prophylactic cerclage decreases the incidence of premature births in pregnant women who have had more than three preterm births. To treat a delivery that starts early, with or without premature membrane rupture, the interventions that have proved to be effective are administering betamimetics to the parturient woman in order to delay delivery for 48 hours, and using indomethacin for the same purpose, as the second-choice drug. The prenatal administration of corticosteroids to the pregnant woman can induce lung maturation in the fetus and reduce respiratory distress syndrome and ventricular hemorrhage, thus decreasing neonatal mortality. There is a need to continue and support basic and epidemiological research in order to develop new knowledge on the causes and mechanisms of preterm

  19. Passive flow regulators for drug delivery and hydrocephalus treatment

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  20. Asthma control cost-utility randomized trial evaluation (ACCURATE): the goals of asthma treatment

    PubMed Central

    2011-01-01

    Background Despite the availability of effective therapies, asthma remains a source of significant morbidity and use of health care resources. The central research question of the ACCURATE trial is whether maximal doses of (combination) therapy should be used for long periods in an attempt to achieve complete control of all features of asthma. An additional question is whether patients and society value the potential incremental benefit, if any, sufficiently to concur with such a treatment approach. We assessed patient preferences and cost-effectiveness of three treatment strategies aimed at achieving different levels of clinical control: 1. sufficiently controlled asthma 2. strictly controlled asthma 3. strictly controlled asthma based on exhaled nitric oxide as an additional disease marker Design 720 Patients with mild to moderate persistent asthma from general practices with a practice nurse, age 18-50 yr, daily treatment with inhaled corticosteroids (more then 3 months usage of inhaled corticosteroids in the previous year), will be identified via patient registries of general practices in the Leiden, Nijmegen, and Amsterdam areas in The Netherlands. The design is a 12-month cluster-randomised parallel trial with 40 general practices in each of the three arms. The patients will visit the general practice at baseline, 3, 6, 9, and 12 months. At each planned and unplanned visit to the general practice treatment will be adjusted with support of an internet-based asthma monitoring system supervised by a central coordinating specialist nurse. Patient preferences and utilities will be assessed by questionnaire and interview. Data on asthma control, treatment step, adherence to treatment, utilities and costs will be obtained every 3 months and at each unplanned visit. Differences in societal costs (medication, other (health) care and productivity) will be compared to differences in the number of limited activity days and in quality adjusted life years (Dutch EQ5D, SF6D

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

    NASA Astrophysics Data System (ADS)

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

    2012-05-01

    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.

  2. Health literacy in HIV treatment: accurate understanding of key biological treatment principles is not required for good ART adherence.

    PubMed

    Laws, M Barton; Danielewicz, Michael; Rana, Aadia; Kogelman, Laura; Wilson, Ira B

    2015-04-01

    Findings on the relationship between health literacy and outcomes in HIV have been inconsistent. Health literacy has previously been operationalized as general functional literacy, but has not included content knowledge about HIV disease and treatment. Semi-structured interviews with people living with HIV in 2 U.S. cities, including questions about the etiology, pathophysiology and treatment of HIV. We compared responses to biomedical conceptions. The 32 respondents were demographically diverse. Although most understood that HIV degrades the immune system, none could explain the nature of a virus, or the mechanism of antiretroviral (ARV) drug action. Fewer than half accurately reported that it is desirable to have a high CD4+ cell count and low viral load. A minority understood the concept of drug resistance. While most believed that strict adherence to ARV regimens was important to maintain health, three believed that periodic treatment interruption was beneficial, and three believed they should not take ARVs when they used alcohol or illicit drugs. Respondents generally had very limited, and often inaccurate biomedical understanding of HIV disease. Most reported good regimen adherence but did not have any mechanistic rationale for it. The failure to find a consistent relationship between health literacy and ARV adherence may be largely because most people simply follow their doctors' instructions, without the need for deep understanding. PMID:25354736

  3. Health Literacy in HIV Treatment: Accurate Understanding of Key Biological Treatment Principles is Not Required for Good ART Adherence

    PubMed Central

    Laws, M. Barton; Danielewicz, Michael; Rana, Aadia; Kogelman, Laura; Wilson, Ira B.

    2016-01-01

    Findings on the relationship between health literacy and outcomes in HIV have been inconsistent. Health literacy has previously been operationalized as general functional literacy, but has not included content knowledge about HIV disease and treatment. Semi-structured interviews with people living with HIV in 2 U.S. cities, including questions about the etiology, pathophysiology and treatment of HIV. We compared responses to biomedical conceptions. The 32 respondents were demographically diverse. Although most understood that HIV degrades the immune system, none could explain the nature of a virus, or the mechanism of antiretroviral (ARV) drug action. Fewer than half accurately reported that it is desirable to have a high CD4+ cell count and low viral load. A minority understood the concept of drug resistance. While most believed that strict adherence to ARV regimens was important to maintain health, three believed that periodic treatment interruption was beneficial, and three believed they should not take ARVs when they used alcohol or illicit drugs. Respondents generally had very limited, and often inaccurate biomedical understanding of HIV disease. Most reported good regimen adherence but did not have any mechanistic rationale for it. The failure to find a consistent relationship between health literacy and ARV adherence may be largely because most people simply follow their doctors’ instructions, without the need for deep understanding. PMID:25354736

  4. Progesterone use after successful treatment of threatened pre-term delivery.

    PubMed

    Areia, A; Fonseca, E; Moura, P

    2013-10-01

    Pre-term delivery is the leading cause of neonatal morbidity, mortality and long-term sequels. This is an open label randomised controlled trial with women with confirmed threatened pre-term labour (TPTL) after efficient tocolytic therapy with atosiban. The main outcome measure of this study was the latency period until delivery and secondary outcomes were the number of recurrent episodes of TPTL and fetal and maternal morbidity. Patients were assigned to treatment or control groups using a computer generated randomisation table. The treatment group received 200 mg vaginal progesterone daily until delivery and the control group received no therapy or placebo. The study cohort comprised 52 pregnant women, 26 in each arm, showing similar characteristics; the treatment group had a longer latency period until delivery and this was statistically significant (55 vs 38 days, p = 0.024). This study points to the benefits of the vaginal administration of progesterone, especially in prolonging latency period until delivery. PMID:24127952

  5. Bayesian statistical treatment of the fluorescence of AFLP bands leads to accurate genetic structure inference.

    PubMed

    Gaggiotti, Oscar E

    2010-11-01

    Ever since the introduction of allozymes in the 1960s, evolutionary biologists and ecologists have continued to search for more powerful molecular markers to estimate important parameters such as effective population size and migration rates and to make inferences about the demographic history of populations, the relationships between individuals and the genetic architecture of phenotypic variation (Bensch & Akesson 2005; Bonin et al. 2007). Choosing a marker requires a thorough consideration of the trade-offs associated with the different techniques and the type of data obtained from them. Some markers can be very informative but require substantial amounts of start-up time (e.g. microsatellites), while others require very little time but are much less polymorphic. Amplified fragment length polymorphism (AFLP) is a firmly established molecular marker technique that falls in this latter category. AFLPs are widely distributed throughout the genome and can be used on organisms for which there is no a priori sequence information (Meudt & Clarke 2007). These properties together with their moderate cost and short start-up time have made them the method of choice for many molecular ecology studies of wild species (Bensch & Akesson 2005). However, they have a major disadvantage, they are dominant. This represents a very important limitation because many statistical genetics methods appropriate for molecular ecology studies require the use of codominant markers. In this issue, Foll et al. (2010) present an innovative hierarchical Bayesian method that overcomes this limitation. The proposed approach represents a comprehensive statistical treatment of the fluorescence of AFLP bands and leads to accurate inferences about the genetic structure of natural populations. Besides allowing a quasi-codominant treatment of AFLPs, this new method also solves the difficult problems posed by subjectivity in the scoring of AFLP bands. PMID:20958811

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

    SciTech Connect

    Baumgartner, S.; Bieli, R.; Bergmann, U. C.

    2012-07-01

    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)

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

    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

  8. Uptake and delivery of hepatitis C treatment in opiate substitution treatment: perceptions of clients and health professionals.

    PubMed

    Treloar, C; Newland, J; Rance, J; Hopwood, M

    2010-12-01

    Uptake of treatment for hepatitis C virus (HCV) infection is very low particularly among people who have injected drugs. Opiate substitution treatment (OST) programs, with a high prevalence of people living with HCV, have been a site of growing interest in the delivery of hepatitis C treatment. There has been no exploration of OST clients' and health professionals' perceptions of the barriers and facilitators to uptake and delivery of HCV treatment in OST clinics from personal and organizational perspectives. This qualitative study involved interviews with 27 OST clients in New South Wales and a focus group and interviews with 22 Australian OST health professionals. Clients and health professionals viewed hepatitis C treatment in OST as a 'one-stop-shop' model which could increase access to and uptake of treatment and build on existing relationships of trust between OST client and health professional. Elements of the organizational culture were also noted as barriers to HCV treatment delivery including concerns about confidentiality, lack of discussion of HCV treatment and that HCV treatment was not perceived by clinicians as a legitimate activity of OST clinics. OST client participants also reported a number of personal barriers to engaging with HCV treatment including family responsibilities (and concerns about treatment side effects), unstable housing, comorbidities and perceptions of the unsatisfactory level of treatment efficacy. These findings emphasize the need for future research and delivery of services which addresses the complexity of care and treatment for people in marginalized social circumstances. PMID:20070504

  9. Women who conceived with infertility treatment were more likely to receive planned cesarean deliveries in Taiwan.

    PubMed

    Chien, Li-Yin; Lee, Yu-Hsiang; Lin, Yu-Hung; Tai, Chen-Jei

    2015-06-01

    The objective of this study was to examine the effect of conception with infertility treatment on planned cesarean delivery. The participants were from a panel of primiparous pregnant women in northern Taiwan. The data analysis included 771 women with a singleton pregnancy, of whom 160 had a planned cesarean delivery and 611 who had a vaginal delivery. The study women answered structured questionnaires during the second and third trimesters of pregnancy, and at one-month postpartum. Women who conceived with infertility treatment were more likely to have planned cesarean deliveries than women who conceived without it (44.7% versus 18.1%, p < 0.001; crude odds ratio: 3.66, 95% confidence interval [CI]: 2.24-5.98). After adjustment for maternal age over 35 years, whether they were currently unmarried, selection of time for birth in advance, gestational hypertension, and birthweight < 2500 g, women who conceived with infertility treatment were 2.95 times (95% CI: 1.47-5.92) more likely to have planned cesarean deliveries. The increased risk for planned cesarean deliveries among singleton women who conceived with infertility treatment cannot be explained by older maternal age or higher number of morbidities during pregnancy. Counseling for women who conceive with infertility treatments may be needed to decrease unnecessary cesarean deliveries. PMID:25581216

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

    PubMed

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

    2014-01-01

    Many potential drugs for the treatment of neurological diseases are unable to reach the brain in sufficient enough concentrations to be therapeutic because of the blood brain barrier. On the other hand, direct delivery of drugs to the brain provides the possibility of a greater therapeutic-toxic ratio than with systemic drug delivery. The use of intranasal delivery of therapeutic agents to the brain provides a means of bypassing the blood brain barrier in a non-invasive manner. In this respect, nanosized drug carriers were shown to enhance the delivery of drugs to CNS compared to equivalent drug solution formulations. Neurological conditions that have been studied in animal models that could benefit from nose-to-brain delivery of nanotherapeutics include pain, epilepsy, neurodegenerative disease and infectious diseases. The delivery of drugs to the brain via the nose-to-brain route holds great promise, on the basis of preclinical research by means of drug delivery systems such as polymeric nanoparticles and clinical data related to intranasal delivery to CNS of large molecular weight biologics administered in solution, but safety issues about toxicity on nasal mucosa, Np transport into the brain, delivery only to specific brain regions and variability in the adsorbed dose still represent research topics that need to be considered, with a view of clinical translation of these delivery systems. PMID:25039773

  11. Development of a geometrically accurate imaging protocol at 3 Tesla MRI for stereotactic radiosurgery treatment planning

    NASA Astrophysics Data System (ADS)

    Zhang, B.; MacFadden, D.; Damyanovich, A. Z.; Rieker, M.; Stainsby, J.; Bernstein, M.; Jaffray, D. A.; Mikulis, D.; Ménard, C.

    2010-11-01

    The purpose of this study is to develop a geometrically accurate imaging protocol at 3 T magnetic resonance imaging (MRI) for stereotactic radiosurgery (SRS) treatment planning. In order to achieve this purpose, a methodology is developed to investigate the geometric accuracy and stability of 3 T MRI for SRS in phantom and patient evaluations. Forty patients were enrolled on a prospective clinical trial. After frame placement prior to SRS, each patient underwent 3 T MRI after 1.5 T MRI and CT. MR imaging protocols included a T1-weighted gradient echo sequence and a T2-weighted spin echo sequence. Phantom imaging was performed on 3 T prior to patient imaging using the same set-up and imaging protocols. Geometric accuracy in patients and phantoms yielded comparable results for external fiducial reference deviations and internal landmarks between 3 T and 1.5 T MRI (mean <=0.6 mm; standard deviation <=0.3 mm). Mean stereotactic reference deviations between phantoms and patients correlated well (T1: R = 0.79; T2: R = 0.84). Statistical process control analysis on phantom QA data demonstrated the stability of our SRS imaging protocols, where the geometric accuracy of the 3 T SRS imaging protocol is operating within the appropriate tolerance. Our data provide evidence supporting the spatial validity of 3 T MRI for targeting SRS under imaging conditions investigated. We have developed a systematic approach to achieve confidence on the geometric integrity of a given imaging system/technique for clinical integration in SRS application.

  12. Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning.

    PubMed

    Liu, Shi; Wu, Yu; Wooten, H Omar; Green, Olga; Archer, Brent; Li, Harold; Yang, Deshan

    2016-01-01

    A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image-guided radiation therapy (MR-IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam-on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam-on time can be calculated using both the planned beam-on time and the decay-corrected dose rate. To predict the remain-ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

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

    PubMed

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

    2012-11-10

    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

  15. Using Fluorescence Imaging to Track Drug Delivery and Guide Treatment Planning In Vivo.

    PubMed

    Lin, Qiaoya; Huang, Huang; Chen, Juan; Zheng, Gang

    2016-01-01

    Imaging has become an indispensable tool in both clinical medicine and preclinical sciences. It enables doctors to locate sites of cancer/disease, track drug delivery, and guide operative planning, thus enhancing the treatment efficacy. Recently, we developed a multimodal theranostic lipid nanoparticles, named HPPS(NIR)-chol-siRNA with its built-in near-infrared (NIR) fluorescent probe core as a useful surrogate for tracking small interfering RNA (siRNA) delivery. By using the image co-registration of computed tomography (CT) and fluorescence molecular tomography (FMT), we achieved noninvasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, thus enabling efficacious RNA interference (RNAi) therapy. In this chapter, we introduce this method to illustrate the use of CT-FMT co-registration for tracking drug delivery and guiding treatment planning in vivo. PMID:27283425

  16. Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma.

    PubMed

    Byrne, James D; Jajja, Mohammad R N; Schorzman, Allison N; Keeler, Amanda W; Luft, J Christopher; Zamboni, William C; DeSimone, Joseph M; Yeh, Jen Jen

    2016-02-23

    Poor delivery and systemic toxicity of many cytotoxic agents, such as the recent promising combination chemotherapy regimen of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), restrict their full utility in the treatment of pancreatic cancer. Local delivery of chemotherapies has become possible using iontophoretic devices that are implanted directly onto pancreatic tumors. We have fabricated implantable iontophoretic devices and tested the local iontophoretic delivery of FOLFIRINOX for the treatment of pancreatic cancer in an orthotopic patient-derived xenograft model. Iontophoretic delivery of FOLFIRINOX was found to increase tumor exposure by almost an order of magnitude compared with i.v. delivery with substantially lower plasma concentrations. Mice treated for 7 wk with device FOLFIRINOX experienced significantly greater tumor growth inhibition compared with i.v. FOLFIRINOX. A marker of cell proliferation, Ki-67, was stained, showing a significant reduction in tumor cell proliferation. These data capitalize on the unique ability of an implantable iontophoretic device to deliver much higher concentrations of drug to the tumor compared with i.v. delivery. Local iontophoretic delivery of cytotoxic agents should be considered for the treatment of patients with unresectable nonmetastatic disease and for patients with the need for palliation of local symptoms, and may be considered as a neoadjuvant approach to improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer. PMID:26858448

  17. Skin laser treatments enhancing transdermal delivery of ALA.

    PubMed

    Gómez, Clara; Costela, Ángel; García-Moreno, Inmaculada; Llanes, Felipe; Teijón, José M; Blanco, M Dolores

    2011-01-01

    Drug delivery across skin has been limited due to barrier properties of the skin, especially those of the stratum corneum (SC). Use of the laser radiation has been suggested for the controlled removal of the SC. The purpose of this study was to study in vitro the influence of infrared radiation from the erbium:yttrium-aluminum-garnet (Er:YAG) laser (λ = 2940  nm), and visible from the 2nd harmonic of a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (λ = 532  nm) on transdermal delivery of 5-aminolevulinic acid (ALA). Pinna skin of the inner side of rabbit ear was used for skin permeation. The light sources were an Er:YAG laser (Key III Plus KaVo) and a Q-switched Nd:YAG laser (Lotis TII SL-2132). Permeation study, morphological and structural skin examination by histology and differential scanning calorimetry (DSC) were carried out. Permeation profiles and histological observations obtained after irradiation with infrared and visible laser radiation differed due to different biophysical effects on irradiated skin. Wavelength of 2940  nm required lower energy contribution to produce the same level of permeation than visible radiation at 532  nm. Structural analysis by DSC shows a selective impact on the lipidic structure. Laser pretreatment enhanced the delivery of ALA trough the skin by SC ablation. PMID:20589948

  18. Imaging-guided delivery of RNAi for anticancer treatment.

    PubMed

    Wang, Junqing; Mi, Peng; Lin, Gan; Wáng, Yì Xiáng J; Liu, Gang; Chen, Xiaoyuan

    2016-09-01

    The RNA interference (RNAi) technique is a new modality for cancer therapy, and several candidates are being tested clinically. In the development of RNAi-based therapeutics, imaging methods can provide a visible and quantitative way to investigate the therapeutic effect at anatomical, cellular, and molecular level; to noninvasively trace the distribution; to and study the biological processes in preclinical and clinical stages. Their abilities are important not only for therapeutic optimization and evaluation but also for shortening of the time of drug development to market. Typically, imaging-functionalized RNAi therapeutics delivery that combines nanovehicles and imaging techniques to study and improve their biodistribution and accumulation in tumor site has been progressively integrated into anticancer drug discovery and development processes. This review presents an overview of the current status of translating the RNAi cancer therapeutics in the clinic, a brief description of the biological barriers in drug delivery, and the roles of imaging in aspects of administration route, systemic circulation, and cellular barriers for the clinical translation of RNAi cancer therapeutics, and with partial content for discussing the safety concerns. Finally, we focus on imaging-guided delivery of RNAi therapeutics in preclinical development, including the basic principles of different imaging modalities, and their advantages and limitations for biological imaging. With growing number of RNAi therapeutics entering the clinic, various imaging methods will play an important role in facilitating the translation of RNAi cancer therapeutics from bench to bedside. PMID:26805788

  19. The Impact of Advanced Technologies on Treatment Deviations in Radiation Treatment Delivery

    SciTech Connect

    Marks, Lawrence B. Light, Kim L.; Hubbs, Jessica L.; Georgas, Debra L.; Jones, Ellen L.; Wright, Melanie C.; Willett, Christopher G.; Yin Fangfang

    2007-12-01

    Purpose: To assess the impact of new technologies on deviation rates in radiation therapy (RT). Methods and Materials: Treatment delivery deviations in RT were prospectively monitored during a time of technology upgrade. In January 2003, our department had three accelerators, none with 'modern' technologies (e.g., without multileaf collimators [MLC]). In 2003 to 2004, we upgraded to five new accelerators, four with MLC, and associated advanced capabilities. The deviation rates among patients treated on 'high-technology' versus 'low-technology' machines (defined as those with vs. without MLC) were compared over time using the two-tailed Fisher's exact test. Results: In 2003, there was no significant difference between the deviation rate in the 'high-technology' versus 'low-technology' groups (0.16% vs. 0.11%, p = 0.45). In 2005 to 2006, the deviation rate for the 'high-technology' groups was lower than the 'low-technology' (0.083% vs. 0.21%, p = 0.009). This difference was caused by a decline in deviations on the 'high-technology' machines over time (p = 0.053), as well as an unexpected trend toward an increase in deviations over time on the 'low-technology' machines (p = 0.15). Conclusions: Advances in RT delivery systems appear to reduce the rate of treatment deviations. Deviation rates on 'high-technology' machines with MLC decline over time, suggesting a learning curve after the introduction of new technologies. Associated with the adoption of 'high-technology' was an unexpected increase in the deviation rate with 'low-technology' approaches, which may reflect an over-reliance on tools inherent to 'high-technology' machines. With the introduction of new technologies, continued diligence is needed to ensure that staff remain proficient with 'low-technology' approaches.

  20. Extracellular Vesicles as Novel Delivery Tools for Cancer Treatment.

    PubMed

    Erkan, Erdogan Pekcan; Saydam, Okay

    2016-01-01

    Extracellular vesicles (EVs) are different types of membrane-derived vesicles that originate from the endosomal pathway or the plasma membrane. These vesicles are used as "carriers" in intercellular communication, and are responsible for the transfer of biological cargo (lipids, proteins, RNA species, and DNA) between different cells. Despite the shortcomings in our knowledge of EV biology, attempts to employ EVs as natural delivery tools for therapeutic purposes have been partly successful in different settings. In this review, we highlight this unique potential of EVs, and discuss previous examples and future scenarios. PMID:26412464

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

    PubMed

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

    2013-01-01

    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

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

    PubMed Central

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

    2013-01-01

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

  3. Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases.

    PubMed

    Meredith, M Elizabeth; Salameh, Therese S; Banks, William A

    2015-07-01

    The blood-brain barrier (BBB) is a major impediment to the therapeutic delivery of peptides and proteins to the brain. Intranasal delivery often provides a non-invasive means to bypass the BBB. Advantages of using intranasal delivery include minimizing exposure to peripheral organs and tissues, thus reducing systemic side effects. It also allows substances that typically have rapid degradation in the blood time to exert their effect. Intranasal delivery provides the ability to target proteins and peptides to specific regions of the brain when administered with substrates like cyclodextrins. In this review, we examined the use of intranasal delivery of various proteins and peptides that have implications in the treatment of neurodegenerative diseases, focusing especially on albumin, exendin/GLP-1, GALP, insulin, leptin, and PACAP. We have described their rationale for use, distribution in the brain after intranasal injection, how intranasal administration differed from other modes of delivery, and their use in clinical trials, if applicable. Intranasal delivery of drugs, peptides, and other proteins could be very useful in the future for the prevention or treatment of brain related diseases. PMID:25801717

  4. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

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

  5. Treatment planning for SBRT using automated field delivery: A case study

    SciTech Connect

    Ritter, Timothy A.; Owen, Dawn; Brooks, Cassandra M.; Stenmark, Matthew H.

    2015-04-01

    Stereotactic body radiation therapy (SBRT) treatment planning and delivery can be accomplished using a variety of techniques that achieve highly conformal dose distributions. Herein, we describe a template-based automated treatment field approach that enables rapid delivery of more than 20 coplanar fields. A case study is presented to demonstrate how modest adaptations to traditional SBRT planning can be implemented to take clinical advantage of this technology. Treatment was planned for a left-sided lung lesion adjacent to the chest wall using 25 coplanar treatment fields spaced at 11° intervals. The plan spares the contralateral lung and is in compliance with the conformality standards set forth in Radiation Therapy and Oncology Group protocol 0915, and the dose tolerances found in the report of the American Association of Physicists in Medicine Task Group 101. Using a standard template, treatment planning was accomplished in less than 20 minutes, and each 10 Gy fraction was delivered in approximately 5.4 minutes. For those centers equipped with linear accelerators capable of automated treatment field delivery, the use of more than 20 coplanar fields is a viable SBRT planning approach and yields excellent conformality and quality combined with rapid planning and treatment delivery. Although the case study discusses a laterally located lung lesion, this technique can be applied to centrally located tumors with similar results.

  6. A software tool to automatically assure and report daily treatment deliveries by a Cobalt-60 radiation therapy device.

    PubMed

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

    2016-01-01

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

  7. Depression and diabetes: treatment and health-care delivery.

    PubMed

    Petrak, Frank; Baumeister, Harald; Skinner, Timothy C; Brown, Alex; Holt, Richard I G

    2015-06-01

    Despite research efforts in the past 20 years, scientific evidence about screening and treatment for depression in diabetes remains incomplete and is mostly focused on North American and European health-care systems. Validated instruments to detect depression in diabetes, although widely available, only become effective and thus recommended if subsequent treatment pathways are accessible, which is often not the case. Because of the well known adverse effects of the interaction between depression and diabetes, treatment goals should focus on the remission or improvement of depression as well as improvement in glycaemic control as a marker for subsequent diabetes outcome. Scientific evidence evaluating treatment for depression in type 1 and type 2 diabetes shows that depression can be treated with moderate success by various psychological and pharmacological interventions, which are often implemented through collaborative care and stepped-care approaches. The evidence for improved glycaemic control in the treatment of depression by use of selective serotonin reuptake inhibitors or psychological approaches is conflicting; only some analyses show small to moderate improvements in glycaemic control. More research is needed to evaluate treatment of different depression subtypes in people with diabetes, the cost-effectiveness of treatments, the use of health-care resources, the need to account for cultural differences and different health-care systems, and new treatment and prevention approaches. PMID:25995125

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

    SciTech Connect

    Suzuki, Kazumichi; Gillin, Michael T.; Sahoo, Narayan; Zhu, X. Ronald; Lee, Andrew K.; Lippy, Denise

    2011-07-15

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

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

    PubMed Central

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

    2015-01-01

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

  10. Nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

    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

  12. Poster — Thur Eve — 33: The Influence of a Modeled Treatment Couch on Dose Distributions During IMRT and RapidArc Treatment Delivery

    SciTech Connect

    Aldosary, Ghada; Nobah, Ahmad; Al-Zorkani, Faisal; Moftah, Belal; Devic, Slobodan

    2014-08-15

    Treatment couches have been known to perturb dose delivery in patients. This effect is most pronounced in techniques such as IMRT and RapidArc. Although modern treatment planning systems (TPS) include data for a “default” treatment couch, actual couches are not manufactured identically. Thus, variations in their Hounsfield Unit (HU) values may exist. This study demonstrates a practical and simple method of acquiring reliable HU data for any treatment couch. We also investigate the effects of both the default and modeled treatment couches on absorbed dose. Experimental verifications show that by neglecting to incorporate the treatment couch in the TPS, dose differences of up to 9.5% and 7.3% were present for 4 MV and 10 MV photon beams, respectively. Furthermore, a clinical study based on a cohort of 20 RapidArc and IMRT (brain, pelvis and abdominal) cases is performed. 2D dose distributions show that without the couch in the planning phase, differences ≤ 4.6% and 5.9% for RapidArc and IMRT cases are present for the same cases that the default couch was added to. Additionally, in comparison to the default couch, employing the modeled couch in the calculation process influences dose distributions by ≤ 2.7% and 8% for RapidArc and IMRT cases, respectively. This result was found to be site specific; where an accurate couch proves to be preferable for IMRT brain plans. As such, adding the couch during dose calculation decreases dose calculation errors, and a precisely modeled treatment couch offers higher dose delivery accuracy for brain treatment using IMRT.

  13. Effects of flattening filter-free and volumetric-modulated arc therapy delivery on treatment efficiency.

    PubMed

    Thomas, Evan M; Popple, Richard A; Prendergast, Brendan M; Clark, Grant M; Dobelbower, Michael C; Fiveash, John B

    2013-01-01

    Flattening filter-free (FFF) beams are available on an increasing number of commercial linear accelerators. FFF beams have higher dose rates than flattened beams of equivalent energy which can lead to increased efficiency of treatment delivery, especially in conjunction with increased FFF beam energy and arc-based delivery configurations. The purpose of this study is to quantify and assess the implications of improved treatment efficiency for several FFF delivery options on common types of linac applicable radiotherapy. Eleven characteristic cases representative of a variety of clinical treatment sites and prescription doses were selected from our patient population. Treatment plans were generated for a Varian TrueBeam linear accelerator. For each case, a reference plan was created using DMLC IMRT with 6MV flat beams. From the same initial objectives, plans were generated using DMLC IMRT and volumetric-modulated arc therapy (VMAT) with 6 MV FFF and 10 MV FFF beams (max. dose rates of 1400 and 2400 MU/min, respectively). The plans were delivered to a phantom; beam-on time, total treatment delivery time, monitor units (MUs), and integral dose were recorded. For plans with low dose fractionations (1.8-2.0 & 3.85 Gy/fraction), mean beam-on time difference between reference plan and most efficient FFF plan was 0.56 min (41.09% decrease); mean treatment delivery time difference between the reference plan and most efficient FFF plan was 1.54 min (range: 0.31-3.56 min), a relative improvement of 46.1% (range: 29.2%-59.2%). For plans with high dose fractionations (16-20 Gy/fraction), mean beam-on time difference was 6.79 min (74.9% decrease); mean treatment delivery time difference was 8.99 min (range: 5.40-13.05 min), a relative improvement of 71.1% (range: 53.4%- 82.4%). 10 MV FFF VMAT beams generated the most efficient plan, except in the spine SBRT case. The distribution of monitor unit counts did not vary by plan type. In cases where respiratory motion management would

  14. Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment

    PubMed Central

    Ellis, Jason A.; Banu, Matei; Hossain, Shaolie S.; Singh-Moon, Rajinder; Lavine, Sean D.; Bruce, Jeffrey N.; Joshi, Shailendra

    2015-01-01

    Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed. PMID:26819758

  15. Application of combined rigid choledochoscope and accurate positioning method in the adjuvant treatment of bile duct stones

    PubMed Central

    Wang, Ping; Chen, Xiaowu; Sun, Beiwang; Liu, Yanmin

    2015-01-01

    To explore the clinical effect of percutaneous transhepatic cholangioscopic lithotomy (PTCSL) combined with rigid choledochoscope and accurate positioning in the treatment of calculus of bile duct. This study retrospectively reviewed 162 patients with hepatolithiasis at the First Affiliated Hospital of Guangzhou Medical University between 2001 and 2013 were assigned to hard lens group or traditional PTCSL group. Compared with the traditional PTCSL, PTCSL with rigid choledochoscope can shorten the interval time which limit the PTCSL application. The operation time (45 vs 78, P=0.003), the number of operation (1.62 vs 1.97, P=0.031), and blood loss (37.8 vs 55.1, P=0.022) were better in hard lens group while the stone residual and complication had no significant differences. Rigid choledochoscope is a safe, minimally invasive and effective method in the treatment of bile duct stones. Accurate positioning method can effectively shorten operation process time. PMID:26629183

  16. [Cognitive-behavioural therapy for sexual dysfunctions: treatment, etiology and accurate diagnosing of premature ejaculation].

    PubMed

    Rawińska, Marta; Fijałkowska, Sylwia

    2014-01-01

    Premature ejaculation (PE) is one of the most common male sexual dysfunctions. Successful treatment of PE has been hampered by the existence of a variety of definitions and diagnostic criteria and the lack of large, long-term studies of treatment efficacy. Numerous, diverse treatment approaches with varying degrees of efficacy have been used; these include behavioral, cognitive, and sex therapy techniques, and pharmacologic management with antidepressants, phosphodiesterase-5 inhibitors, and topical anesthetics. Combining a specific pharmacologic treatment for premature ejaculation with appropriate cognitive, behavioral, and sex therapy techniques should improve the overall understanding and management of sexual dysfunction, resulting in a sustainable increase in sexual satisfaction and decrease in distress for man. The aim of this article is to raise awareness of the prevalence of PE, its symptoms, and the impact it has on both partners and to discuss the benefits of adding limited behavioral and cognitive sex therapy techniques to drug therapy. PMID:24645584

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

    SciTech Connect

    Zhang Tiezhi . E-mail: tiezhi.zhang@beaumont.edu; Lu Weiguo; Olivera, Gustavo H.; Keller, Harry; Jeraj, Robert; Manon, Rafael; Mehta, Minesh; Mackie, Thomas R.; Paliwal, Bhudatt

    2007-08-01

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

  18. Deep soil mixing for reagent delivery and contaminant treatment

    SciTech Connect

    Korte, N.; Gardner, F.G.; Cline, S.R.; West, O.R.

    1997-12-31

    Deep soil mixing was evaluated for treating clay soils contaminated with TCE and its byproducts at the Department of Energy`s Kansas City Plant. The objective of the project was to evaluate the extent of limitations posed by the stiff, silty-clay soil. Three treatment approaches were tested. The first was vapor stripping. In contrast to previous work, however, laboratory treatability studies indicated that mixing saturated, clay soil was not efficient unless powdered lime was added. Thus, powder injection of lime was attempted in conjunction with the mixing/stripping operation. In separate treatment cells, potassium permanganate solution was mixed with the soil as a means of destroying contaminants in situ. Finally, microbial treatment was studied in a third treatment zone. The clay soil caused operational problems such as breakage of the shroud seal and frequent reagent blowouts. Nevertheless, treatment efficiencies of more than 70% were achieved in the saturated zone with chemical oxidation. Although expensive ($1128/yd{sup 3}), there are few alternatives for soils of this type.

  19. Quality control procedures for dynamic treatment delivery techniques involving couch motion

    SciTech Connect

    Yu, Victoria Y.; Fahimian, Benjamin P.; Xing, Lei; Hristov, Dimitre H.

    2014-08-15

    In this study, the authors introduce and demonstrate quality control procedures for evaluating the geometric and dosimetric fidelity of dynamic treatment delivery techniques involving treatment couch motion synchronous with gantry and multileaf collimator (MLC). Tests were designed to evaluate positional accuracy, velocity constancy and accuracy for dynamic couch motion under a realistic weight load. A test evaluating the geometric accuracy of the system in delivering treatments over complex dynamic trajectories was also devised. Custom XML scripts that control the Varian TrueBeam™ STx (Serial #3) axes in Developer Mode were written to implement the delivery sequences for the tests. Delivered dose patterns were captured with radiographic film or the electronic portal imaging device. The couch translational accuracy in dynamic treatment mode was 0.01 cm. Rotational accuracy was within 0.3°, with 0.04 cm displacement of the rotational axis. Dose intensity profiles capturing the velocity constancy and accuracy for translations and rotation exhibited standard deviation and maximum deviations below 3%. For complex delivery involving MLC and couch motions, the overall translational accuracy for reproducing programmed patterns was within 0.06 cm. The authors conclude that in Developer Mode, TrueBeam™ is capable of delivering dynamic treatment delivery techniques involving couch motion with good geometric and dosimetric fidelity.

  20. Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma

    PubMed Central

    Arshad, Azeem; Yang, Bin; Bienemann, Alison S.; Barua, Neil U.; Wyatt, Marcella J.; Woolley, Max; Johnson, Dave E.; Edler, Karen J.; Gill, Steven S.

    2015-01-01

    We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas. PMID:26186224

  1. Skin delivery of kojic acid-loaded nanotechnology-based drug delivery systems for the treatment of skin aging.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Uskoković, Vuk

    2015-01-01

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

  4. Maimonides: an early but accurate view on the treatment of haemorrhoids

    PubMed Central

    Magrill, Dan; Sekaran, Prabhu

    2007-01-01

    Moses Maimonides was not only one of the most influential religious figures of the middle ages, but also a pioneer in a wide variety of medical practices. A brief history of his life, and what is known about his medical education, is given here. His paper on haemorrhoids is summarised, as well as a review of the current understanding of the pathogenesis, prevention and treatment of this common condition. The comparison of Maimonides' writings to modern understanding of not only the prevention and treatment of haemorrhoids, but also his approach to the patient as a whole in terms of pre‐ and postoperative care, demonstrate how ahead of his time this great philosopher was. PMID:17488868

  5. Tunable Lipidoid-Telodendrimer Hybrid Nanoparticles for Intracellular Protein Delivery in Brain Tumor Treatment.

    PubMed

    Wang, Xu; Bodman, Alexa; Shi, Changying; Guo, Dandan; Wang, Lili; Luo, Juntao; Hall, Walter A

    2016-08-01

    A strategy to precisely engineer lipidoid-telodendrimer binary hybrid nanoparticles that offer enhanced cell membrane permeability for therapeutic proteins to reach the intracellular targets is established. The highly controllable biochemical and physical properties of the nanoparticles make them promising for protein-based brain cancer treatment with the assistance of convection-enhanced delivery. PMID:27375237

  6. Levodopa delivery systems for the treatment of Parkinson's disease: an overview.

    PubMed

    Goole, J; Amighi, K

    2009-10-01

    This review describes the different drug delivery systems containing levodopa that are used in the treatment of Parkinson's disease. Their composition, process of preparation, advantages, disadvantages and limitations are discussed as well as the major objective in the management of Parkinson's disease according to the pathology of the disease. PMID:19651197

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

    PubMed

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

    2013-05-01

    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

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

    PubMed Central

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

    2013-01-01

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

  9. Mitochondria-targeted drug delivery system for cancer treatment.

    PubMed

    Chen, Zhi-Peng; Li, Man; Zhang, Liu-Jie; He, Jia-Yu; Wu, Li; Xiao, Yan-Yu; Duan, Jin-Ao; Cai, Ting; Li, Wei-Dong

    2016-07-01

    Mitochondria are one type of the major organelles in the cell, participating in a variety of important physiological and biochemical processes, such as tricarboxylic acid cycle, fatty acid metabolism and oxidative phosphorylation. Meanwhile, it also happens to be the key regulator of apoptosis by triggering the complex cell-death processes through a variety of mechanisms. Since it plays a pivotal role in cell-death, a mitochondria-targeted treatment strategy could be promising for cancer therapy. In this comprehensive review, we focused on the mechanisms of mitochondrial targeting and a variety of strategies to realize the purpose of mitochondrial targeting, including that based on the use of lipophilic cations, and mitochondrial targeting signal peptides (MTS) as well as cell-penetrating peptides (CPPs). Then on this basis we present some several developed strategies for multifunctional mitochondria-targeted agents so as to achieve the good anti-cancer therapeutic effects. PMID:26548930

  10. Improved delivery of magnetic nanoparticles with chemotherapy cancer treatment

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  11. The index of orthognathic functional treatment need accurately prioritises those patients already selected for orthognathic surgery within the NHS.

    PubMed

    Shah, Rupal; Breeze, John; Chand, Mohit; Stockton, Peter

    2016-06-01

    The index of orthognathic functional treatment need (IOFTN) is a newly-proposed system to help to prioritise patients for orthognathic treatment. The five categories are similar to those used in orthodontics, but include additional parameters such as sleep apnoea and facial asymmetry. The aim of this audit was to validate the index and find out the potential future implications, should such a system ever be adopted by commissioners. We calculated the IOFTN category of 100 consecutive patients who had orthognathic surgery between 2010-14 using clinical notes, photographs, study models, and radiographs, and determined the number in categories 4 or 5, analogous to the current indications for orthodontic treatment within the NHS. Sufficient clinical information was available to categorise 59/100 patients, and 56 of the 59 (95%) were in either category 4 or 5. All three of the remaining patients (in categories 1-3) who were operated on were treated because of the anticipated favourable impact on their quality of life. The IOFTN has been proposed for use in future commissioning of orthognathic services within the NHS, and this study has confirmed its efficacy in prioritising treatment accurately, with 95% of patients being in categories 4 or 5. We recommend that the orthognathic treatment index be adapted to include additional psychosocial assessment so that patients who fall into the lower functional categories are not automatically excluded from this potentially life-changing treatment. PMID:26935212

  12. Mobile Delivery of Treatment for Alcohol Use Disorders

    PubMed Central

    Quanbeck, Andrew; Chih, Ming-Yuan; Isham, Andrew; Johnson, Roberta; Gustafson, David

    2014-01-01

    Several systems for treating alcohol-use disorders (AUDs) exist that operate on mobile phones. These systems are categorized into four groups: text-messaging monitoring and reminder systems, text-messaging intervention systems, comprehensive recovery management systems, and game-based systems. Text-messaging monitoring and reminder systems deliver reminders and prompt reporting of alcohol consumption, enabling continuous monitoring of alcohol use. Text-messaging intervention systems additionally deliver text messages designed to promote abstinence and recovery. Comprehensive recovery management systems use the capabilities of smart-phones to provide a variety of tools and services that can be tailored to individuals, including in-the-moment assessments and access to peer discussion groups. Game-based systems engage the user using video games. Although many commercial applications for treatment of AUDs exist, few (if any) have empirical evidence of effectiveness. The available evidence suggests that although texting-based applications may have beneficial effects, they are probably insufficient as interventions for AUDs. Comprehensive recovery management systems have the strongest theoretical base and have yielded the strongest and longest-lasting effects, but challenges remain, including cost, understanding which features account for effects, and keeping up with technological advances. PMID:26259005

  13. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment.

    PubMed

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-05-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

  14. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

    PubMed Central

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-01-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

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

    PubMed

    Gertz, Zachary M; Wilensky, Robert L

    2011-12-01

    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

  16. Faint electric treatment-induced rapid and efficient delivery of extraneous hydrophilic molecules into the cytoplasm.

    PubMed

    Hasan, Mahadi; Nishimoto, Akinori; Ohgita, Takashi; Hama, Susumu; Kashida, Hiromu; Asanuma, Hiroyuki; Kogure, Kentaro

    2016-04-28

    Effective delivery of extraneous molecules into the cytoplasm of the target cells is important for several drug therapies. Previously, we showed effective in vivo transdermal delivery of naked siRNA into skin cells induced by faint electric treatment (ET) iontophoresis, and significant suppression of target mRNA levels (Kigasawa et al., Int. J. Pharm., 2010). This result indicates that electricity promoted the delivery of siRNA into cytoplasm. In the present study, we analyzed the intracellular delivery of naked anti-luciferase siRNA by faint ET, and found that the luciferase activity of cells expressing luciferase was reduced by in vitro ET like in vivo iontophoresis. Cellular uptake of fluorescent-label siRNA was increased by ET, while low temperature exposure, macropinocytosis inhibitor amiloride and caveolae-mediated endocytosis inhibitor filipin significantly prevented siRNA uptake. These results indicate that the cellular uptake mechanism involved endocytosis. In addition, voltage sensitive fluorescent dye DiBAC4 (3) penetration was increased by ET, and the transient receptor potential channel inhibitor SKF96365 reduced siRNA uptake, suggesting that faint ET reduced membrane potentials by changing intracellular ion levels. Moreover, to analyze cytoplasmic delivery, we used in-stem molecular beacon (ISMB), which fluoresces upon binding to target mRNA in the cytoplasm. Surprisingly, cytoplasmic ISMB fluorescence appeared rapidly and homogeneously after ET, indicating that cytoplasmic delivery is markedly enhanced by ET. In conclusion, we demonstrated for the first time that faint ET can enhance cellular uptake and cytoplasmic delivery of extraneous molecules. PMID:26944781

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

    SciTech Connect

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

    2015-01-15

    Purpose: An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. Methods: The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system was designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system’s performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery

  18. Accurate treatments of electrostatics for computer simulations of biological systems: A brief survey of developments and existing problems

    NASA Astrophysics Data System (ADS)

    Yi, Sha-Sha; Pan, Cong; Hu, Zhong-Han

    2015-12-01

    Modern computer simulations of biological systems often involve an explicit treatment of the complex interactions among a large number of molecules. While it is straightforward to compute the short-ranged Van der Waals interaction in classical molecular dynamics simulations, it has been a long-lasting issue to develop accurate methods for the longranged Coulomb interaction. In this short review, we discuss three types of methodologies for the accurate treatment of electrostatics in simulations of explicit molecules: truncation-type methods, Ewald-type methods, and mean-field-type methods. Throughout the discussion, we brief the formulations and developments of these methods, emphasize the intrinsic connections among the three types of methods, and focus on the existing problems which are often associated with the boundary conditions of electrostatics. This brief survey is summarized with a short perspective on future trends along the method developments and applications in the field of biological simulations. Project supported by the National Natural Science Foundation of China (Grant Nos. 91127015 and 21522304) and the Open Project from the State Key Laboratory of Theoretical Physics, and the Innovation Project from the State Key Laboratory of Supramolecular Structure and Materials.

  19. Local Drug Delivery Systems in the Treatment of Periodontitis: A Literature Review.

    PubMed

    Da Rocha, Huberth Alexandre Júnior; Silva, Camila Ferreira; Santiago, Fernanda Lopes; Martins, Ludiele Gonçalves; Dias, Pâmella Coelho; De Magalhães, Denildo

    2015-07-01

    In order to complement non-surgical therapy in periodontitis, there are multiple options of antimicrobials, such as metronidazole, chlorhexidine, minocycline, doxycycline and tetracycline, which can be locally delivered into the mucosa. These drugs are used in periodontal pockets and can inhibit or eliminate periodontopathogenic microorganisms as well as modulate the inflammatory response of tissues. However, limited data are available concerning the relationship between effect, efficacy and clinical status of the periodontium. This review aims to evaluate the effect and the efficacy of five types of local drug delivery systems in clinical parameters of periodontology. Researched papers using MEDLINE via PubMed, and LILACS databases related to five types of local drug delivery systems as chlorhexidine gluconate, doxycycline hyclate, metronidazole gel, minocycline ointment and tetracycline fibers, were reviewed aiming to address the mechanism of action and the evidence of clinical effectiveness of adjunctive use of these antimicrobials following surgical and/or non-surgical therapies. Inclusion criteria defined that articles must be randomized controlled trials performed in humans and published between 1996 and 2014. The adjunctive use of local drug delivery systems with controlled release properties may provide a defined, but limited, beneficial response on periodontal pockets. Furthermore, local drug delivery as an active treatment or maintenance therapy depends on clinical findings, responses to treatment described in the literature, desired clinical outcomes, and patients' dental and medical histories, including their past usage of antimicrobials. PMID:26373225

  20. Cervical cancer treatment with a locally insertable controlled release delivery system

    PubMed Central

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

    2006-01-01

    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 μg/day to 46.9±10.0 μg/day) and diffusion analysis based upon diffusion through a porous structure (Dapp from 1.3±0.5×10−9 cm2/s to 5.8±0.3×10−12 cm2/s). The devices were tested for in vitro activity and found to be effective against both HPV positive and HPV negative cervical cancer cell lines. Preliminary studies indicate that this delivery system would be a good candidate for investigation as a choice of treatment in cervical cancers. PMID:17034891

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Sengbusch, Evan R.

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

  3. Volumetric Modulated Arc Therapy for Spine Radiosurgery: Superior Treatment Planning and Delivery Compared to Static Beam Intensity Modulated Radiotherapy

    PubMed Central

    Zach, Leor; Tsvang, Lev; Alezra, Dror; Ben Ayun, Maoz

    2016-01-01

    Purpose. Spine stereotactic radiosurgery (SRS) delivers an accurate and efficient high radiation dose to vertebral metastases in 1–5 fractions. We aimed to compare volumetric modulated arc therapy (VMAT) to static beam intensity modulated radiotherapy (IMRT) for spine SRS. Methods and Materials. Ten spine lesions of previously treated SRS patients were planned retrospectively using both IMRT and VMAT with a prescribed dose of 16 Gy to 100% of the planning target volume (PTV). The plans were compared for conformity, homogeneity, treatment delivery time, and safety (spinal cord dose). Results. All evaluated parameters favored the VMAT plan over the IMRT plans. Dmin in the IMRT was significantly lower than in the VMAT plan (7.65 Gy/10.88 Gy, p < 0.001), the Dice Similarity Coefficient (DSC) was found to be significantly better for the VMAT plans compared to the IMRT plans (0.77/0.58, resp., p  value < 0.01), and an almost 50% reduction in the net treatment time was calculated for the VMAT compared to the IMRT plans (6.73 min/12.96 min, p < 0.001). Conclusions. In our report, VMAT provides better conformity, homogeneity, and safety profile. The shorter treatment time is a major advantage and not only provides convenience to the painful patient but also contributes to the precision of this high dose radiation therapy. PMID:26885513

  4. Chitosan and glyceryl monooleate nanostructures containing gemcitabine: potential delivery system for pancreatic cancer treatment.

    PubMed

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

    2010-03-01

    The objectives of this study are to enhance cellular accumulation of gemcitabine with chitosan/glyceryl monooleate (GMO) nanostructures, and to provide significant increase in cell death of human pancreatic cancer cells in vitro. The delivery system was prepared by a multiple emulsion solvent evaporation method. The nanostructure topography, size, and surface charge were determined by atomic force microscopy (AFM), and a zetameter. The cellular accumulation, cellular internalization and cytotoxicity of the nanostructures were evaluated by HPLC, confocal microscopy, or MTT assay in Mia PaCa-2 and BxPC-3 cells. The average particle diameter for 2% and 4% (w/w) drug loaded delivery system were 382.3 +/- 28.6 nm, and 385.2 +/- 16.1 nm, respectively with a surface charge of +21.94 +/- 4.37 and +21.23 +/- 1.46 mV. The MTT cytotoxicity dose-response studies revealed the placebo at/or below 1 mg/ml has no effect on MIA PaCa-2 or BxPC-3 cells. The delivery system demonstrated a significant decrease in the IC50 (3 to 4 log unit shift) in cell survival for gemcitabine nanostructures at 72 and 96 h post-treatment when compared with a solution of gemcitabine alone. The nanostructure reported here can be resuspended in an aqueous medium that demonstrate increased effective treatment compared with gemcitabine treatment alone in an in vitro model of human pancreatic cancer. The drug delivery system demonstrates capability to entrap both hydrophilic and hydrophobic compounds to potentially provide an effective treatment option in human pancreatic cancer. PMID:20238190

  5. A novel polymeric chlorhexidine delivery device for the treatment of periodontal disease.

    PubMed

    Yue, Isaac C; Poff, Jason; Cortés, María E; Sinisterra, Ruben D; Faris, Caroline B; Hildgen, Patrice; Langer, Robert; Shastri, V Prasad

    2004-08-01

    An implantable, anti-microbial delivery device for the treatment of periodontal disease has been developed. In this polymer-based delivery system, the encapsulation efficiency, release characteristics, and bioactivity of anti-microbial agent were controlled by the complexation of the drug with cyclodextrins of differing lipophilicity. Microparticles of poly(dl-lactic-co-glycolic acid) (PLGA) containing chlorhexidine (Chx) free base, chlorhexidine digluconate (Chx-Dg) and their association or inclusion complex with methylated-beta-cyclodextrin (MBCD) and hydroxypropyl-beta-cyclodextrin (HPBCD) were prepared by single emulsion, solvent evaporation technique. It was observed that encapsulation efficiency and release of the chlorhexidine derivatives from the microparticles was a function of the lipophilicity of the cyclodextrin. Complexation of the poorly water soluble Chx with the more hydrophilic HPBCD resulted in 62% higher encapsulation efficiency and longer duration of sustained release over a 2-week period than complexation with the more lipophilic MBCD. In contrast, the complexation of the more water-soluble derivative of chlorhexidine, Chx-Dg, with the more lipophilic MBCD improved encapsulation efficiency by 12% and prolonged its release in comparison to both the free Chx-Dg and its complex with HPBCD. Furthermore, it was observed that the initial burst effect could be diminished by complexation with CD. Preliminary studies have shown that the chlorhexidine released from PLGA chips is biologically active against bacterial population that is relevant in periodontitis (P. gingivalis and B. forsythus) and a healthy inhibition zone is maintained in agar plate assay over a period of at least a 1-week. The PLGA/CD delivery system described in this paper may prove useful for the localized delivery of chlorhexidine salts and other anti-microbial agents in the treatment of periodontal disease where prolonged-controlled delivery is desired. PMID:15020150

  6. Application of Convection-Enhanced Drug Delivery in the Treatment of Malignant Gliomas.

    PubMed

    Tykocki, Tomasz; Miękisiak, Grzegorz

    2016-06-01

    Convection-enhanced delivery (CED) is a promising new method of local drug delivery therapy for a diverse type of antitumor agents. CED offers significant advantages over systemic chemotherapy by bypassing the blood-brain barrier and obtaining adequate drug concentration with limited systemic toxicity. Actually, there is no effective treatment of malignant gliomas (MGs); survival rates remain poor despite decades of clinical trials. Conventional chemotherapy has been found to be minimally effective in the control of MG progression. CED involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered directly to the tumor using continuous, low-positive-pressure bulk flow. On the basis of the preclinical and clinical studies, we demonstrated that CED could produce effective drug delivery to large brain and tumor areas. However, clinical studies to date have not found any substantial improvement in overall survival in the treatment of MG. This overview presents up-to-date clinical results in the treatment of MG by the application of CED. PMID:26898499

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

    PubMed Central

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

    2014-01-01

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

  8. Curcumin loaded mesoporous silica: an effective drug delivery system for cancer treatment.

    PubMed

    Kotcherlakota, Rajesh; Barui, Ayan Kumar; Prashar, Sanjiv; Fajardo, Mariano; Briones, David; Rodríguez-Diéguez, Antonio; Patra, Chitta Ranjan; Gómez-Ruiz, Santiago

    2016-03-01

    In the present study, we report the delivery of anti-cancer drug curcumin to cancer cells using mesoporous silica materials. A series of mesoporous silica material based drug delivery systems (S2, S4 and S6) were first designed and developed through the amine functionalization of KIT-6, MSU-2 and MCM-41 followed by the loading of curcumin. The curcumin loaded materials were characterized with several physico-chemical techniques and thoroughly screened on cancer cells to evaluate their in vitro drug delivery efficacy. All the curcumin loaded silica materials exhibited higher cellular uptake and inhibition of cancer cell viability compared to pristine curcumin. The effective internalization of curcumin in cancer cells through the mesoporous silica materials initiated the generation of intracellular reactive oxygen species and the down regulation of poly ADP ribose polymerase (PARP) enzyme levels compared to free curcumin leading to the activation of apoptosis. This study shows that the anti-cancer activity of curcumin can be potentiated by loading onto mesoporous silica materials. Therefore, we strongly believe that mesoporous silica based curcumin loaded drug delivery systems may have future potential applications for the treatment of cancers. PMID:26674254

  9. Strategies for Delivery of Therapeutics into the Central Nervous System for Treatment of Lysosomal Storage Disorders

    PubMed Central

    Muro, Silvia

    2014-01-01

    Lysosomal storage disorders (LSDs) are a group of about fifty life-threatening conditions caused by genetic defects affecting lysosomal components. The underscoring molecular deficiency leads to widespread cellular dysfunction through most tissues in the body, including peripheral organs and the central nervous system (CNS). Efforts during the last few decades have rendered a remarkable advance regarding our knowledge, medical awareness, and early detection of these genetic defects, as well as development of several treatment modalities. Clinical and experimental strategies encompassing enzyme replacement, gene and cell therapies, substrate reduction, and chemical chaperones are showing considerable potential in attenuating the peripheral pathology. However, a major drawback has been encountered regarding the suboptimal impact of these approaches on the CNS pathology. Particular anatomical and biochemical constraints of this tissue pose a major obstacle to the delivery of therapeutics into the CNS. Approaches to overcome these obstacles include modalities of local administration, strategies to enhance the blood-CNS permeability, intranasal delivery, use of exosomes, and those exploiting targeting of transporters and transcytosis pathways in the endothelial lining. The later two approaches are being pursued at the time by coupling therapeutic agents to affinity moieties and drug delivery systems capable of targeting these natural transport routes. This approach is particularly promising, as using paths naturally active at this interface may render safe and effective delivery of LSD therapies into the CNS. PMID:24688886

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

    PubMed Central

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

    2011-01-01

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

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

    SciTech Connect

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

    2011-07-15

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

  12. Ungual and trans-ungual iontophoretic delivery of terbinafine for the treatment of onychomycosis.

    PubMed

    Nair, Anroop B; Kim, Hyun D; Chakraborty, Bireswar; Singh, Jagpal; Zaman, Muhammad; Gupta, Aditya; Friden, Phillip M; Murthy, S Narasimha

    2009-11-01

    The application of iontophoresis was demonstrated in the nail drug delivery of terbinafine (TH) recently. This study explored a systematic assessment of this approach to enhance the drug delivery using a novel topical formulation, and the subsequent release of TH from the drug loaded nails. For the first time, a nail on-agar plate model was used to study the release of drug from the iontophoresis (0.5 mA/cm(2)) loaded nails. In addition, the activity of the drug released from the drug loaded nail plate was studied against Trichophyton rubrum. An increase in applied current density and current duration enhanced the transport of TH into and through the nail plate. In vitro release of drug from the iontophoretic loaded nails into agar plates exhibited 2-phase release pattern. The amount of drug released in both of the in vitro models was comparable, and the nails loaded using iontophoresis continued to release levels of TH > 2 orders of magnitude above the minimum inhibitory concentration over at least 52 days. Results indicate that iontophoresis enhances the delivery of terbinafine into and through the nail plate and suggest that the use of this treatment approach could result in a safe and more efficacious outcome with less frequent treatments. PMID:19340887

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

    PubMed

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

    2016-02-01

    Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t₁/₂ (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB. PMID:27305759

  14. Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

    PubMed Central

    Khalin, Igor; Alyautdin, Renad; Kocherga, Ganna; Bakar, Muhamad Abu

    2015-01-01

    Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration. PMID:25995632

  15. Treatment of Acute Massive Pulmonary Embolism by Streptokinase during Labour and Delivery

    PubMed Central

    Hall, R. J. C.; Young, C.; Sutton, G. C.; Cambell, S.

    1972-01-01

    A 29-year-old woman sustained an acute massive pulmonary embolism in the 32nd week of pregnancy. Rapid clinical improvement followed the use of streptokinase. Treatment was continued for 41 hours, including labour and the first three hours after delivery. There was slow but severe postpartum haemorrhage. Partial uterine atony occurred, and may have been due, at least in part, to fibrin degradation products arising from thrombolysis. No adverse effects were noted in the baby. Our experience suggests that streptokinase may be given during labour but that an oxytocic agent may be needed; and that reversal of fibrinolysis before delivery is best achieved by the use of aprotinin (Trasylol) rather than aminocaproic acid. Imagesp647-a PMID:4539533

  16. Novel drug delivery systems in topical treatment of psoriasis: rigors and vigors.

    PubMed

    Katare, Om Prakash; Raza, Kaisar; Singh, Bhupinder; Dogra, Sunil

    2010-01-01

    Psoriasis is a chronic inflammatory skin disorder that may drastically impair the quality of life of a patient. Among the various modes of treatments for psoriasis, topical therapy is most commonly used in majority of patients. The topical formulations based on conventional excipients could serve the purpose only to a limited extent. With the advent of newer biocompatible and biodegradable materials like phospholipids, and cutting-edge drug delivery technologies like liposomes, solid lipid nanoparticles (SLNs), microemulsions, and nanoemulsions, the possibility to improve the efficacy and safety of the topical products has increased manifold. Improved understanding of the dermal delivery aspects and that of designing and developing diverse carrier systems have brought in further novelty in this approach. Substantial efforts and the consequent publications, patents and product development studies on the subject are the matter of interest and review of this article. However, majority of the work is related to the preclinical studies and demands further clinical assessment in psoriasis patients. PMID:21079304

  17. [Progress of different drug delivery route of vancomycin for the treatment of chronic osteomyelitis].

    PubMed

    Long, Y Z; Zhu, Z X; Yu, Y; Zhang, S M

    2016-09-01

    Chronic osteomyelitis (COM) is an infectious disease caused by methicillin-resistant Staphylococcus aureus (MRSA), the main characteristics of COM including local dead bone formation, soft tissue infection, and repeatedly attacks. As a sensitive antibiotic, vancomycin plays an important role in the therapy of COM caused by MRSA. Currently, drug treatment is divided into systemic and topical, systemic medication is given priority to intravenous drug delivery; local drug application including local delivery device and local antibiotics lavage and regional arterial perfusion. In practice, its validity depends on whether free drug concentration of vancomycin has riched the effective concentration in the organization. Nevertheless, low concentration lead to treatment failure and even induce drug-resistance bacteria, meanwhile high concentration may cause acute renal failure. So when using vancomycin for the treatment of chronic osteomyelitis, both drug resistance and renal toxicity is as the same important as the effectiveness. Systemic administration is a targeting weak way and has many complications; topical medicate effect on the lesion can be targeted, it would be an effective way in the future treatment of COM. Different methods of delivering vancomycin have great influence on local drug concentration, which makes it become the most important factor on local drug concentration of COM. PMID:27587217

  18. Potential of targeted drug delivery system for the treatment of bone metastasis.

    PubMed

    Vinay, Raichur; KusumDevi, V

    2016-01-01

    Bone metastasis is a devastating complication of cancer that requires an immediate attention. Although our understanding of the metastatic process has improved over the years, yet a number of questions still remain unanswered, and more research is required for complete understanding of the skeletal consequences of metastasis. Furthermore, as no effective treatments are available for some of the most common skeleton disorders such as arthritis, osteoarthritis, osteosarcoma and metastatic bone cancer, there is an urgent need to develop new drugs and drug delivery systems for safe and efficient clinical treatments. Hence this article describes the potential of targeted delivery platforms aimed specifically at bone metastasized tumors. The review gives a brief understanding of the proposed mechanisms of metastasis and focuses primarily on the targeting moieties such as bisphosphonates, which represent the current gold standard in bone metastasis therapies. Special focus has been given to the targeted nanoparticulate systems for treating bone metastasis and its future. Also highlighted are some of the therapeutic targets that can be exploited for designing therapies for bone metastasis. Some of the patented molecules for bone metastasis prevention and treatment have also been discussed. Recently proposed HIFU-CHEM, which utilizes High Intensity Focused ultrasound (HIFU) guided by MRI in combination with temperature-sensitive nanomedicines has also been briefed. The study has been concluded with a focus on the innovations requiring an immediate attention that could improve the treatment modality of bone metastasis. PMID:24839990

  19. SU-E-J-17: Intra-Fractional Prostate Movement Correction During Treatment Delivery Period for Prostate Cancer Using the Intra-Fractional Orthogonal KV-MV Image Pairs

    SciTech Connect

    Zhang, J; Azawi, S; Cho-Lim, J; Wei, R; Williams, R; Frank, E

    2015-06-15

    Purpose: To evaluate the intra-fractional prostate movement range during the beam delivery and implement new IGRT method to correct the prostate movement during the hypofractionated prostate treatment delivery. Methods: To evaluate the prostate internal motion range during the beam delivery, 11 conventional treatments were utilized. Two-arc RapidArc plans were used for the treatment delivery. Orthogonal KV imaging is performed in the middle of the treatment to correct intra-fractional prostate movement. However, it takes gantry-mounted on-board imaging system relative long time to finish the orthogonal KV imaging because of gantry rotation. To avoid gantry movement and accelerate the IGRT processing time, orthogonal KV-MV image pair is tested using the OBI daily QA Cube phantom. Results: The average prostate movement between two orthogonal KV image pairs was 0.38cm (0.20cm ∼ 0.85cm). And the interval time between them was 6.71 min (4.64min ∼ 9.22 min). 2-arc beam delivery time is within 3 minutes for conventional RapidArc treatment delivery. Hypofractionated treatment or SBRT need 4 partial arc and possible non-coplanar technology, which need much longer beam delivery time. Therefore prostate movement might be larger. New orthogonal KV-MV image pair is a new method to correct the prostate movement in the middle of the beam delivery if real time tracking method is not available. Orthogonal KV-MV image pair doesn’t need gantry rotation. Images were acquired quickly which minimized possible new prostate movement. Therefore orthogonal KV-MV image pair is feasible for IGRT. Conclusion: Hypofractionated prostate treatment with less PTV margin always needs longer beam delivery time. Therefore prostate movement correction during the treatment delivery is critical. Orthogonal KV-MV imaging pair is efficient and accurate to correct the prostate movement during treatment beam delivery. Due to limited fraction number and high dose per fraction, the MV imaging dose is

  20. Can dental registrants use the Index of Orthodontic Treatment Need accurately? Part 1: Knowledge of IOTN among dental registrants.

    PubMed

    Jawad, Z; Bates, C; Hodge, T

    2016-05-27

    Aim To determine whether dental registrants can use the dental health component (DHC) and aesthetic component (AC) of the Index of Orthodontic Treatment Need (IOTN) 'accurately' to an acceptable level of agreement and diagnostic validity.Method Participants from six different registrant groups were asked to score the IOTN for 14 cases based on study models and photographs as well as completing a short questionnaire. Participants in the study were all recruited at study days and annual conferences. The main outcome measures include the different registrant groups IOTN scores compared to expert panel scores using kappa statistics. To assess for diagnostic validity, individual participants sensitivity and specificity scores were calculated.Result Overall, 229 registrants took part in the study. For the DHC the specialist orthodontist (SO), postgraduate orthodontic student (PGOS) and the qualified orthodontic therapist (QOT) groups achieved a mean kappa ≥0.60 indicating 'acceptable' agreement with the expert panel scores. The dental foundation trainee (DFT) and general dental practitioner (GDP) group achieved a mean kappa of 0.20 and 0.22 respectively indicating poor and fair agreement. The student orthodontic therapist (SOT) group achieved a mean kappa of 0.55 indicating moderate agreement. For the AC none of the registrant groups achieved an acceptable level of agreement with the mean kappa scores for the different groups ranging from kappa 0.13-0.21, indicating poor to fair agreement.Conclusion Overall agreement for the DHC was varied for the different registrant groups ranging from fair to substantial agreement. Registrants were better at applying the DHC compared to the AC with agreement ranging from poor to fair. More needs to done to help registrants use the IOTN more 'accurately'. PMID:27228933

  1. Use of Liposomes as Drug Delivery Vehicles for Treatment of Melanoma

    PubMed Central

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

    2009-01-01

    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. PMID:19493316

  2. Preclinical evaluation of gene delivery methods for the treatment of loco-regional disease in breast cancer.

    PubMed

    Rajendran, Simon; O'Hanlon, Deirdre; Morrissey, David; O'Donovan, Tracey; O'Sullivan, Gerald C; Tangney, Mark

    2011-04-01

    Preclinical results with various gene therapy strategies indicate significant potential for new cancer treatments. However, many therapeutics fail at clinical trial, often due to differences in tissue physiology between animal models and humans, and tumor phenotype variation. Clinical data relevant to treatment strategies may be generated prior to clinical trial through experimentation using intact patient tissue ex vivo. We developed a novel tumor slice model culture system that is universally applicable to gene delivery methods, using a realtime luminescence detection method to assess gene delivery. Methods investigated include viruses (adenovirus [Ad] and adeno-associated virus), lipofection, ultrasound (US), electroporation and naked DNA. Viability and tumor populations within the slices were well maintained for seven days, and gene delivery was qualitatively and quantitatively examinable for all vectors. Ad was the most efficient gene delivery vector with transduction efficiency >50%. US proved the optimal non-viral gene delivery method in human tumor slices. The nature of the ex vivo culture system permitted examination of specific elements. Parameters shown to diminish Ad gene delivery included blood, regions of low viability and secondary disease. US gene delivery was significantly reduced by blood and skin, while tissue hyperthermia improved gene delivery. US achieved improved efficacy for secondary disease. The ex vivo model was also suitable for examination of tissue-specific effects on vector expression, with Ad expression mediated by the CXCR4 promoter shown to provide a tumor selective advantage over the ubiquitously active cytomegalovirus promoter. In conclusion, this is the first study incorporating patient tissue models in comparing gene delivery from various vectors, providing knowledge on cell-type specificity and examining the crucial biological factors determining successful gene delivery. The results highlight the importance of in

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

    PubMed Central

    Kim, Pyung-Hwan; Kim, Sung Wan

    2012-01-01

    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

  4. Microparticles as controlled drug delivery carrier for the treatment of ulcerative colitis: A brief review.

    PubMed

    Nidhi; Rashid, Muzamil; Kaur, Veerpal; Hallan, Supandeep Singh; Sharma, Saurabh; Mishra, Neeraj

    2016-07-01

    Ulcerative colitis is the chronic relapsing multifactorial gastrointestinal inflammatory bowel disease, which is characterized by bloody or mucus diarrhea, tenesmus, bowel dystension, anemia. The annual incidence of ulcerative colitis in Asia, North America and Europe was found to be 6.3, 19.2 and 24.3 per 100,000 person-years. The major challenge in the treatment of ulcerative colitis is appropriate local targeting and drug related side-effects. To overcome these challenges, microparticulate systems seem to be a promising approach for controlled and sustained drug release after oral administration. The main goal of this article is to explore the role of microparticles in ulcerative colitis for the appropriate targeting of drugs to colon. There are different approaches which have been studied over the last decade, including prodrugs, polymeric approach, time released system, pH sensitive system, which show the site specific drug delivery to colon. Among these approaches, microparticulate drug delivery system has been gaining an immense importance for local targeting of drug to colon at a controlled and sustained rate. Combined approaches such as pH dependent and time dependent system provide the maximum release of drug into colon via oral route. This article embraces briefly about pathophysiology, challenges and polymeric approaches mainly multiparticulate systems for site specific drug delivery to colon in sustained and controlled manner so that drug related side-effects by reducing dosage frequency can be minimized. PMID:27330377

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

    PubMed Central

    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

    Controlled-release delivery of 6-β-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. PMID:20166200

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

    PubMed

    Betts, Corinne A; Wood, Matthew J A

    2013-01-01

    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

  7. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma

    PubMed Central

    Hsueh, Chung-Tzu; Selim, Julie H; Tsai, James Y; Hsueh, Chung-Tsen

    2016-01-01

    Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma. PMID:27610018

  8. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma.

    PubMed

    Hsueh, Chung-Tzu; Selim, Julie H; Tsai, James Y; Hsueh, Chung-Tsen

    2016-08-21

    Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma. PMID:27610018

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

    Many tumor cells demonstrate hyperradiosensitivity at doses below ˜50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (˜20 cGy/pulse and effective dose rate 6.7 cGy min-1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min-1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (˜20 cGy arc-1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min-1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10-1.38 HI 1.04-1.10) and the VMAT (CI 1.08-1.26 HI 1.05-1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of

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

    PubMed

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

    2013-11-21

    Many tumor cells demonstrate hyperradiosensitivity at doses below ~50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (~20 cGy/pulse and effective dose rate 6.7 cGy min−1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min−1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (~20 cGy arc−1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min−1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10–1.38; HI 1.04–1.10) and the VMAT (CI 1.08–1.26; HI 1.05–1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the

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

    PubMed

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

    2005-11-01

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

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

    NASA Astrophysics Data System (ADS)

    Balivada, Sivasai

    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 (rCasp3V

  13. Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer's disease.

    PubMed

    Kim, Ji-Yeon; Han, Mee-Ree; Kim, Yong-Han; Shin, Seung-Woo; Nam, Su-Youn; Park, Jung-Hwan

    2016-08-01

    Donepezil hydrochloride (DPH) is often used in the treatment of Alzheimer's disease. A new treatment method was developed by encapsulating high DPH content in the tips of dissolving microneedles for rapid, transdermal delivery of a predetermined dose of DPH. The microneedles were prepared by a micromolding method using a hydroxy-propyl-methyl-cellulose (HPMC)-ethanol/water mixture (80:20, v/v) for the tips and carboxy-methyl cellulose (CMC)-water for the base of the needles. The micromolding method involved centrifuging a DPH-HPMC-ethanol/water mixture at 10°C to obtain tips with sufficient mechanical strength. To test their mechanical strength, microneedles with different DPH content were inserted into porcine skin. Then the amount of DPH encapsulated in the microneedles was measured using high-performance liquid chromatography. The efficiency of administering DPH tip-loaded microneedles was investigated using four administrations of a pharmacokinetic test: (1) two oral administration groups (283μg/kg and 692μg/kg) and (2) two microneedle administration groups (283μg/kg and 692μg/kg). High DPH content (up to 78%, w/w) was encapsulated in the microneedle tips without serious loss of mechanical strength by using a mixture of hydroxy-propyl-methyl-cellulose (HPMC) and ethanol/water mixture (80:20, v/v). Because of the distribution of DPH in the tips, 95% of the DPH was delivered into porcine skin after 5min of insertion. As measured by Cmax and AUC, transdermal delivery of DPH tip-loaded microneedles was more effective compared to oral administration of the same dose of DPH. Transdermal delivery could replace oral administration of DPH. PMID:27288938

  14. Ethosomes-based topical delivery system of antihistaminic drug for treatment of skin allergies.

    PubMed

    Goindi, Shishu; Dhatt, Bhavnita; Kaur, Amanpreet

    2014-01-01

    Cetirizine is indicated for the treatment of allergic conditions such as insect bites and stings, atopic and contact dermatitis, eczema, urticaria. This investigation deals with development of a novel ethosome-based topical formulation of cetirizine dihydrochloride for effective delivery. The optimised formulation consisting of drug, phospholipon 90 G™ and ethanol was characterised for drug content, entrapment efficiency, pH, vesicular size, spreadability and rheological behaviour. The ex vivo permeation studies through mice skin showed highest permeation flux (16.300 ± 0.300 µg/h/cm(2)) and skin retention (20.686 ± 0.517 µg/cm(2)) for cetirizine-loaded ethosomal vesicles as compared to conventional formulations. The in vivo pharmacodynamic evaluation of optimised formulation was assessed against oxazolone-induced atopic dermatitis (AD) in mice. The parameters evaluated were reduction in scratching score, erythema score, skin hyperplasia and dermal eosinophil count. Our results suggest that ethosomes are effective carriers for dermal delivery of antihistaminic drug, cetirizine, for the treatment of AD. PMID:24963956

  15. Local delivery methods of therapeutic agents in the treatment of diffuse intrinsic brainstem gliomas.

    PubMed

    Goodwin, C Rory; Xu, Risheng; Iyer, Rajiv; Sankey, Eric W; Liu, Ann; Abu-Bonsrah, Nancy; Sarabia-Estrada, Rachel; Frazier, James L; Sciubba, Daniel M; Jallo, George I

    2016-03-01

    Brainstem gliomas comprise 10-20% of all pediatric central nervous system (CNS) tumors and diffuse intrinsic pontine gliomas (DIPGs) account for the majority of these lesions. DIPG is a rapidly progressive disease with almost universally fatal outcomes and a median survival less than 12 months. Current standard-of-care treatment for DIPG includes radiation therapy, but its long-term survival effects are still under debate. Clinical trials investigating the efficacy of systemic administration of various therapeutic agents have been associated with disappointing outcomes. Recent efforts have focused on improvements in chemotherapeutic agents employed and in methods of localized and targeted drug delivery. This review provides an update on current preclinical and clinical studies investigating treatment options for brainstem gliomas. PMID:26849840

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

    SciTech Connect

    Fraass, Benedick A.

    2008-05-01

    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.

  17. Feasibility of Two Modes of Treatment Delivery for Child Anxiety in Primary Care

    PubMed Central

    Chavira, Denise A.; Drahota, Amy; Garland, Ann; Roesch, Scott; Garcia, Maritza; Stein, Murray B.

    2014-01-01

    In this study, we examine the feasibility of cognitive behavior therapy (CBT) for children with anxiety in primary care, using two modes of treatment delivery. A total of 48 parents and youth (8–13) with anxiety disorders were randomly assigned to receive 10-sessions of CBT either delivered by a child anxiety specialist in the primary care clinic or implemented by the parent with therapist support by telephone (i.e., face-to-face or therapist-supported bibliotherapy). Feasibility outcomes including satisfaction, barriers to treatment participation, safety, and dropout were assessed. Independent evaluators, blind to treatment condition, administered the Anxiety Disorders Interview Schedule for Children (ADIS) and the Clinical Global Impression of Improvement (CGI-I) at baseline, post-treatment and 3-month follow-up; clinical self-report questionnaires were also administered. Findings revealed high satisfaction, low endorsement of barriers, low drop out rates, and no adverse events across the two modalities. According to the CGI-I, 58.3%–75% of participants were considered responders (i.e., much or very much improved) at the various time points. Similar patterns were found for remission from “primary anxiety disorder” and “all anxiety disorders” as defined by the ADIS. Clinically significant improvement was seen on the various parent and child self-report measures of anxiety. Findings suggest that both therapy modalities are feasible and associated with significant treatment gains in the primary care setting. PMID:25075802

  18. Nanomedicine and drug delivery strategies for treatment of inflammatory bowel disease

    PubMed Central

    Takedatsu, Hidetoshi; Mitsuyama, Keiichi; Torimura, Takuji

    2015-01-01

    Crohn’s disease and ulcerative colitis are two important categories of human inflammatory bowel disease (IBD). Because the precise mechanisms of the inflammation and immune responses in IBD have not been fully elucidated, the treatment of IBD primarily aims to inhibit the pathogenic factors of the inflammatory cascade. Inconsistencies exist regarding the response and side effects of the drugs that are currently used to treat IBD. Recent studies have suggested that the use of nanomedicine might be advantageous for the treatment of intestinal inflammation because nano-sized molecules can effectively penetrate epithelial and inflammatory cells. We reviewed nanomedicine treatments, such as the use of small interfering RNAs, antisense oligonucleotides, and anti-inflammatory molecules with delivery systems in experimental colitis models and clinical trials for IBD based on a systematic search. The efficacy and usefulness of the treatments reviewed in this manuscript have been demonstrated in experimental colitis models and clinical trials using various types of nanomedicine. Nanomedicine is expected to become a new therapeutic approach to the treatment of IBD. PMID:26525603

  19. Successful remote delivery of a treatment for phonological alexia via telerehab.

    PubMed

    Getz, Heidi; Snider, Sarah; Brennan, David; Friedman, Rhonda

    2016-08-01

    A growing body of literature supports the effectiveness of the remote delivery of rehabilitation services, i.e., telerehab. Aphasia treatment is particularly well suited for telerehab because of the verbal and visual nature of speech-language therapy, but scientific research investigating aphasia telerehab is in its infancy. No studies to date have evaluated whether treatment of acquired reading disorders by a live clinician can be feasibly, effectively, or efficiently conducted via telerehab. Here we address this gap in the literature by reporting our success remotely remediating the reading deficits of two participants with phonological alexia. We adapted for the telerehab setting a previously validated treatment for phonological alexia (Friedman, Sample, & Lott, 2002 ), which uses a paired-associate design to train reading of problematic words. Both telerehab participants significantly improved their reading of trained words in similar time frames as previous participants (Friedman et al., 2002 ; Kurland et al., 2008 ; Lott, Sample, Oliver, Lacey, & Friedman, 2008 ); furthermore, both participants reported high satisfaction with the telerehab setting. Although telerehab with alexic patients poses unique challenges, we conclude that treatment for alexia via telerehab is nevertheless feasible, may be equally effective as in-person treatment, and saves substantial resources for participants as well as clinicians. PMID:26018197

  20. Nanomedicine and drug delivery strategies for treatment of inflammatory bowel disease.

    PubMed

    Takedatsu, Hidetoshi; Mitsuyama, Keiichi; Torimura, Takuji

    2015-10-28

    Crohn's disease and ulcerative colitis are two important categories of human inflammatory bowel disease (IBD). Because the precise mechanisms of the inflammation and immune responses in IBD have not been fully elucidated, the treatment of IBD primarily aims to inhibit the pathogenic factors of the inflammatory cascade. Inconsistencies exist regarding the response and side effects of the drugs that are currently used to treat IBD. Recent studies have suggested that the use of nanomedicine might be advantageous for the treatment of intestinal inflammation because nano-sized molecules can effectively penetrate epithelial and inflammatory cells. We reviewed nanomedicine treatments, such as the use of small interfering RNAs, antisense oligonucleotides, and anti-inflammatory molecules with delivery systems in experimental colitis models and clinical trials for IBD based on a systematic search. The efficacy and usefulness of the treatments reviewed in this manuscript have been demonstrated in experimental colitis models and clinical trials using various types of nanomedicine. Nanomedicine is expected to become a new therapeutic approach to the treatment of IBD. PMID:26525603

  1. Sui generis: gene therapy and delivery systems for the treatment of glioblastoma

    PubMed Central

    Kane, J. Robert; Miska, Jason; Young, Jacob S.; Kanojia, Deepak; Kim, Julius W.; Lesniak, Maciej S.

    2015-01-01

    Gene therapy offers a multidimensional set of approaches intended to treat and cure glioblastoma (GBM), in combination with the existing standard-of-care treatment (surgery and chemoradiotherapy), by capitalizing on the ability to deliver genes directly to the site of neoplasia to yield antitumoral effects. Four types of gene therapy are currently being investigated for their potential use in treating GBM: (i) suicide gene therapy, which induces the localized generation of cytotoxic compounds; (ii) immunomodulatory gene therapy, which induces or augments an enhanced antitumoral immune response; (iii) tumor-suppressor gene therapy, which induces apoptosis in cancer cells; and (iv) oncolytic virotherapy, which causes the lysis of tumor cells. The delivery of genes to the tumor site is made possible by means of viral and nonviral vectors for direct delivery of therapeutic gene(s), tumor-tropic cell carriers expressing therapeutic gene(s), and “intelligent” carriers designed to increase delivery, specificity, and tumoral toxicity against GBM. These vehicles are used to carry genetic material to the site of pathology, with the expectation that they can provide specific tropism to the desired site while limiting interaction with noncancerous tissue. Encouraging preclinical results using gene therapies for GBM have led to a series of human clinical trials. Although there is limited evidence of a therapeutic benefit to date, a number of clinical trials have convincingly established that different types of gene therapies delivered by various methods appear to be safe. Due to the flexibility of specialized carriers and genetic material, the technology for generating new and more effective therapies already exists. PMID:25746089

  2. Bolaamphiphile-based nanocomplex delivery of phosphorothioate gapmer antisense oligonucleotides as a treatment for Clostridium difficile

    PubMed Central

    Hegarty, John P; Krzeminski, Jacek; Sharma, Arun K; Guzman-Villanueva, Diana; Weissig, Volkmar; Stewart, David B

    2016-01-01

    Despite being a conceptually appealing alternative to conventional antibiotics, a major challenge toward the successful implementation of antisense treatments for bacterial infections is the development of efficient oligonucleotide delivery systems. Cationic vesicles (bolasomes) composed of dequalinium chloride (“DQAsomes”) have been used to deliver plasmid DNA across the cardiolipin-rich inner membrane of mitochondria. As cardiolipin is also a component of many bacterial membranes, we investigated the application of cationic bolasomes to bacteria as an oligonucleotide delivery system. Antisense sequences designed in silico to target the expression of essential genes of the bacterial pathogen, Clostridium difficile, were synthesized as 2′-O-methyl phosphorothioate gapmer antisense oligonucleotides (ASO). These antisense gapmers were quantitatively assessed for their ability to block mRNA translation using luciferase reporter and C. difficile protein expression plasmid constructs in a coupled transcription–translation system. Cationic bolaamphiphile compounds (dequalinium derivatives) of varying alkyl chain length were synthesized and bolasomes were prepared via probe sonication of an aqueous suspension. Bolasomes were characterized by particle size distribution, zeta potential, and binding capacities for anionic oligonucleotide. Bolasomes and antisense gapmers were combined to form antisense nanocomplexes. Anaerobic C. difficile log phase cultures were treated with serial doses of gapmer nanocomplexes or equivalent amounts of empty bolasomes for 24 hours. Antisense gapmers for four gene targets achieved nanomolar minimum inhibitory concentrations for C. difficile, with the lowest values observed for oligonucleotides targeting polymerase genes rpoB and dnaE. No inhibition of bacterial growth was observed from treatments at matched dosages of scrambled gapmer nanocomplexes or plain, oligonucleotide-free bolasomes compared to untreated control cultures. We

  3. Bolaamphiphile-based nanocomplex delivery of phosphorothioate gapmer antisense oligonucleotides as a treatment for Clostridium difficile.

    PubMed

    Hegarty, John P; Krzeminski, Jacek; Sharma, Arun K; Guzman-Villanueva, Diana; Weissig, Volkmar; Stewart, David B

    2016-01-01

    Despite being a conceptually appealing alternative to conventional antibiotics, a major challenge toward the successful implementation of antisense treatments for bacterial infections is the development of efficient oligonucleotide delivery systems. Cationic vesicles (bolasomes) composed of dequalinium chloride ("DQAsomes") have been used to deliver plasmid DNA across the cardiolipin-rich inner membrane of mitochondria. As cardiolipin is also a component of many bacterial membranes, we investigated the application of cationic bolasomes to bacteria as an oligonucleotide delivery system. Antisense sequences designed in silico to target the expression of essential genes of the bacterial pathogen, Clostridium difficile, were synthesized as 2'-O-methyl phosphorothioate gapmer antisense oligonucleotides (ASO). These antisense gapmers were quantitatively assessed for their ability to block mRNA translation using luciferase reporter and C. difficile protein expression plasmid constructs in a coupled transcription-translation system. Cationic bolaamphiphile compounds (dequalinium derivatives) of varying alkyl chain length were synthesized and bolasomes were prepared via probe sonication of an aqueous suspension. Bolasomes were characterized by particle size distribution, zeta potential, and binding capacities for anionic oligonucleotide. Bolasomes and antisense gapmers were combined to form antisense nanocomplexes. Anaerobic C. difficile log phase cultures were treated with serial doses of gapmer nanocomplexes or equivalent amounts of empty bolasomes for 24 hours. Antisense gapmers for four gene targets achieved nanomolar minimum inhibitory concentrations for C. difficile, with the lowest values observed for oligonucleotides targeting polymerase genes rpoB and dnaE. No inhibition of bacterial growth was observed from treatments at matched dosages of scrambled gapmer nanocomplexes or plain, oligonucleotide-free bolasomes compared to untreated control cultures. We describe

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

    PubMed

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

    2008-09-01

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

  5. Investigation of Plasma Treatment on Micro-Injection Moulded Microneedle for Drug Delivery.

    PubMed

    Nair, Karthik; Whiteside, Benjamin; Grant, Colin; Patel, Rajnikant; Tuinea-Bobe, Cristina; Norris, Keith; Paradkar, Anant

    2015-01-01

    Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA. PMID:26529005

  6. Investigation of Plasma Treatment on Micro-Injection Moulded Microneedle for Drug Delivery

    PubMed Central

    Nair, Karthik; Whiteside, Benjamin; Grant, Colin; Patel, Rajnikant; Tuinea-Bobe, Cristina; Norris, Keith; Paradkar, Anant

    2015-01-01

    Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA. PMID:26529005

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

    PubMed

    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

    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. PMID:24675359

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

    PubMed Central

    Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2012-01-01

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

  9. Biodegradable implantable fluconazole delivery rods designed for the treatment of fungal osteomyelitis: influence of gamma sterilization.

    PubMed

    Soriano, I; Martín, A Y; Evora, C; Sánchez, E

    2006-06-01

    Fluconazole poly(D,L-lactic) acid (PLA) and poly(L-lactic) acid (L-PLA) implantable delivery rods were studied, in vitro and in vivo, as an alternative treatment of fungal osteomyelitis. Implantable rods loaded with 5% fluconazole (FLU) were prepared by the injection-molding method and sterilized by gamma-irradiation at a dose of 25 kGy. Loading efficiency, physical chemistry (high performance liquid chromatography, X-ray diffraction, gel permeation chromatography), and in vitro and in vivo release assays were performed to evaluate the novel delivery systems and the sterilization effect on implant characteristics. In spite of polymer degradation after gamma-irradiation, the loading efficiency, chemical stability, and crystallographic structure of FLU were not affected. In vivo studies were carried out in femoral bone marrow of rabbits. Approximately 85 and 80% of the total dose were released within 12 and 4 weeks from PLA and L-PLA rods, respectively. This showed a faster release rate of FLU in vivo than in vitro, showing almost zero-order kinetics from PLA rods. PMID:16514603

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

    NASA Astrophysics Data System (ADS)

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

    2007-07-01

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

  11. A mini-review on novel intraperiodontal pocket drug delivery materials for the treatment of periodontal diseases.

    PubMed

    Hau, H; Rohanizadeh, R; Ghadiri, M; Chrzanowski, W

    2014-06-01

    Periodontal disease is defined as chronic inflammatory condition characterized by the destruction of the periodontal tissues causing loss of connective tissue attachment, loss of alveolar bone, and the formation of pathological pockets around the diseased teeth. The use of systemic antibiotics has been advocated for its treatment, but concerns emerged with respect to adverse drug reactions and its contribution to bacterial resistance. Thus local drug delivery devices have been developed that aim to deliver a high concentration of antimicrobial drugs directly to the affected site, while minimizing drug's systemic exposure. A burst release of antimicrobial agent from carrier, resulting in a short and inadequate exposure of bacteria residing in periodontal pocket to the agent, remains the main challenge of current local delivery systems for the treatment of periodontal disease. This review aims to investigate and compare different local antimicrobial delivery systems with regard to the treatment of periodontal disease. PMID:25786883

  12. Assessing the quality of proton PBS treatment delivery using machine log files: comprehensive analysis of clinical treatments delivered at PSI Gantry 2.

    PubMed

    Scandurra, D; Albertini, F; van der Meer, R; Meier, G; Weber, D C; Bolsi, A; Lomax, A

    2016-02-01

    Pencil beam scanning (PBS) proton therapy requires the delivery of many thousand proton beams, each modulated for position, energy and monitor units, to provide a highly conformal patient treatment. The quality of the treatment is dependent on the delivery accuracy of each beam and at each fraction. In this work we describe the use of treatment log files, which are a record of the machine parameters for a given field delivery on a given fraction, to investigate the integrity of treatment delivery compared to the nominal planned dose. The dosimetry-relevant log file parameters are used to reconstruct the 3D dose distribution on the patient anatomy, using a TPS-independent dose calculation system. The analysis was performed for patients treated at Paul Scherrer Institute on Gantry 2, both for individual fields and per series (or plan), and delivery quality was assessed by determining the percentage of voxels in the log file dose distribution within  +/-  1% of the nominal dose. It was seen that, for all series delivered, the mean pass rate is 96.4%. Furthermore, this work establishes a correlation between the delivery quality of a field and the beam position accuracy. This correlation is evident for all delivered fields regardless of individual patient or plan characteristics. We have also detailed further usefulness of log file analysis within our clinical workflow. In summary, we have highlighted that the integrity of PBS treatment delivery is dependent on daily machine performance and is specifically highly correlated with the accuracy of beam position. We believe this information will be useful for driving machine performance improvements in the PBS field. PMID:26767316

  13. Assessing the quality of proton PBS treatment delivery using machine log files: comprehensive analysis of clinical treatments delivered at PSI Gantry 2

    NASA Astrophysics Data System (ADS)

    Scandurra, D.; Albertini, F.; van der Meer, R.; Meier, G.; Weber, D. C.; Bolsi, A.; Lomax, A.

    2016-02-01

    Pencil beam scanning (PBS) proton therapy requires the delivery of many thousand proton beams, each modulated for position, energy and monitor units, to provide a highly conformal patient treatment. The quality of the treatment is dependent on the delivery accuracy of each beam and at each fraction. In this work we describe the use of treatment log files, which are a record of the machine parameters for a given field delivery on a given fraction, to investigate the integrity of treatment delivery compared to the nominal planned dose. The dosimetry-relevant log file parameters are used to reconstruct the 3D dose distribution on the patient anatomy, using a TPS-independent dose calculation system. The analysis was performed for patients treated at Paul Scherrer Institute on Gantry 2, both for individual fields and per series (or plan), and delivery quality was assessed by determining the percentage of voxels in the log file dose distribution within  +/-  1% of the nominal dose. It was seen that, for all series delivered, the mean pass rate is 96.4%. Furthermore, this work establishes a correlation between the delivery quality of a field and the beam position accuracy. This correlation is evident for all delivered fields regardless of individual patient or plan characteristics. We have also detailed further usefulness of log file analysis within our clinical workflow. In summary, we have highlighted that the integrity of PBS treatment delivery is dependent on daily machine performance and is specifically highly correlated with the accuracy of beam position. We believe this information will be useful for driving machine performance improvements in the PBS field.

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

    PubMed Central

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

    2014-01-01

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

  15. Nano-structures mediated co-delivery of therapeutic agents for glioblastoma treatment: A review.

    PubMed

    Mujokoro, Basil; Adabi, Mohsen; Sadroddiny, Esmaeil; Adabi, Mahdi; Khosravani, Masood

    2016-12-01

    Glioblastoma is a malignant brain tumor and leads to death in most patients. Chemotherapy is a common method for brain cancer in clinics. However, the recent advancements in the chemotherapy of brain tumors have not been efficient enough. With the advancement of nanotechnology, the used drugs can enhance chemotherapy efficiency and increase the access to brain cancers. Combination of therapeutic agents has been recently attracted great attention for glioblastoma chemotherapy. One of the early benefits of combination therapies is the high potential to provide synergistic effects and decrease adverse side effects associated with high doses of single anticancer drugs. Therefore, brain tumor treatments with combination drugs can be considered as a crucial approach for avoiding tumor growth. This review investigates current progress in nano-mediated co-delivery of therapeutic agents with focus on glioblastoma chemotherapy prognosis. PMID:27612807

  16. Experience in the 532-nm green laser treatment of cutaneous angiodysplasias using an automatic delivery system

    NASA Astrophysics Data System (ADS)

    Mordon, Serge R.; Suchet-Lopez, Marie A.; Rotteleur, Guy; Brunetaud, Jean Marc

    1992-06-01

    Cutaneous angiodysplasias are currently treated by Argon, CW-Dye or Pulsed Dye Lasers. Green light at 532 nm is highly specific for hemoglobin-laden vessels. Therefore, this wavelength was evaluated on different cutaneous angiodysplasias. One hundred thirty-five (135) patients with either port wine stains (94) or facial telangiectasia (41) were treated with a 532 nm laser coupled to an automatic delivery system. Treatments were performed using the minimal blanching technique. The average fluence was 17 J/cm-2 for port wine stains and 15 J/cm-2 for facial telangiectasia. Pathologic scars were not reported for any patient. Sixty percent (60%) of the patients with port wine stains achieved good or excellent results after a 12-month period of observations. Ninety percent (90%) of the patients with facial telangiectasia achieved good or excellent results after a 12-month period of observation.

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

    SciTech Connect

    Dhanesar, Sandeep; Darko, Johnson; Joshi, Chandra P.; Kerr, Andrew; John Schreiner, L.

    2013-08-15

    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

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

    NASA Astrophysics Data System (ADS)

    Dhanesar, Sandeep Kaur

    Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen's University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system

  19. Delivery strategies for treatment of age-related ocular diseases: From a biological understanding to biomaterial solutions.

    PubMed

    Delplace, Vianney; Payne, Samantha; Shoichet, Molly

    2015-12-10

    Age-related ocular diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, result in life-long functional deficits and enormous global health care costs. As the worldwide population ages, vision loss has become a major concern for both economic and human health reasons. Due to recent research into biomaterials and nanotechnology major advances have been gained in the field of ocular delivery. This review provides a summary and discussion of the most recent strategies employed for the delivery of both drugs and cells to the eye to treat a variety of age-related diseases. It emphasizes the current challenges and limitations to ocular delivery and how the use of innovative materials can overcome these issues and ultimately provide treatment for age-related degeneration and regeneration of lost tissues. This review also provides critical considerations and an outlook for future studies in the field of ophthalmic delivery. PMID:26435454

  20. Dual-responsive polymer coated superparamagnetic nanoparticle for targeted drug delivery and hyperthermia treatment.

    PubMed

    Patra, Santanu; Roy, Ekta; Karfa, Paramita; Kumar, Sunil; Madhuri, Rashmi; Sharma, Prashant K

    2015-05-01

    In this work, we have prepared water-soluble superparamgnetic iron oxide nanoparticles (SPIONs) coated with a dual responsive polymer for targeted delivery of anticancer hydrophobic drug (curcumin) and hyperthermia treatment. Herein, superparamagnetic mixed spinel (MnFe2O4) was used as a core material (15-20 nm) and modified with carboxymethyl cellulose (water-soluble component), folic acid (tagging agent), and dual responsive polymer (poly-N isopropylacrylamide-co-poly glutamic acid) by microwave radiation. Lower critical solution temperature (LCST) of the thermoresponsive copolymer was observed to be around 40 °C, which is appropriate for drug delivery. The polymer-SPIONs show high drug loading capacity (89%) with efficient and fast drug release at the desired pH (5.5) and temperature (40 °C) conditions. Along with this, the SPIONs show a very fast increase in temperature (45 °C in 2 min) when interacting with an external magnetic field, which is an effective and appropriate temperature for the localized hyperthermia treatment of cancer cells. The cytocompatibility of the curcumin loaded SPIONs was studied by the methyl thiazol tetrazolium bromide (MTT) assay, and cells were imaged by fluorescence microscopy. To explore the targeting behavior of curcumin loaded SPIONs, a simple magnetic capturing system (simulating a blood vessel) was constructed and it was found that ∼99% of the nanoparticle accumulated around the magnet in 2 min by traveling a distance of 30 cm. Along with this, to explore an entirely different aspect of the responsive polymer, its antibacterial activity toward an E. coli strain was also studied. It was found that responsive polymer is not harmful for normal or cancer cells but shows a good antibacterial property. PMID:25893447

  1. Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis.

    PubMed

    Bessar, Hagar; Venditti, Iole; Benassi, Luisa; Vaschieri, Cristina; Azzoni, Paola; Pellacani, Giovanni; Magnoni, Cristina; Botti, Elisabetta; Casagrande, Viviana; Federici, Massimo; Costanzo, Antonio; Fontana, Laura; Testa, Giovanna; Mostafa, Fawzia Farag; Ibrahim, Samia Ali; Russo, Maria Vittoria; Fratoddi, Ilaria

    2016-05-01

    Gold nanoparticles (AuNPs) represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. Even if systemic, methotrexate still plays an important role in psoriasis treatment: its topical use shows insufficient percutaneus penetration owing to limited passive diffusion, high molecular weight and dissociation at physiological pH. The aim of our study was to design a new drug delivery nanocarrier for Methotrexate and to improve its solubility, stability and biodistribution. AuNPs were on purpose prepared with a hydrophilic stabilizing layer, in order to improve the colloidal stability in water. Water-soluble gold nanoparticles functionalized by sodium 3-mercapto-1-propansulfonate (Au-3MPS) were prepared and loaded with methotrexate (MTX). The loading efficiency of MTX on Au-3MPS was assessed in the range 70-80%, with a fast release (80% in one hour). The release was studied up to 24h reaching the value of 95%. The Au-3MPS@MTX conjugate was fully characterized by spectroscopic techniques (UV-vis, FTIR) and DLS. Preliminary toxicity tests in the presence of keratinocytes monolayers allowed to assess that the used Au-3MPS are not toxic. The conjugate was then topically used on C57BL/6 mouse normal skin in order to trace the absorption behavior. STEM images clearly revealed the distribution of gold nanoparticles inside the cells. In vitro studies showed that Methotrexate conjugated with Au-3MPS is much more efficient than Methotrexate alone. Moreover, DL50, based on MTT analysis, is 20 folds reduced at 48 h, by the presence of nanoparticles conjugation. UV-vis spectra for in vivo tracing of the conjugate on bare mouse skin after 24h of application, show increased delivery of Methotrexate in the epidermis and dermis using Au-3MPS@MTX conjugate, compared to MTX alone. Moreover we observed absence of the Au-3MPS in the dermis and in the epidermis, suggesting that

  2. Virosome, a hybrid vehicle for efficient and safe drug delivery and its emerging application in cancer treatment.

    PubMed

    Liu, Hanqing; Tu, Zhigang; Feng, Fan; Shi, Haifeng; Chen, Keping; Xu, Ximing

    2015-06-01

    A virosome is an innovative hybrid drug delivery system with advantages of both viral and non-viral vectors. Studies have shown that a virosome can carry various biologically active molecules, such as nucleic acids, peptides, proteins and small organic molecules. Targeted drug delivery using virosome-based systems can be achieved through surface modifications of virosomes. A number of virosome-based prophylactic and therapeutic products with high safety profiles are currently available in the market. Cancer treatment is a big battlefield for virosome-based drug delivery systems. This review provides an overview of the general concept, preparation procedures, working mechanisms, preclinical studies and clinical applications of virosomes in cancer treatment. PMID:26011928

  3. Noninvasive, Targeted, and Non-Viral Ultrasound-Mediated GDNF-Plasmid Delivery for Treatment of Parkinson’s Disease

    PubMed Central

    Fan, Ching-Hsiang; Ting, Chien-Yu; Lin, Chung‐Yin; Chan, Hong-Lin; Chang, Yuan-Chih; Chen, You-Yin; Liu, Hao-Li; Yeh, Chih-Kuang

    2016-01-01

    Glial cell line-derived neurotrophic factor (GDNF) supports the growth and survival of dopaminergic neurons. CNS gene delivery currently relies on invasive intracerebral injection to transit the blood-brain barrier. Non-viral gene delivery via systematic transvascular route is an attractive alternative because it is non-invasive, but a high-yield and targeted gene-expressed method is still lacking. In this study, we propose a novel non-viral gene delivery approach to achieve targeted gene transfection. Cationic microbubbles as gene carriers were developed to allow the stable formation of a bubble-GDNF gene complex, and transcranial focused ultrasound (FUS) exposure concurrently interacting with the bubble-gene complex allowed transient gene permeation and induced local GDNF expression. We demonstrate that the focused ultrasound-triggered GDNFp-loaded cationic microbubbles platform can achieve non-viral targeted gene delivery via a noninvasive administration route, outperform intracerebral injection in terms of targeted GDNF delivery of high-titer GDNF genes, and has a neuroprotection effect in Parkinson’s disease (PD) animal models to successfully block PD syndrome progression and to restore behavioral function. This study explores the potential of using FUS and bubble-gene complexes to achieve noninvasive and targeted gene delivery for the treatment of neurodegenerative disease. PMID:26786201

  4. Development of a rectal nicotine delivery system for the treatment of ulcerative colitis.

    PubMed

    Dash, A K; Gong, Z; Miller, D W; Huai-Yan, H; Laforet, J

    1999-11-10

    The aims of this investigation were: i. to develop a rectal nicotine delivery system with bioadhesives for the treatment of ulcerative colitis and ii. to evaluate nicotine transport and cytotoxicity of the delivery system using Caco-2 cell culture systems. Rectal nicotine suppository formulations were prepared in semi-synthetic glyceride bases (Suppocire AM and AI, Gattefosse Inc.) by fusion method. The in vitro release of nicotine was carried out in modified USP dissolution apparatus 1. Differential scanning calorimetry (DSC) and powder X-ray diffraction were used to study the polymorphic changes if any in the formulations. An LC method was used for the assay of nicotine. The effect of bioadhesives (glyceryl monooleate (GMO), and Carbopol) on the nicotine flux was evaluated using Caco-2 cell permeability studies and Caco-2 cell viability was determined using the MTT toxicity assay. In vitro release studies indicated that the low melting AI base was superior to that of the AM base. Presence of GMO in the formulation enhanced the release of nicotine whereas Carbopol showed an opposite effect. The enhanced release of nicotine in the presence of GMO was found to be partly due to the melting point lowering effect of this compound. Caco-2 cell absorption studies showed that there was a decrease in the flux of nicotine in the presence of both the bioadhesives. The flux of the fluorescein marker which is used to study the integrity of the cell monolayers was found to be slightly higher only in the presence of 10% (w/w) Carbopol. Nicotine, Carbopol, and GMO do not have any cytotoxic effect on these cell monolayers within the concentration range used in the formulations. Rectal nicotine formulations containing bioadhesives were developed and characterized. Both in vitro release and cell culture studies have indicated that one can manipulate the nicotine release from these rectal delivery systems by incorporation of various bioadhesives or the use of different bases in the

  5. Nanoethosomal transdermal delivery of vardenafil for treatment of erectile dysfunction: optimization, characterization, and in vivo evaluation

    PubMed Central

    Fahmy, Usama A

    2015-01-01

    Vesicular drug delivery systems have recently gained attention as a way of improving dosing accuracy for drugs with poor transdermal permeation. The current study focuses on utilization of the natural biocompatible vesicles to formulate vardenafil nanoethosomes (VRD-NE), for the enhancement of their transdermal permeation and bioavailability. Fifteen formulations were prepared by thin-layer evaporation technique according to Box–Behnken design to optimize formulation variables. The effects of lipid composition, sonication time, and ethanol concentration on particle size and encapsulation efficiency were studied. The diffusion of vardenafil (VRD) from the prepared nanoethosomes specified by the design was carried out using automated Franz diffusion cell apparatus. The optimized formula was investigated for in vivo pharmacokinetic parameters compared with oral VRD suspension. Confocal laser scanning microscopy images were used to confirm enhanced diffusion release of VRD in rat skin. The results showed that the optimized formula produced nanoethosomes with an average size of 128 nm and an entrapment efficiency of 76.23%. VRD-NE provided a significant improvement in permeation with an enhancement ratio of 3.05-fold for a film made with optimally formulated VRD-NE compared with a film made with VRD powder. The transdermal bioavailability of VRD from the nanoethosome film was approximately twofold higher than the oral bioavailability from an aqueous suspension. VRD-NE thus provide a promising transdermal drug delivery system. As a result, management of impotence for a longer duration could be achieved with a reduced dosage rate that improves patient tolerability and compliance for the treatment of erectile dysfunction. PMID:26604700

  6. Nanoethosomal transdermal delivery of vardenafil for treatment of erectile dysfunction: optimization, characterization, and in vivo evaluation.

    PubMed

    Fahmy, Usama A

    2015-01-01

    Vesicular drug delivery systems have recently gained attention as a way of improving dosing accuracy for drugs with poor transdermal permeation. The current study focuses on utilization of the natural biocompatible vesicles to formulate vardenafil nanoethosomes (VRD-NE), for the enhancement of their transdermal permeation and bioavailability. Fifteen formulations were prepared by thin-layer evaporation technique according to Box-Behnken design to optimize formulation variables. The effects of lipid composition, sonication time, and ethanol concentration on particle size and encapsulation efficiency were studied. The diffusion of vardenafil (VRD) from the prepared nanoethosomes specified by the design was carried out using automated Franz diffusion cell apparatus. The optimized formula was investigated for in vivo pharmacokinetic parameters compared with oral VRD suspension. Confocal laser scanning microscopy images were used to confirm enhanced diffusion release of VRD in rat skin. The results showed that the optimized formula produced nanoethosomes with an average size of 128 nm and an entrapment efficiency of 76.23%. VRD-NE provided a significant improvement in permeation with an enhancement ratio of 3.05-fold for a film made with optimally formulated VRD-NE compared with a film made with VRD powder. The transdermal bioavailability of VRD from the nanoethosome film was approximately twofold higher than the oral bioavailability from an aqueous suspension. VRD-NE thus provide a promising transdermal drug delivery system. As a result, management of impotence for a longer duration could be achieved with a reduced dosage rate that improves patient tolerability and compliance for the treatment of erectile dysfunction. PMID:26604700

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

    PubMed

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

    2008-01-01

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

  8. Treatment of blood flow abnormality using mucosal delivery of nitric oxide.

    PubMed

    Lee, Chi H

    2011-06-01

    This review focuses on clinical application of intravaginal formulations containing nitric oxide (NO). Poly(D,L-lactic acid-co-glycolic acid)-based microparticles or nanoparticles encapsulated with nitric oxide prodrugs, such as diethylenetriamine diazeniumdiolate and S-nitrosoglutathione, have been developed for the treatment of blood flow abnormality in various diseases including diabetes. Advanced nanotechnology allows for production of novel formulations with the capability of long-term protection, preserving the integrity of the NO donors, and delivering NO in a controlled and sustained release manner at the mucosal sites. The gene expressions of MAPK and PKC in the vaginal mucosa upon exposure to microparticles were evaluated for the mechanistic study involved with blood flow changes. The blood flow changes and protein expression of the vaginal mucosa upon exposure to intravaginal formulations containing NO donors supported that NO therapy would be suitable for the treatment of blood flow abnormality. This review subsequently would help to establish a scientific foundation for clinical trials of intravaginal NO delivery systems in humans. PMID:25788240

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

    PubMed

    Hashizume, Rintaro; Gupta, Nalin

    2010-04-01

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

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

    PubMed

    Fiehn, C

    2010-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  12. Accurate Treatment of Large Supramolecular Complexes by Double-Hybrid Density Functionals Coupled with Nonlocal van der Waals Corrections.

    PubMed

    Calbo, Joaquín; Ortí, Enrique; Sancho-García, Juan C; Aragó, Juan

    2015-03-10

    In this work, we present a thorough assessment of the performance of some representative double-hybrid density functionals (revPBE0-DH-NL and B2PLYP-NL) as well as their parent hybrid and GGA counterparts, in combination with the most modern version of the nonlocal (NL) van der Waals correction to describe very large weakly interacting molecular systems dominated by noncovalent interactions. Prior to the assessment, an accurate and homogeneous set of reference interaction energies was computed for the supramolecular complexes constituting the L7 and S12L data sets by using the novel, precise, and efficient DLPNO-CCSD(T) method at the complete basis set limit (CBS). The correction of the basis set superposition error and the inclusion of the deformation energies (for the S12L set) have been crucial for obtaining precise DLPNO-CCSD(T)/CBS interaction energies. Among the density functionals evaluated, the double-hybrid revPBE0-DH-NL and B2PLYP-NL with the three-body dispersion correction provide remarkably accurate association energies very close to the chemical accuracy. Overall, the NL van der Waals approach combined with proper density functionals can be seen as an accurate and affordable computational tool for the modeling of large weakly bonded supramolecular systems. PMID:26579747

  13. Innovative delivery systems for migraine: the clinical utility of a transdermal patch for the acute treatment of migraine.

    PubMed

    Rapoport, Alan M; Freitag, Fred; Pearlman, Starr H

    2010-11-01

    Migraine is a disabling, painful primary headache disorder that is associated with various combinations of neurological, gastrointestinal, autonomic and pain symptoms. Gastrointestinal disturbances associated with migraine, including nausea and vomiting, affect a majority of migraineurs and often result in a delay in taking or avoidance of pharmacological intervention. Gastric stasis and vomiting may lead to delayed or inconsistent absorption of orally administered medications. Many migraineurs awake early in the morning with their attack progressing and already associated with nausea and vomiting. As a result, there is a need for a novel, non-invasive, non-oral delivery system for fast and effective acute treatment of migraine. There are two non-oral delivery systems currently available in the US for the acute treatment of migraine: three nasal sprays and two injectable formulations. Although nasal sprays depend partially on nasal mucosal absorption, a significant amount of drug is swallowed, transits the stomach and is absorbed in the small intestine, which is not as rapid or effective a route of delivery for those migraineurs with gastric stasis. Sumatriptan is rapidly absorbed by subcutaneous injection with or without a needle, but the invasiveness and discomfort of the delivery, the high incidence of adverse events and the high recurrence rate all limit its use for many patients. Iontophoretic delivery of medication is a non-invasive transdermal approach that uses small amounts of electrical current to promote rapid movement of the ionized drug through the skin and into the systemic circulation. This delivery bypasses hepatic first-pass metabolism and also avoids gastric transit delay and slowing of small intestinal absorption associated with gastrointestinal stasis in migraineurs. Two pharmacokinetic studies have demonstrated that iontophoretic transdermal delivery of sumatriptan results in rapid and consistent achievement of therapeutic plasma concentrations

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

    PubMed Central

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

    2012-01-01

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

  15. Current nanotechnological strategies for effective delivery of bioactive drug molecules in the treatment of tuberculosis.

    PubMed

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

    2014-01-01

    Tuberculosis (TB) has gone from being a forgotten disease to a modern and recrudescent pathology from past decades. Some clinical problems and challenges associated with conventional TB chemotherapy include poor patient compliance, longer duration of chemotherapy, lesser cell permeability, primary drug resistance, difficulty in maintaining higher drug concentrations at the infected site, and degradation of the drug before reaching the target site. Thus, newer drug delivery approaches involving micrometric or nanometric carriers are needed. These delivery systems should provide advantages over conventional systems by producing optimum effectiveness to the target site, enhanced therapeutic efficacy, uniform distribution of the drug throughout the target site, increased bioavailability and sustainability of the drug, fewer side effects, and increased patient compliance. This article reviews recent updates and fabrication of drug delivery approaches for tuberculosis chemotherapy involving vesicular drug delivery systems (liposomes, niosomes, solid lipid nanoparticles), particulate drug delivery systems (nanoparticles, microparticles, dendrimers), supramolecular drug delivery systems (polymeric micelles), specialized drug delivery systems (nanosuspensions, nanoemulsions, microemulsions, dry powders), complex conjugate drug delivery systems (ISCOMs, cyclodextrin inclusion complexes), and other carrier-based drug delivery systems in order to improve patient outcomes. PMID:24579767

  16. Local delivery system of doxycycline hyclate based on ε-caprolactone copolymers for periodontitis treatment.

    PubMed

    Kopytynska-Kasperczyk, Anna; Dobrzynski, Piotr; Pastusiak, Małgorzata; Jarzabek, Bozena; Prochwicz, Wojciech

    2015-08-01

    The aim of the study was to evaluate kinetics of doxycycline hyclate release from polymeric bioresorbable implants and to examine suitability of this system for local treatment of periodontitis. Selected trimethylene carbonate/ϵ-caprolactone (TMC/CL) and glycolide/caprolactone (GL/CL) copolymers were synthesized and used as carriers in the form of small elastic rings with 5 wt% and 10 wt% doxycycline hyclate content, or in the form of flakes obtained through electro-spinning technique. The release of the drug under in vitro conditions has been tested. The study has shown that equimolar TMC/CL copolymer loaded with 10 wt% of doxycycline hyclate appears to be the most suitable copolymer for assumed system. The drug release proceeds mainly by diffusion of medium into the polymeric matrix and then the drug is washed out. Daily validation of doxycycline doses released by the system should ensure accurate course of the therapy. PMID:26143233

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

    PubMed Central

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

    2014-01-01

    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

  18. Characterization of corrosion scale formed on stainless steel delivery pipe for reclaimed water treatment.

    PubMed

    Cui, Yong; Liu, Shuming; Smith, Kate; Yu, Kanghua; Hu, Hongying; Jiang, Wei; Li, Yuhong

    2016-01-01

    To reveal corrosion behavior of stainless steel delivery pipe used in reclaimed water treatment, this research focused on the morphological, mineralogical and chemical characteristics of stainless steel corrosion scale and corroded passive film. Corrosion scale and coupon samples were taken from a type 304 pipe delivering reclaimed water to a clear well in service for more than 12 years. Stainless steel corrosion scales and four representative pipe coupons were investigated using mineralogy and material science research methods. The results showed corrosion scale was predominantly composed of goethite, lepidocrocite, hematite, magnetite, ferrous oxide, siderite, chrome green and chromite, the same as that of corroded pipe coupons. Hence, corrosion scale can be identified as podiform chromite deposit. The loss of chromium in passive film is a critical phenomenon when stainless steel passive film is damaged by localized corrosion. This may provide key insights toward improving a better comprehension of the formation of stainless steel corrosion scale and the process of localized corrosion. The localized corrosion behavior of stainless steel is directly connected with reclaimed water quality parameters such as residual chlorine, DO, Cl(-) and SO4(2-). In particular, when a certain amount of residual chlorine in reclaimed water is present as an oxidant, ferric iron is the main chemical state of iron minerals. PMID:26605686

  19. Nanodroplet-Vaporization-Assisted Sonoporation for Highly Effective Delivery of Photothermal Treatment

    PubMed Central

    Liu, Wei-Wen; Liu, Shu-Wei; Liou, Yu-Ren; Wu, Yu-Hsun; Yang, Ya-Chuen; Wang, Churng-Ren Chris; Li, Pai-Chi

    2016-01-01

    Sonoporation refers to the use of ultrasound and acoustic cavitation to temporarily enhance the permeability of cellular membranes so as to enhance the delivery efficiency of therapeutic agents into cells. Microbubble-based ultrasound contrast agents are often used to facilitate these cavitation effects. This study used nanodroplets to significantly enhance the effectiveness of sonoporation relative to using conventional microbubbles. Significant enhancements were demonstrated both in vitro and in vivo by using gold nanorods encapsulated in nanodroplets for implementing plasmonic photothermal therapy. Combined excitation by ultrasound and laser radiation is used to trigger the gold nanodroplets to induce a liquid-to-gas phase change, which induces cavitation effects that are three-to-fivefold stronger than when using conventional microbubbles. Enhanced cavitation also leads to significant enhancement of the sonoporation effects. Our in vivo results show that nanodroplet-vaporization-assisted sonoporation can increase the treatment temperature by more than 10 °C above that achieved by microbubble-based sonoporation. PMID:27094209

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

    PubMed

    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

    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. PMID:24824141

  1. A new era of cancer treatment: carbon nanotubes as drug delivery tools

    PubMed Central

    Madani, Seyed Yazdan; Naderi, Naghmeh; Dissanayake, Oshani; Tan, Aaron; Seifalian, Alexander M

    2011-01-01

    Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology. PMID:22162655

  2. A Novel Vehicle for Enhanced Drug Delivery Across the Human Nail for the Treatment of Onychomycosis.

    PubMed

    Turner, Rob; Weaver, Sean; Caserta, Francesco; Brown, Marc B

    2016-01-01

    The aim of this study was to use in vitro nail models to investigate the potential of a novel base formulation (Recura) containing either fluconazole or miconazole for the treatment of onychomycosis in comparison to two commercial comparators (Jublia and a Penlac generic). Initially, a modified Franz cell was used, where sections of human nail served as the barrier through which drug penetrated into an agar-filled chamber infected with dermatophytes. A second study was performed using a novel infected nail model where dermatophytes grew into human nail and adenosine triphosphate levels were used as biological marker for antimicrobial activity. The novel enhancing system Recura increased the permeation of both existing drugs through human nail sections mounted in a modified Franz cell. Furthermore, the infected nail model also confirmed that the system also enhanced the permeation through infected nail resulting in a decrease in adenosine triphosphate levels superior (P ≤ 0.05) to Penlac generic and equivalent (P > 0.05) to the commercial comparator Jublia. This study demonstrated that with the use of a novel permeation-enhancing formulation base, Recura enhances delivery of miconazole and fluconazole when applied ungually such that the efficacy was equivalent or superior to commercial comparators. Such a topically applied system has the possibility of overcoming the systemic side effects of antifungals when taken orally. PMID:27125057

  3. Nanodroplet-Vaporization-Assisted Sonoporation for Highly Effective Delivery of Photothermal Treatment

    NASA Astrophysics Data System (ADS)

    Liu, Wei-Wen; Liu, Shu-Wei; Liou, Yu-Ren; Wu, Yu-Hsun; Yang, Ya-Chuen; Wang, Churng-Ren Chris; Li, Pai-Chi

    2016-04-01

    Sonoporation refers to the use of ultrasound and acoustic cavitation to temporarily enhance the permeability of cellular membranes so as to enhance the delivery efficiency of therapeutic agents into cells. Microbubble-based ultrasound contrast agents are often used to facilitate these cavitation effects. This study used nanodroplets to significantly enhance the effectiveness of sonoporation relative to using conventional microbubbles. Significant enhancements were demonstrated both in vitro and in vivo by using gold nanorods encapsulated in nanodroplets for implementing plasmonic photothermal therapy. Combined excitation by ultrasound and laser radiation is used to trigger the gold nanodroplets to induce a liquid-to-gas phase change, which induces cavitation effects that are three-to-fivefold stronger than when using conventional microbubbles. Enhanced cavitation also leads to significant enhancement of the sonoporation effects. Our in vivo results show that nanodroplet-vaporization-assisted sonoporation can increase the treatment temperature by more than 10 °C above that achieved by microbubble-based sonoporation.

  4. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases.

    PubMed

    Bhalaria, M K; Naik, Sachin; Misra, A N

    2009-05-01

    Aim of this work was to prepare and characterize fluconazole (FLZ) encapsulated ethosomes, incorporate it in suitable dermatological base, and asses its comparative clinical efficacy in the treatment of Candidiasis patients against liposomal gel, marketed product and hydroethanolic solution of the drug. Drug encapsulated ethosomes and liposomes were prepared and optimized by "Hot" method technique and lipid film hydration technique. Vesicular carriers were characterized for % entrapment efficiency, particle size and shape, in vitro drug diffusion study, mean % reduction in dimension of Candidiasis lesion and stability study by using suitable analytical technique. Vesicle size and drug entrapment efficiency of the optimized ethosomes and liposomes were found to be 144 +/- 6.8 nm and 82.68% and 216 +/- 9.2 nm and 68.22% respectively. Microscopic examinations suggest ethosomes to be multilamellar spherical vesicles with a smooth surface. The differential scanning calorimetry results suggest high fluidity of the ethosomes than liposomes. In vitro drug diffusion studies demonstrated that % drug diffused from ethosomes was nearly twice than liposomes and three times higher than the hydroethanolic solution across rat skin. From the clinical evaluation, the developed novel delivery system demonstrated enhanced antifungal activity compared to liposomal formulation, marketed formulation and hydroethanolic solution of the drug. PMID:19579803

  5. Polymeric Micelle-Mediated Delivery of DNA-Targeting Organometallic Complexes for Resistant Ovarian Cancer Treatment.

    PubMed

    Duan, Xiaopin; Liu, Demin; Chan, Christina; Lin, Wenbin

    2015-08-26

    Three half-sandwich iridium and ruthenium organometallic complexes with high cytotoxicity are synthesized, and their anticancer mechanisms are elucidated. The organometallic complexes can interact with DNA through coordination or intercalation, thereby inducing apoptosis and inhibiting proliferation of resistant cancer cells. The organometallic complexes are then incorporated into polymeric micelles through the polymer-metal coordination between poly(ethylene glycol)-b-poly(glutamic acid) [PEG-b-P(Glu)] and organometallic complexes to further enhance their anticancer effects as a result of the enhanced permeability and retention effect. The micelles with particle sizes of ≈60 nm are more efficiently internalized by cancer cells than the corresponding complexes, and selectively dissociate and release organometallic anticancer agents within late endosomes and lysosomes, thereby enhancing drug delivery to the nuclei of cancer cells and facilitating their interactions with DNA. Thus, the micelles display higher antitumor activity than the organometallic complexes alone with a lack of the systemic toxicity in a mouse xenograft model of cisplatin-resistant human ovarian cancer. These results suggest that the polymeric micelles carrying anticancer organometallic complexes provide a promising platform for the treatment of resistant ovarian cancer and other hard-to-treat solid tumors. PMID:25963931

  6. A novel four-dimensional radiotherapy method for lung cancer: imaging, treatment planning and delivery

    NASA Astrophysics Data System (ADS)

    Alasti, H.; Cho, Y. B.; Vandermeer, A. D.; Abbas, A.; Norrlinger, B.; Shubbar, S.; Bezjak, A.

    2006-06-01

    We present treatment planning methods based on four-dimensional computed tomography (4D-CT) to incorporate tumour motion using (1) a static field and (2) a dynamic field. Static 4D fields are determined to include the target in all breathing phases, whereas dynamic 4D fields are determined to follow the shape of the tumour assessed from 4D-CT images with a dynamic weighting factor. The weighting factor selection depends on the reliability of patient breathing and limitations of the delivery system. The static 4D method is compared with our standard protocol for gross tumour volume (GTV) coverage, mean lung dose and V20. It was found that the GTV delineated on helical CT without incorporating breathing motion does not adequately represent the target compared to the GTV delineated from 4D-CT. Dosimetric analysis indicates that the static 4D-CT based technique results in a reduction of the mean lung dose compared with the standard protocol. Measurements on a moving phantom and simulations indicated that 4D radiotherapy (4D-RT) synchronized with respiration-induced motion further reduces mean lung dose and V20, and may allow safe application of dose escalation and CRT/IMRT. The motions of the chest cavity, tumour and thoracic structures of 24 lung cancer patients are also analysed.

  7. Predictive Factors for Delivery within 7 Days after Successful 48-Hour Treatment of Threatened Preterm Labor

    PubMed Central

    Roos, Carolien; Schuit, Ewoud; Scheepers, Hubertina C. J.; Bloemenkamp, Kitty W. M.; Bolte, Antoinette C.; Duvekot, Hans J. J.; van Eyck, Jim; Kok, Joke H.; Kwee, Anneke; Merién, Ashley E. R.; Opmeer, Brent C.; Oudijk, Martijn A.; van Pampus, Mariëlle G.; Papatsonis, Dimitri N. M.; Porath, Martina M.; Sollie, Krystyna M.; Spaanderman, Marc E. A.; Vijgen, Sylvia M. C.; Willekes, Christine; Lotgering, Fred K.; van der Post, Joris A. M.; Mol, Ben Willem J.

    2015-01-01

    Objective The aim of this study was to assess which characteristics and results of vaginal examination are predictive for delivery within 7 days, in women with threatened preterm labor after initial treatment. Study Design A secondary analysis of a randomized controlled trial on maintenance nifedipine includes women who remained undelivered after threatened preterm labor for 48 hours. We developed one model for women with premature prelabor rupture of membranes (PPROM) and one without PPROM. The predictors were identified by backward selection. We assessed calibration and discrimination and used bootstrapping techniques to correct for potential overfitting. Results For women with PPROM (model 1), nulliparity, history of preterm birth, and vaginal bleeding were included in the multivariable analysis. For women without PPROM (model 2), maternal age, vaginal bleeding, cervical length, and fetal fibronectin (fFN) status were in the multivariable analysis. Discriminative capability was moderate to good (c-statistic 0.68; 95% confidence interval [CI] 0.60–0.77 for model 1 and 0.89; 95% CI, 0.84–0.93 for model 2). Conclusion PPROM and vaginal bleeding in the current pregnancy are relevant predictive factors in all women, as are maternal age, cervical length, and fFN in women without PPROM and nulliparity, history of preterm birth in women with PPROM. PMID:26495173

  8. Monocytic delivery of therapeutic oxygen bubbles for dual-modality treatment of tumor hypoxia.

    PubMed

    Huang, Wen-Chia; Shen, Ming-Yin; Chen, Hsin-Hung; Lin, Sung-Chyr; Chiang, Wen-Hsuan; Wu, Pei-Hsuan; Chang, Chien-Wen; Chiang, Chi-Shiun; Chiu, Hsin-Cheng

    2015-12-28

    Photodynamic therapy (PDT) is a powerful technique photochemically tailored for activating apoptosis of malignant cells. Although PDT has shown promise in several clinical applications, malignant cells in hypoxic regions are often resistant to PDT due to the transport limitation of therapeutics and the oxygen-dependent nature of PDT. Herein, we present an innovative strategy for overcoming the limits of PDT in tumor hypoxia using bone marrow-derived monocytes as cellular vehicles for co-transport of oxygen and red light activatable photosensitizer, chlorin e6 (Ce6). Superparamagnetic iron oxide nanoparticle/Ce6/oxygen-loaded polymer bubbles were prepared and internalized into tumortropic monocytes. These functional bubbles were found harmless to cellular hosts without external triggers. Nevertheless, the therapeutic monocytes exhibited a superior performance in inhibiting tumor growth on Tramp-C1 tumor-bearing mice (C57BL/6J) upon the treatments of tumors with high frequency magnetic field and red light laser (660 nm). Histological examinations of the tumor sections confirmed the successful cellular transport of therapeutic payloads to tumor hypoxia and the pronounced antitumor effect elicited by combined hyperthermia/photodynamic therapy along with the additional oxygen supply. This work demonstrates that this oxygen/therapeutic co-delivery via tumortropic monocytes toward tumor hypoxia is promising for improving PDT efficacy. PMID:26374945

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

    NASA Astrophysics Data System (ADS)

    Brann, Tyler

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

  10. Development of nanoantibiotic delivery system using cockle shell-derived aragonite nanoparticles for treatment of osteomyelitis

    PubMed Central

    Saidykhan, Lamin; Abu Bakar, Md Zuki Bin; Rukayadi, Yaya; Kura, Aminu Umar; Latifah, Saiful Yazan

    2016-01-01

    A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the most effective therapeutic approach for the treatment of osteomyelitis. However, the design of a biodegradable LADS with high therapeutic efficacy is too costly and demanding. In this research, a low-cost, facile method was used to design vancomycin-loaded aragonite nanoparticles (VANPs) with the aim of understanding its potency in developing a nanoantibiotic bone implant for the treatment of osteomyelitis. The aragonite nanoparticles (ANPs) were synthesized from cockle shells by a hydrothermal approach using a zwitterionic surfactant. VANPs were prepared using antibiotic ratios of several nanoparticles, and the formulation (1:4) with the highest drug-loading efficiency (54.05%) was used for physicochemical, in vitro drug release, and biological evaluation. Physiochemical characterization of VANP was performed by using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and Zetasizer. No significant differences were observed between VANP and ANP in terms of size and morphology as both samples were cubic shaped with sizes of approximately 35 nm. The Fourier transform infrared spectroscopy of VANP indicated a weak noncovalent interaction between ANP and vancomycin, while the zeta potential values were slightly increased from −19.4±3.3 to −21.2±5.7 mV after vancomycin loading. VANP displayed 120 hours (5 days) release profile of vancomycin that exhibited high antibacterial effect against methicillin-resistant Staphylococcus aureus ATCC 29213. The cell proliferation assay showed 80% cell viability of human fetal osteoblast cell line 1.19 treated with the highest concentration of VANP (250 µg/mL), indicating good biocompatibility of VANP. In summary, VANP is a potential formulation for the development of an LADS against osteomyelitis with optimal antibacterial efficacy, good bone resorbability, and biocompatibility. PMID

  11. Development of nanoantibiotic delivery system using cockle shell-derived aragonite nanoparticles for treatment of osteomyelitis.

    PubMed

    Saidykhan, Lamin; Abu Bakar, Md Zuki Bin; Rukayadi, Yaya; Kura, Aminu Umar; Latifah, Saiful Yazan

    2016-01-01

    A local antibiotic delivery system (LADS) with biodegradable drug vehicles is recognized as the most effective therapeutic approach for the treatment of osteomyelitis. However, the design of a biodegradable LADS with high therapeutic efficacy is too costly and demanding. In this research, a low-cost, facile method was used to design vancomycin-loaded aragonite nanoparticles (VANPs) with the aim of understanding its potency in developing a nanoantibiotic bone implant for the treatment of osteomyelitis. The aragonite nanoparticles (ANPs) were synthesized from cockle shells by a hydrothermal approach using a zwitterionic surfactant. VANPs were prepared using antibiotic ratios of several nanoparticles, and the formulation (1:4) with the highest drug-loading efficiency (54.05%) was used for physicochemical, in vitro drug release, and biological evaluation. Physiochemical characterization of VANP was performed by using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and Zetasizer. No significant differences were observed between VANP and ANP in terms of size and morphology as both samples were cubic shaped with sizes of approximately 35 nm. The Fourier transform infrared spectroscopy of VANP indicated a weak noncovalent interaction between ANP and vancomycin, while the zeta potential values were slightly increased from -19.4±3.3 to -21.2±5.7 mV after vancomycin loading. VANP displayed 120 hours (5 days) release profile of vancomycin that exhibited high antibacterial effect against methicillin-resistant Staphylococcus aureus ATCC 29213. The cell proliferation assay showed 80% cell viability of human fetal osteoblast cell line 1.19 treated with the highest concentration of VANP (250 µg/mL), indicating good biocompatibility of VANP. In summary, VANP is a potential formulation for the development of an LADS against osteomyelitis with optimal antibacterial efficacy, good bone resorbability, and biocompatibility. PMID

  12. The therapeutic potential of vaginal drug delivery in the treatment of cervical cancer.

    PubMed

    McConville, Christopher

    2015-01-01

    Cervical cancer is usually treated by surgery, with the more advanced cancers requiring adjuvant chemo or radiotherapy. Its location makes it easily accessible through the vagina for the localized delivery of chemotherapeutic drugs. Localized delivery has the advantage of direct delivery to the site of action resulting in a lower dose being required and a reduction in systemic side effects. This approach would be advantageous in fertility-sparing surgery, where by localized delivery could be used to reduce tumor size allowing for a much smaller tumor to be removed, reducing the risk of preterm birth. Furthermore, localized delivery could be used after surgery to reduce the risk of recurrence, which is significantly higher in fertility-sparing surgery compared with standard surgery. PMID:26001173

  13. Interval From Imaging to Treatment Delivery in the Radiation Surgery Age: How Long Is Too Long?

    SciTech Connect

    Seymour, Zachary A.; Fogh, Shannon E.; Westcott, Sarah K.; Braunstein, Steve; Larson, David A.; Barani, Igor J.; Nakamura, Jean; Sneed, Penny K.

    2015-09-01

    Purpose: The purpose of this study was to evaluate workflow and patient outcomes related to frameless stereotactic radiation surgery (SRS) for brain metastases. Methods and Materials: We reviewed all treatment demographics, clinical outcomes, and workflow timing, including time from magnetic resonance imaging (MRI), computed tomography (CT) simulation, insurance authorization, and consultation to the start of SRS for brain metastases. Results: A total of 82 patients with 151 brain metastases treated with SRS were evaluated. The median times from consultation, insurance authorization, CT simulation, and MRI for treatment planning were 15, 7, 6, and 11 days to SRS. Local freedom from progression (LFFP) was lower in metastases with MRI ≥14 days before treatment (P=.0003, log rank). The 6- and 12-month LFFP rate were 95% and 75% for metastasis with interval of <14 days from MRI to treatment compared to 56% and 34% for metastases with MRI ≥14 days before treatment. On multivariate analysis, LFFP remained significantly lower for lesions with MRI ≥14 days at SRS (P=.002, Cox proportional hazards; hazard ratio: 3.4, 95% confidence interval: 1.6-7.3). Conclusions: Delay from MRI to SRS treatment delivery for brain metastases appears to reduce local control. Future studies should monitor the timing from imaging acquisition to treatment delivery. Our experience suggests that the time from MRI to treatment should be <14 days.

  14. New avenues for improving pancreatic ductal adenocarcinoma (PDAC) treatment: Selective stroma depletion combined with nano drug delivery.

    PubMed

    Bhaw-Luximon, Archana; Jhurry, Dhanjay

    2015-12-28

    The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell. The two opposing schools of thought - non-depletion of the stroma vs its depletion - to better drug efficacy are here discussed. Disrupting stroma-cancer cell interaction to reduce tumor progression and promote apoptosis is identified as the new direction of treatment for PDAC. Clinical data have shown that elimination of fibrosis and blockade of the Hedgehog pathway in stroma effectively promote drug delivery to tumor site and apoptosis. Reduced stiffness of ECM, lower fibrosis, higher permeability and higher blood flow after stroma depletion increase drug delivery. Combination strategies involving selective stroma depletion coupled with chemotherapy is currently proving to be the most efficient at clinical level. Striking the right balance between fibrosis depletion and angiogenesis promotion resulting in enhanced drug delivery and apoptosis is a major challenge. The use of nano drug delivery devices coupled with stroma depletion is emerging as the next phase treatment for PDAC. The breakthrough to combat PDAC will likely be a combination of early diagnosis and the emerging chemotherapy strategies. PMID:26415628

  15. Liposome-based co-delivery of siRNA and docetaxel for the synergistic treatment of lung cancer.

    PubMed

    Qu, Mei-Hua; Zeng, Rui-Fang; Fang, Shi; Dai, Qiang-Sheng; Li, He-Ping; Long, Jian-Ting

    2014-10-20

    Combination of more than one therapeutic strategy is the standard treatment in clinics. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a nanoparticulate system will suppress the tumor growth. In the present study, docetaxel (DTX) and BCL-2 siRNA was incorporated in a PEGylated liposome to systemically deliver in a lung cancer model (A549). The resulting nanoparticle (lipo-DTX/siRNA) was stable and exhibited a sustained release profile. The co-delivery of therapeutic moieties inhibited the cell proliferation (A549 and H226) in a time-dependent manner. Moreover, the co-delivery system of DTX and siRNA exhibited a remarkable apoptosis of cancer cells with elevated levels of caspase 3/7 activity (apoptosis markers). Cell cycle analysis further showed remarkable increase in sub-G0/G1 phase, indicating increasing hypodiploids or apoptotic cells. Pharmacokinetic study showed a long circulating profile for DTX from lipo-DTX/siRNA system facilitating the passive tumor targeting. In vivo antitumor study on A549 cell bearing xenograft tumor model exhibited a remarkable tumor regression profile for lipo-DTX/siRNA with 100% survival rate. The favorable tumor inhibition response was attributed to the synergistic effect of DTX potency and MDR reversing ability of BCL-2 siRNA in the tumor mass. Overall, experimental results suggest that co-delivery of DTX and siRNA could be promising approach in the treatment of lung cancers. PMID:25138252

  16. The role of treatment delivery factors in exposure-based cognitive behavioral therapy for panic disorder with agoraphobia.

    PubMed

    Weck, Florian; Grikscheit, Florian; Höfling, Volkmar; Kordt, Anne; Hamm, Alfons O; Gerlach, Alexander L; Alpers, Georg W; Arolt, Volker; Kircher, Tilo; Pauli, Paul; Rief, Winfried; Lang, Thomas

    2016-08-01

    Treatment delivery factors (i.e., therapist adherence, therapist competence, and therapeutic alliance) are considered to be important for cognitive behavioral therapy (CBT) for panic disorder and agoraphobia (PD/AG). In the current study, four independent raters conducted process evaluations based on 168 two-hour videotapes of 84 patients with PD/AG treated with exposure-based CBT. Two raters evaluated patients' interpersonal behavior in Session 1. Two raters evaluated treatment delivery factors in Session 6, in which therapists provided the rationale for conducting exposure exercises. At the 6-month follow-up, therapists' adherence (r=0.54) and therapeutic alliance (r=0.31) were significant predictors of changes in agoraphobic avoidance behavior; therapist competence was not associated with treatment outcomes. Patients' interpersonal behavior in Session 1 was a significant predictor of the therapeutic alliance in Session 6 (r=0.17). The findings demonstrate that treatment delivery factors, particularly therapist adherence, are relevant to the long-term success of CBT for PD/AG. PMID:27235836

  17. Articulating feedstock delivery device

    DOEpatents

    Jordan, Kevin

    2013-11-05

    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.

  18. Biogas production from pear residues using sludge from a wastewater treatment plant digester. Influence of the feed delivery procedure.

    PubMed

    Arhoun, B; Bakkali, A; El Mail, R; Rodriguez-Maroto, J M; Garcia-Herruzo, F

    2013-01-01

    Clear economic advantages may be obtained from the management of seasonal fruit wastes by codigestion at existing facilities which are working throughout the year with other residues. We have explored the biomethanization of pear residues in a 5L stirred reactor loaded with sludge from the anaerobic digester of a municipal wastewater treatment plant. Different organic loading rates (OLRs) of fruit waste were tested with two delivery procedures: a discontinuous one (fed once a day) and a pseudocontinuous one. For both procedures, as the OLR increases the pH of the digester drops to acidic values and large OLRs may cause the reactor failure. Nevertheless, the pseudocontinuous delivery allows the treatment of more residue, (10.5 versus 6.0 g of volatile solids per litre of reactor and day), maintaining the specific biogas production (0.44 L of biogas per gram of volatile solids), with some improvement in methane concentration (44% vs 39%). PMID:23131648

  19. Chronomodulated drug delivery system of urapidil for the treatment of hypertension

    PubMed Central

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

    2015-01-01

    Introduction: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. Materials and methods: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. Results: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. Conclusions: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension. PMID:25838996

  20. Numerical optimization of targeted delivery of charged nanoparticles to the ostiomeatal complex for treatment of rhinosinusitis

    PubMed Central

    Xi, Jinxiang; Yuan, Jiayao Eddie; Si, Xiuhua April; Hasbany, James

    2015-01-01

    Background Despite the prevalence of rhinosinusitis that affects 10%–15% of the population, current inhalation therapy shows limited efficacy. Standard devices deliver <5% of the drugs to the sinuses due to the complexity of nose structure, secluded location of the sinus, poor ventilation, and lack of control of particle motions inside the nasal cavity. Methods An electric-guided delivery system was developed to guide charged particles to the ostiomeatal complex (OMC). Its performance was numerically assessed in an MRI-based nose–sinus model. Key design variables related to the delivery device, drug particles, and patient breathing were determined using sensitivity analysis. A two-stage optimization of design variables was conducted to obtain the best performance of the delivery system using the Nelder-Mead algorithm. Results and discussion The OMC delivery system exhibited high sensitivity to the applied electric field and electrostatic charges carried by the particles. Through the synthesis of electric guidance and point drug release, the new delivery system eliminated particle deposition in the nasal valve and turbinate regions and significantly enhanced the OMC doses. An OMC delivery efficiency of 72.4% was obtained with the optimized design, which is one order of magnitude higher than the standard nasal devices. Moreover, optimization is imperative to achieve a sound delivery protocol because of the large number of design variables. The OMC dose increased from 45.0% in the baseline model to 72.4% in the optimized system. The optimization framework developed in this study can be easily adapted for the delivery of drugs to other sites in the nose such as the ethmoid sinus and olfactory region. PMID:26257521

  1. Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy

    NASA Astrophysics Data System (ADS)

    Janek Strååt, Sara; Andreassen, Björn; Jonsson, Cathrine; Noz, Marilyn E.; Maguire, Gerald Q., Jr.; Näfstadius, Peder; Näslund, Ingemar; Schoenahl, Frederic; Brahme, Anders

    2013-08-01

    The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 ± (0.5) cm misalignment was observed in the cranial-caudal direction of the patient between the induced activity distribution and treatment plan, indicating a beam patient setup error. No misalignment of this kind was seen in the prostate cancer patient. However, due to a fast patient setup error in the PET/CT scanner a slight mis-position of the patient in the PET/CT was observed in all three planes, resulting in a deformed activity distribution compared to the treatment plan. The present study indicates that the induced positron emitters by high energy photon beams can be measured quite accurately using PET imaging of subcutaneous fat to allow portal verification of the delivered treatment beams. Measurement of the induced activity in the patient 7 min after receiving 5 Gy involved count rates which were about

  2. Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy.

    PubMed

    Janek Strååt, Sara; Andreassen, Björn; Jonsson, Cathrine; Noz, Marilyn E; Maguire, Gerald Q; Näfstadius, Peder; Näslund, Ingemar; Schoenahl, Frederic; Brahme, Anders

    2013-08-21

    The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 ± (0.5) cm misalignment was observed in the cranial-caudal direction of the patient between the induced activity distribution and treatment plan, indicating a beam patient setup error. No misalignment of this kind was seen in the prostate cancer patient. However, due to a fast patient setup error in the PET/CT scanner a slight mis-position of the patient in the PET/CT was observed in all three planes, resulting in a deformed activity distribution compared to the treatment plan. The present study indicates that the induced positron emitters by high energy photon beams can be measured quite accurately using PET imaging of subcutaneous fat to allow portal verification of the delivered treatment beams. Measurement of the induced activity in the patient 7 min after receiving 5 Gy involved count rates which were about

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. Design and construction of a DNA origami drug delivery system based on MPT64 antibody aptamer for tuberculosis treatment

    PubMed Central

    Ranjbar, Reza; Hafezi-Moghadam, Mohammad Sadegh

    2016-01-01

    Introduction With all of the developments on infectious diseases, tuberculosis (TB) remains a cause of death among people. One of the most promising assembly techniques in nano-technology is “scaffolded DNA origami” to design and construct a nano-scale drug delivery system. Because of the global health problems of tuberculosis, the development of potent new anti-tuberculosis drug delivery system without cross-resistance with known anti-mycobacterial agents is urgently needed. The aim of this study was to design a nano-scale drug delivery system for TB treatment using the DNA origami method Methods In this study, we presented an experimental research on a DNA drug delivery system for treating Tuberculosis. TEM images were visualized with an FEI Tecnai T12 BioTWIN at 120 kV. The model was designed by caDNAno software and computational prediction of the 3D solution shape and its flexibility was calculated with a CanDo server. Results Synthesizing the product was imaged using transmission electron microscopy after negative-staining by uranyl formate. Conclusion We constructed a multilayer 3D DNA nanostructure system by designing square lattice geometry with the scaffolded-DNA-origami method. With changes in the lock and key sequences, we recommend that this system be used for other infectious diseases to target the pathogenic bacteria. PMID:27053991

  6. Current nanotechnological approaches for an effective delivery of bio-active drug molecules in the treatment of acne.

    PubMed

    Garg, Tarun

    2016-01-01

    Acne is a chronic inflammatory human skin disease, characterized by areas of skin with seborrhoea, comedones, papules, nodules, pimples, and possibly scarring with lesions occurring on face, neck, and back. Nanotechnological approaches such as particulate (solid lipid nanoparticles and microspheres), vesicular (liposomes and niosomes), colloidal drug delivery systems (micro-emulsion and nano-emulsion), and miscellaneous systems (aerosol foams and micro-sponges) have an important place in acne therapy. These approaches have an enormous opportunity for the designing of a novel, low-dose and effective treatment systems to control acne disease. In this review, we specially focus on the different nanotechnological approaches for an effective treatment of acne. PMID:24844191

  7. [Transcatheter delivery of recombinant adenovirus vector containing exogenous aquaporin gene in treatment of Sjögren's syndrome].

    PubMed

    Hong, H E; Jieqiong, Zhang; Yan, Fan; Xiaoshuang, Sun; Yuhao, Zhu

    2016-05-25

    Sjögren's syndrome is a kind of autoimmune disease, whose main clinical symptoms are dry mouth, dry eye and chronic parotid glandular inflammation. The conservative treatments include artificial tears or saliva,oral administration of corticosteroids,and immunosuppressantsl with limited effectiveness. Along with the development of molecular biology, vast attentions are being paid to researches on gene therapy for Sjögren's syndrome, hopefully to bring gospel to patients with Sjögren's syndrome. This article reviews the recent research progresses on transcatheter delivery of recombinant adenovirus vector with aquaporin gene in experimental treatment of Sjögren's syndrome. PMID:27045247

  8. Motion management during IMAT treatment of mobile lung tumors—A comparison of MLC tracking and gated delivery

    PubMed Central

    Falk, Marianne; Pommer, Tobias; Keall, Paul; Korreman, Stine; Persson, Gitte; Poulsen, Per; Munck af Rosenschöld, Per

    2014-01-01

    Purpose: To compare real-time dynamic multileaf collimator (MLC) tracking, respiratory amplitude and phase gating, and no compensation for intrafraction motion management during intensity modulated arc therapy (IMAT). Methods: Motion management with MLC tracking and gating was evaluated for four lung cancer patients. The IMAT plans were delivered to a dosimetric phantom mounted onto a 3D motion phantom performing patient-specific lung tumor motion. The MLC tracking system was guided by an optical system that used stereoscopic infrared (IR) cameras and five spherical reflecting markers attached to the dosimetric phantom. The gated delivery used a duty cycle of 35% and collected position data using an IR camera and two reflecting markers attached to a marker block. Results: The average gamma index failure rate (2% and 2 mm criteria) was <0.01% with amplitude gating for all patients, and <0.1% with phase gating and <3.7% with MLC tracking for three of the four patients. One of the patients had an average failure rate of 15.1% with phase gating and 18.3% with MLC tracking. With no motion compensation, the average gamma index failure rate ranged from 7.1% to 46.9% for the different patients. Evaluation of the dosimetric error contributions showed that the gated delivery mainly had errors in target localization, while MLC tracking also had contributions from MLC leaf fitting and leaf adjustment. The average treatment time was about three times longer with gating compared to delivery with MLC tracking (that did not prolong the treatment time) or no motion compensation. For two of the patients, the different motion compensation techniques allowed for approximately the same margin reduction but for two of the patients, gating enabled a larger reduction of the margins than MLC tracking. Conclusions: Both gating and MLC tracking reduced the effects of the target movements, although the gated delivery showed a better dosimetric accuracy and enabled a larger reduction of the

  9. Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

    PubMed

    Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; Lőbenberg, Raimar; Doschak, Michael R

    2015-12-01

    Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation. In the following review, we evaluate transdermal drug delivery systems, with a particular focus on delivering therapeutic agents to treat superficial bone pain, notably stress fractures. We further introduce and discuss several small peptide hormones active in bone (such as calcitonins and parathyroid hormone) that have shown potential for transdermal delivery, often under the added augmentation of transdermal drug delivery systems that employ lipo/hydrophilicity, electric charge, and/or microprojection facilitation across the skin barrier. PMID:26350235

  10. Spatial Modeling of Drug Delivery Routes for Treatment of Disseminated Ovarian Cancer.

    PubMed

    Winner, Kimberly R Kanigel; Steinkamp, Mara P; Lee, Rebecca J; Swat, Maciej; Muller, Carolyn Y; Moses, Melanie E; Jiang, Yi; Wilson, Bridget S

    2016-03-15

    In ovarian cancer, metastasis is typically confined to the peritoneum. Surgical removal of the primary tumor and macroscopic secondary tumors is a common practice, but more effective strategies are needed to target microscopic spheroids persisting in the peritoneal fluid after debulking surgery. To treat this residual disease, therapeutic agents can be administered by either intravenous or intraperitoneal infusion. Here, we describe the use of a cellular Potts model to compare tumor penetration of two classes of drugs (cisplatin and pertuzumab) when delivered by these two alternative routes. The model considers the primary route when the drug is administered either intravenously or intraperitoneally, as well as the subsequent exchange into the other delivery volume as a secondary route. By accounting for these dynamics, the model revealed that intraperitoneal infusion is the markedly superior route for delivery of both small-molecule and antibody therapies into microscopic, avascular tumors typical of patients with ascites. Small tumors attached to peritoneal organs, with vascularity ranging from 2% to 10%, also show enhanced drug delivery via the intraperitoneal route, even though tumor vessels can act as sinks during the dissemination of small molecules. Furthermore, we assessed the ability of the antibody to enter the tumor by in silico and in vivo methods and suggest that optimization of antibody delivery is an important criterion underlying the efficacy of these and other biologics. The use of both delivery routes may provide the best total coverage of tumors, depending on their size and vascularity. PMID:26719526

  11. The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview.

    PubMed

    Djupesland, Per G; Messina, John C; Mahmoud, Ramy A

    2014-06-01

    The intricate pathophysiology of brain disorders, difficult access to the brain, and the complexity and high risks and costs of drug development represent major hurdles for improving therapies. Nose-to-brain drug transport offers an attractive alternative or addition to formulation-only strategies attempting to enhance drug penetration into the CNS. Although still a matter of controversy, many studies in animals claim direct nose-to-brain transport along the olfactory and trigeminal nerves, circumventing the traditional barriers to CNS entry. Some clinical trials in man also suggest nose-to-brain drug delivery, although definitive proof in man is lacking. This review focuses on new nasal delivery technologies designed to overcome inherent anatomical and physiological challenges and facilitate more efficient and targeted drug delivery for CNS disorders. PMID:25090283

  12. Pregnancy and the Patient with Inflammatory Bowel Disease: Fertility, Treatment, Delivery, and Complications.

    PubMed

    McConnell, Ryan A; Mahadevan, Uma

    2016-06-01

    For many women with inflammatory bowel disease (IBD), the illness coincides with their childbearing years. IBD increases the risk of pregnancy complications and adverse pregnancy outcomes. The multidisciplinary care team should emphasize the importance of medication adherence to achieve preconception disease control and maintain corticosteroid-free remission throughout pregnancy. Medication adjustments to reduce fetal exposure may be considered on an individualized basis in quiescent disease; however, any benefits of such adjustments remain theoretic and there is risk of worsening disease activity. Mode of delivery is determined by obstetric indications, except for women with active perianal disease who should consider cesarean delivery. PMID:27261899

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

    PubMed

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

    2014-06-01

    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

  14. Nanocarrier-based co-delivery of small molecules and siRNA/miRNA for treatment of cancer.

    PubMed

    Chitkara, Deepak; Singh, Saurabh; Mittal, Anupama

    2016-04-01

    Aberrant gene expression can trigger several vital molecular events that not only result in carcinogenesis but also cause chemoresistance, metastasis and relapse. Gene-based therapies using siRNA/miRNA have been suggested as new treatment method to improve the current regimen. Although these agents can restore the normal molecular cascade thereby resensitizing the cancer cells, delivering a standard regimen (either subsequently or simultaneously) is necessary to achieve the therapeutic benefit. However, co-delivery using a single carrier could give an additional advantage of similar biodistribution profile of the loaded agents. While much research has been carried out in this field in recent years, challenges involved in designing combination formulations including efficient coloading, stability, appropriate biodistribution and target specificity have hampered their clinical translation. This article highlights current aspects of nano-carriers used for co-delivery of small molecules and genes to treat cancer. PMID:27010986

  15. Pharmacological evaluation of nasal delivery of selegiline hydrochloride-loaded thiolated chitosan nanoparticles for the treatment of depression.

    PubMed

    Singh, Devendra; Rashid, Muzamil; Hallan, Supandeep Singh; Mehra, Neelesh Kumar; Prakash, Atish; Mishra, Neeraj

    2016-05-01

    The aim of the present study was to investigate the propensity of thiolated chitosan nanoparticles (TCNs) to enhance the nasal delivery of selegiline hydrochloride. TCNs were synthesized by the ionic gelation method. The particle size distribution (PDI), entrapment efficiency (EE), and zeta potential of modified chitosan (CS) nanoparticles were found to be 215 ± 34.71 nm, 70 ± 2.71%, and + 17.06 mV, respectively. The forced swim and the tail suspension tests were used to evaluate the anti-depressant activity, in which elevated immobility time was found to reduce on treatment. TCNs seem to be promising candidates for nose-to-brain delivery in the evaluation of antidepressant activity. PMID:26042481

  16. Targeted drug delivery nanosystems based on copolymer poly(lactide)-tocopheryl polyethylene glycol succinate for cancer treatment

    NASA Astrophysics Data System (ADS)

    Thu Ha, Phuong; Nguyen, Hoai Nam; Doan Do, Hai; Thong Phan, Quoc; Nguyet Tran Thi, Minh; Phuc Nguyen, Xuan; Nhung Hoang Thi, My; Huong Le, Mai; Nguyen, Linh Toan; Quang Bui, Thuc; Hieu Phan, Van

    2016-03-01

    Along with the development of nanotechnology, drug delivery nanosystems (DDNSs) have attracted a great deal of concern among scientists over the world, especially in cancer treatment. DDNSs not only improve water solubility of anticancer drugs but also increase therapeutic efficacy and minimize the side effects of treatment methods through targeting mechanisms including passive and active targeting. Passive targeting is based on the nano-size of drug delivery systems while active targeting is based on the specific bindings between targeting ligands attached on the drug delivery systems and the unique receptors on the cancer cell surface. In this article we present some of our results in the synthesis and testing of DDNSs prepared from copolymer poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS), which carry anticancer drugs including curcumin, paclitaxel and doxorubicin. In order to increase the targeting effect to cancer cells, active targeting ligand folate was attached to the DDNSs. The results showed copolymer PLA-TPGS to be an excellent carrier for loading hydrophobic drugs (curcumin and paclitaxel). The fabricated DDNSs had a very small size (50-100 nm) and enhanced the cellular uptake and cytotoxicity of drugs. Most notably, folate-decorated paclitaxel-loaded copolymer PLA-TPGS nanoparticles (Fol/PTX/PLA-TPGS NPs) were tested on tumor-bearing nude mice. During the treatment time, Fol/PTX/PLA-TPGS NPs always exhibited the best tumor growth inhibition compared to free paclitaxel and paclitaxel-loaded copolymer PLA-TPGS nanoparticles. All results evidenced the promising potential of copolymer PLA-TPGS in fabricating targeted DDNSs for cancer treatment.

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

    PubMed

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

    2016-03-01

    Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross-linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericin's photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems. PMID:26900631

  18. Overview of insulin and non-insulin delivery devices in the treatment of diabetes.

    PubMed

    Pisano, Michele

    2014-12-01

    Antidiabetic agents can be delivered orally or with a syringe, but other options are also available, such as insulin and non-insulin pen devices and insulin pumps. This article reviews the available delivery devices and their current place in therapy. PMID:25516696

  19. Novel delivery systems for anti-allergic agents: allergic disease and innovative treatments.

    PubMed

    Lopes, Carla M; Coelho, Pedro B; Oliveira, Rita

    2015-01-01

    Anti-allergic agents are used to treat a great variety of diseases which usually involve an inflammation reaction. These compounds act by inhibiting the release and the effects of inflammatory mediators (e.g. histamine) in the target tissue. The purpose of anti-allergy therapy is to deliver the drug to its local of action in a therapeutic concentration, minimizing the undesired side effects. In order to solve some of the anti-allergic agents' physicochemical drawbacks and the limitations associated to conventional pharmaceutical formulations (e.g. poor solubility and absorption, skin permeation, stability), novel drug delivery systems, such as cyclodextrins, liposomes, micelles, microemulsions, nano and microparticles, have been developed. Depending on the allergic condition, several administration routes are used to deliver anti-allergic agents, each with its own disadvantages to overcome. In the literature, there are a vast number of papers concerning novel delivery systems for anti-allergic agents, making it difficult to evaluate the information and the promising outcomes. The aim of the present review article is to compile the recent (i.e. in the new millennium) improvements of novel drug delivery technology focusing on the achievement of anti-allergic therapeutic delivery. The potential intrinsic benefits of these systems will reflect an increased therapeutic adherence and better patients' life quality. A critical prospect of future clinical trial directions will also be discussed. PMID:25895551

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

    ERIC Educational Resources Information Center

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

    2009-01-01

    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…

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

    SciTech Connect

    Keall, Paul J. Chang, Michael; Benedict, Stanley; Thames, Howard; Vedam, S. Sastry; Lin, Peck-Sun

    2008-08-01

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

  2. SU-F-BRE-10: Methods to Simulate and Measure the Attenuation for Modeling a Couch Top with Rails for FFF Treatment Delivery On the Varian Edge Linac

    SciTech Connect

    Gulam, M; Gardner, S; Zhao, B; Snyder, K; Song, K; Li, H; Gordon, J; Wen, N; Chetty, I; Kearns, W

    2014-06-15

    Purpose: To measure attenuation for modelling of the KVue Couchtop for 6X and 10X FFF SRS/SBRT treatment Methods: Treatment planning simulation studies were done using 6X FFF beams to estimate the dosimetric impact of KVue couchtops (including the Q-Fix IGRT [carbon fiber] and Calypso [nonconductive Kevlar material]) with a structure model obtained from a research workstation (Eclipse, advanced planning interface (API) v13). Prior to installation on the Varian Edge linac, the couchtop along with (Kevlar) rails were CT scanned with the rails at various positions. An additional scan with the couchtop 15cm above the CT table top was obtained with 20cm solid water to facilitate precised/indexed data acquisition. Measurements for attenuation were obtained for field sizes of 2, 4 and 10 cm{sup 2} at 42 gantry angles including 6 pairs of opposing fields and other angles for oblique delivery where the beams traversed the couchtop and or rails. The delivery was fully automated with xml scripts running in developer mode. The results were then used to determine an accurate structure model for AAA (Eclipse v11) planning of IMRT and RapidArc delivery. Results: The planning simulation relative dose attenuation for oblique entry was not significantly different than the Exact IGRT or BrainLab iBeam couch except that the rails added 6% additional attenuation. The relative attenuation measurements for PA, PA (rails: inner position), oblique, oblique (rails: outer position), oblique (rails: inner position) were: −2.0%, −2.5%, −15.6%, −2.5%, −5.0% for 6X FFF and −1.4%, −1.5%, −12.2%, − 2.5%, −5.0% for 10X FFF with slight decrease in attenuation versus field size. A Couch structure model (with HU values) was developed. Calculation compared to measurement showed good agreement except for oblique (rails: outer position) where differences approached a magnitude of 6%. Conclusion: A model of the couch structures has been developed accounting for attenuation for FFF

  3. Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

    SciTech Connect

    Water, Steven van de; Kooy, Hanne M.; Heijmen, Ben J.M.; Hoogeman, Mischa S.

    2015-06-01

    Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.

  4. Systemic delivery of messenger RNA for the treatment of pancreatic cancer using polyplex nanomicelles with a cholesterol moiety.

    PubMed

    Uchida, Satoshi; Kinoh, Hiroaki; Ishii, Takehiko; Matsui, Akitsugu; Tockary, Theofilus Agrios; Takeda, Kaori Machitani; Uchida, Hirokuni; Osada, Kensuke; Itaka, Keiji; Kataoka, Kazunori

    2016-03-01

    Systemic delivery of messenger RNA (mRNA) is technically challenging because mRNA is highly susceptible to enzymatic degradation in the blood circulation. In this study, we used a nanomicelle-based platform, prepared from mRNA and poly(ethylene glycol) (PEG)-polycation block copolymers. A cholesterol (Chol) moiety was attached to the ω-terminus of the block copolymer to increase the stability of the nanomicelle by hydrophobic interaction. After in vitro screening, polyaspartamide with four aminoethylene repeats in its side chain (PAsp(TEP)) was selected as the cationic segment of the block copolymer, because it contributes to enhance nuclease resistance and high protein expression from the mRNA. After intravenous injection, PEG-PAsp(TEP)-Chol nanomicelles showed significantly enhanced blood retention of mRNA in comparison to nanomicelles without Chol. We used the nanomicelles for treating intractable pancreatic cancer in a subcutaneous inoculation mouse model through the delivery of mRNA encoding an anti-angiogenic protein (sFlt-1). PEG-PAsp(TEP)-Chol nanomicelles generated efficient protein expression from the delivered mRNA in tumor tissue, resulting in remarkable inhibition of the tumor growth, whereas nanomicelles without Chol failed to show a detectable therapeutic effect. In conclusion, the stabilized nanomicelle system led to the successful systemic delivery of mRNA in therapeutic application, holding great promise for the treatment of various diseases. PMID:26763736

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

    SciTech Connect

    Moldovan, Monica; Fontenot, Jonas D.; Gibbons, John P.; Lee, Tae Kyu; Rosen, Isaac I.; Fields, Robert S.; Hogstrom, Kenneth R.

    2011-01-01

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

  6. Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment

    PubMed Central

    Aini, Hailati; Itaka, Keiji; Fujisawa, Ayano; Uchida, Hirokuni; Uchida, Satoshi; Fukushima, Shigeto; Kataoka, Kazunori; Saito, Taku; Chung, Ung-il; Ohba, Shinsuke

    2016-01-01

    Osteoarthritis (OA) is a chronic degenerative joint disease and a major health problem in the elderly population. No disease-modifying osteoarthritis drug (DMOAD) has been made available for clinical use. Here we present a disease-modifying strategy for OA, focusing on messenger RNA (mRNA) delivery of a therapeutic transcription factor using polyethylene glycol (PEG)-polyamino acid block copolymer-based polyplex nanomicelles. When polyplex nanomicelles carrying the cartilage-anabolic, runt-related transcription factor (RUNX) 1 mRNA were injected into mouse OA knee joints, OA progression was significantly suppressed compared with the non-treatment control. Expressions of cartilage-anabolic markers and proliferation were augmented in articular chondrocytes of the RUNX1-injected knees. Thus, this study provides a proof of concept of the treatment of degenerative diseases such as OA by the in situ mRNA delivery of therapeutic transcription factors; the presented approach will directly connect basic findings on disease-protective or tissue-regenerating factors to disease treatment. PMID:26728350

  7. Measuring the Integration of Tobacco Policy and Treatment into the Behavioral Health Care Delivery System: How Are We Doing?

    PubMed

    Christiansen, Bruce A; Macmaster, David R; Heiligenstein, Eric L; Glysch, Randal L; Riemer, Donna M; Adsit, Robert T; Hayden, Kristine A; Hollenback, Christopher P; Fiore, Michael C

    2016-01-01

    People with a mental illness and/or drug use disorder have a higher rate of smoking than adults in general. To address this challenge, recommendations include integrating tobacco-free policies and tobacco dependency treatment into the behavioral health care delivery system. Currently, little is known regarding levels of such integration. A 65-item Internet survey measuring integration assessed three areas: a) policies addressing the use of tobacco products; b) provision of evidence-based tobacco dependence treatment; and, c) capacity to help employees/volunteers quit tobacco use. The survey was distributed to representatives of all behavioral health programs in Wisconsin. The survey response rate was 27.1%. Programs, on average, were 40% integrated. A significant proportion of programs (20%) were less than 20% integrated. A few programs (4.3%) exceeded 80% integration. Integration of tobacco policies and treatment into the behavioral health care delivery system remains limited and there is a need for technical assistance and training. PMID:27180692

  8. Patient Satisfaction with Methadone Maintenance Treatment in Vietnam: A Comparison of Different Integrative-Service Delivery Models

    PubMed Central

    Tran, Bach Xuan; Nguyen, Long Hoang; Phan, Huong Thu Thi; Latkin, Carl A.

    2015-01-01

    Background Patient satisfaction is an important component of quality in healthcare delivery. To inform the expansion of Methadone Maintenance Treatment (MMT) services in Vietnam, we examined the satisfaction of patients with regards to different services delivery models and identified its associated factors. Methods We interviewed 1,016 MMT patients at 5 clinics in Hanoi and Nam Dinh province. The modified SATIS instrument, a 10-item scale, was used to measure three dimensions: “Services quality and convenience”, “Health workers’ capacity and responsiveness” and “Inter-professional care”. Results The average score was high across three SATIS dimensions. However, only one third of patients completely satisfied with general health services and treatment outcomes. Older age, higher education, having any problem in self-care and anxiety/depression were negatively associated with patient’s satisfaction. Meanwhile, patients receiving MMT at clinics, where more comprehensive HIV and general health care services were available, were more likely to report a complete satisfaction. Conclusion Patients were highly satisfied with MMT services in Vietnam. However, treatment for drug users should go beyond methadone maintenance to address complicated health demands of drug users. Integrating MMT with comprehensive HIV and general health services together with improving the capacity of health workers and efficiency of services organisation to provide interconnected health care for drug users are critical for improving the outcomes of the MMT program. PMID:26556036

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

    PubMed Central

    2010-01-01

    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

  10. Lipopolyplex for Therapeutic Gene Delivery and Its Application for the Treatment of Parkinson’s Disease

    PubMed Central

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

    2016-01-01

    Lipopolyplex is a core-shell structure composed of nucleic acid, polycation and lipid. As a non-viral gene delivery vector, lipopolyplex combining the advantages of polyplex and lipoplex has shown superior colloidal stability, reduced cytotoxicity, extremely high gene transfection efficiency. Following intravenous administration, there are many strategies based on lipopolyplex to overcome the complex biological barriers in systemic gene delivery including condensation of nucleic acids into nanoparticles, long circulation, cell targeting, endosomal escape, release to cytoplasm and entry into cell nucleus. Parkinson’s disease (PD) is the second most common neurodegenerative disorder and severely influences the patients’ life quality. Current gene therapy clinical trials for PD employing viral vectors didn’t achieve satisfactory efficacy. However, lipopolyplex may become a promising alternative approach owing to its stability in blood, ability to cross the blood-brain barrier (BBB) and specific targeting to diseased brain cells. PMID:27092073

  11. Influence of spasmolytic treatment and amniotomy on delivery times: a factorial clinical trial.

    PubMed

    Guerresi, E; Gori, G; Beccari, A; Farro, M; Mazzanti, C

    1981-01-01

    In a double-blind factorial clinical trial in 300 patients (150 primiparae and 150 multiparae), the effects of amniotomy, rociverine, and butylscopolamine bromide administration on the course of labor were investigated. Rociverine significantly reduced the dilatation time and had no effect on the delivery time. Butylscopolamine bromide had no appreciable effect on the dilatation and expulsion times. Amniotomy resulted in a lengthening of the dilatation time and no significant change in the expulsion time. PMID:7008940

  12. Theoretical Approaches to Lentiviral Mediated Neurotrophin Delivery in Potential Treatments of Parkinson’s Disease

    PubMed Central

    Qudrat, Anam; Unni, Netra

    2016-01-01

    Parkinson’s disease is a late-onset neurodegenerative disease, characterized by both motor and non-motor symptoms. Motor symptoms include postural instability, rigidity, and tremor, while non-motor symptoms include anxiety, dementia, and depression. In this integrative review, we discuss PD disease pathophysiology in detail and introduce how neurotrophic growth factor delivery via a retroviral-based system can be used as efficacious tools for targeted gene therapy. PMID:27354847

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

    PubMed

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

    2012-01-01

    Periodontitis is a complex disease and bacterial infection is one of the most common factors involved in this disease. Current strategies for the local delivery of antibiotics do not allow a complete clearance of bacteria filling dentinal tubules and this limits their therapeutic efficacy. Therefore, there is a strong need for the development of new delivery strategies aimed at improving the efficacy of antibiotic therapy for periodontitis with special reference to their ability to penetrate into the tubules. The aim of the present study is to develop liposome-based delivery systems of sub-micron dimension, able to diffuse into the dentinal tubules. A further aim of the research is to develop a protocol for enhanced diffusion based on the use of magnetic liposomes and magnetic fields. Liposomes were produced by hydration of a pre-liposomal formulation. The vesicles were stabilised with PEG and their re-sizing was achieved by extrusion. Magnetite nanoparticles were synthesized inside the vesicles, i.e., the chemical reaction involving FeCl₂, FeCl₃ and NH₃ occurred within the core of the newly formed liposomes. Dynamic light scattering analysis was performed for size characterization. A mathematical model was implemented to predict the diffusion of the liposomes in dentinal tubules. Ex-vivo validation was performed on extracted human teeth. We produced PEG-ylated liposomes (average size 204.3 nm) and PEG-ylated magnetic liposomes (average size 286 nm) and an iron content of 4.2 μg/ml. Through mathematical modelling, we deduced that sub-micrometer vesicles are able to penetrate into dentinal tubules. This penetration is considerably more effective when the vesicles are magnetized and subjected to an external magnetic field which accelerates their movement within the tubules. The liposome-based delivery systems developed by the present study are able to penetrate deeply into the tubules, sometimes reaching their terminal ends. PMID:23058016

  14. Synergistic Nanomedicine: Passive, Active, and Ultrasound-Triggered Drug Delivery in Cancer Treatment.

    PubMed

    Elkhodiry, Mohamed A; Momah, Christian C; Suwaidi, Shaima R; Gadalla, Dina; Martins, Ana M; Vitor, Rute F; Husseini, Ghaleb A

    2016-01-01

    Nanocarriers are heavily researched as drug delivery vehicles capable of sequestering antineoplastic agents and then releasing their contents at the desired location. The feasibility of using such carriers stems from their ability to produce a multimodel delivery system whereby passive, ligand and triggered targeting can be applied in the fight against cancer. Passive targeting capitalizes on the leaky nature of tumor tissue which allows for the extravasation of particles with a size smaller than 0.5 µm into the tumors. Ligand targeting utilizes the concept of receptor-mediated endocytosis and involves the conjugation of ligands onto the surface of nanoparticles, while triggered targeting involves the use of external and internal stimuli to release the carriers contents upon reaching the diseased location. In this review, micelles and liposomes have been considered due to the promising results they have shown in vivo and in vitro and their potential for advancements into clinical trials. Thus, this review focuses on the most recent advancements in the field of micellar and liposomal drug delivery and considers the synergistic effect of passive- and ligand-targeting strategies, and the use of ultrasound in triggering drug release at the tumor site. PMID:27398430

  15. Microneedle-mediated delivery of donepezil: Potential for improved treatment options in Alzheimer's disease.

    PubMed

    Kearney, Mary-Carmel; Caffarel-Salvador, Ester; Fallows, Steven J; McCarthy, Helen O; Donnelly, Ryan F

    2016-06-01

    Transdermal drug delivery is an attractive route of drug administration; however, there are relatively few marketed transdermal products. To increase delivery across the skin, strategies to enhance skin permeability are widely investigated, with microneedles demonstrating particular promise. Hydrogel-forming microneedles are inserted into the skin, and following dissolution of a drug loaded reservoir and movement of the drug through the created channels, the microneedle array is removed intact, and can then be readily and safely discarded. This study presents the formulation and evaluation of an integrated microneedle patch containing the Alzheimer's drug, donepezil hydrochloride. The integrated patch consisted of hydrogel-forming microneedles in combination with a donepezil hydrochloride containing film. Formulation and characterisation of plasticised films, prepared from poly(vinylpyrrolidone) or poly (methyl vinyl ether co-maleic anhydride/acid) (Gantrez®) polymers, is presented. Furthermore, in vitro permeation of donepezil hydrochloride across neonatal porcine skin from the patches was investigated, with 854.71μg±122.71μg donepezil hydrochloride delivered after 24h, using the optimum patch formulation. Following administration of the patch to an animal model, plasma concentrations of 51.8±17.6ng/mL were obtained, demonstrating the success of this delivery platform for donepezil hydrochloride. PMID:27018330

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

    SciTech Connect

    Adamson, Justus; Wu Qiuwen

    2008-05-15

    Margin reduction for prostate radiotherapy is limited by uncertainty in prostate localization during treatment. We investigated the feasibility and accuracy of measuring prostate intrafraction motion using kV fluoroscopy performed simultaneously with radiotherapy. Three gold coils used for target localization were implanted into the patient's prostate gland before undergoing hypofractionated online image-guided step-and-shoot intensity modulated radiation therapy (IMRT) on an Elekta Synergy linear accelerator. At each fraction, the patient was aligned using a cone-beam computed tomography (CBCT), after which the IMRT treatment delivery and fluoroscopy were performed simultaneously. In addition, a post-treatment CBCT was acquired with the patient still on the table. To measure the intrafraction motion, we developed an algorithm to register the fluoroscopy images to a reference image derived from the post-treatment CBCT, and we estimated coil motion in three-dimensional (3D) space by combining information from registrations at different gantry angles. We also detected the MV beam turning on and off using MV scatter incident in the same fluoroscopy images, and used this information to synchronize our intrafraction evaluation with the treatment delivery. In addition, we assessed the following: the method to synchronize with treatment delivery, the dose from kV imaging, the accuracy of the localization, and the error propagated into the 3D localization from motion between fluoroscopy acquisitions. With 0.16 mAs/frame and a bowtie filter implemented, the coils could be localized with the gantry at both 0 deg. and 270 deg. with the MV beam off, and at 270 deg. with the MV beam on when multiple fluoroscopy frames were averaged. The localization in two-dimensions for phantom and patient measurements was performed with submillimeter accuracy. After backprojection into 3D the patient localization error was (-0.04{+-}0.30) mm, (0.09{+-}0.36) mm, and (0.03{+-}0.68) mm in the

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

    PubMed Central

    Adamson, Justus; Wu, Qiuwen

    2008-01-01

    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

  18. Drug delivery systems for ovarian cancer treatment: a systematic review and meta-analysis of animal studies

    PubMed Central

    Raavé, René; de Vries, Rob B.M.; Massuger, Leon F.; van Kuppevelt, Toin H.

    2015-01-01

    Current ovarian cancer treatment involves chemotherapy that has serious limitations, such as rapid clearance, unfavorable biodistribution and severe side effects. To overcome these limitations, drug delivery systems (DDS) have been developed to encapsulate chemotherapeutics for delivery to tumor cells. However, no systematic assessment of the efficacy of chemotherapy by DDS compared to free chemotherapy (not in a DDS) has been performed for animal studies. Here, we assess the efficacy of chemotherapy in DDS on survival and tumor growth inhibition in animal studies. We searched PubMed and EMBASE (via OvidSP) to systematically identify studies evaluating chemotherapeutics encapsulated in DDS for ovarian cancer treatment in animal studies. Studies were assessed for quality and risk of bias. Study characteristics were collected and outcome data (survival/hazard ratio or tumor growth inhibition) were extracted and used for meta-analyses. Meta-analysis was performed to identify and explore which characteristics of DDS influenced treatment efficacy. A total of 44 studies were included after thorough literature screening (2,735 studies found after initial search). The risk of bias was difficult to assess, mainly because of incomplete reporting. A total of 17 studies (377 animals) and 16 studies (259 animals) could be included in the meta-analysis for survival and tumor growth inhibition, respectively. In the majority of the included studies chemotherapeutics entrapped in a DDS significantly improved efficacy over free chemotherapeutics regarding both survival and tumor growth inhibition. Subgroup analyses, however, revealed that cisplatin entrapped in a DDS did not result in additional tumor growth inhibition compared to free cisplatin, although it did result in improved survival. Micelles did not show a significant tumor growth inhibition compared to free chemotherapeutics, which indicates that micelles may not be a suitable DDS for ovarian cancer treatment. Other

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

    PubMed Central

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

    2015-01-01

    Background Cervical cancer is the most common reproductive health cancer in Malawi. In most cases, women report to health facilities when the disease is in its advanced stage. In this study, we investigate service providers’ perceptions about barriers for women to access cervical cancer screening and early treatment services in Malawi. Methods We conducted in-depth interviews with 13 district coordinators and 40 service providers of cervical cancer screening and early treatment services in 13 districts in Malawi. The study was conducted in 2012. The district coordinators helped the research team identify the health facilities which were providing cervical cancer screening and early treatment services. Results Almost all informants reported that cervical cancer was a major public health problem in their districts and that prevention efforts for this disease were being implemented. They were aware of the test and treat approach using visual inspection with acetic acid (VIA). They, however, said that the delivery of cervical cancer screening and early treatment services was compromised because of factors such as gross shortage of staff, lack of equipment and supplies, the lack of supportive supervision, and the use of male service providers. Informants added that the lack of awareness about the disease among community members, long distances to health facilities, the lack of involvement of husbands, and prevailing misperceptions about the disease (eg, that it is caused by the exposure to the VIA process) affect the uptake of these services. Conclusion While progress has been made in the provision of cervical cancer screening and early treatment services in Malawi, a number of factors affect service delivery and uptake. There is a need to continue creating awareness among community members including husbands and also addressing identified barriers such as shortage of staff and supplies in order to improve uptake of services. PMID:25848229

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

    PubMed Central

    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

    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

  1. Ocular delivery of macromolecules

    PubMed Central

    Kim, Yoo-Chun; Chiang, Bryce; Wu, Xianggen; Prausnitz, Mark R.

    2014-01-01

    Biopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non--invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects. This review discusses the barriers to drug delivery via various ophthalmic routes of administration in the context of macromolecule delivery and discusses efforts to develop controlled-release systems for delivery of biopharmaceuticals to the eye. The growing number of macromolecular therapies in the eye needs improved drug delivery methods that increase drug efficacy, safety and patient compliance. PMID:24998941

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

    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.

  3. Local immunotherapy via delivery of interleukin-10 and transforming growth factor β antagonist for treatment of chronic kidney disease.

    PubMed

    Rodell, Christopher B; Rai, Reena; Faubel, Sarah; Burdick, Jason A; Soranno, Danielle E

    2015-05-28

    Obstructive nephropathy is the leading cause of kidney disease in children. The tissue injury resulting from initial dilation precipitates a deleterious cascade of macrophage infiltration, apoptosis, and fibrosis to produce a resultant dysfunctional tissue. We propose to abate this tissue remodeling process through immunotherapy administered via the local and sustained delivery of interleukin-10 (IL-10; anti-inflammatory) and anti-transforming growth factor β (anti-TGFβ; anti-fibrotic). Shear-thinning, injectable hyaluronic acid (HA) hydrogels were formed through supramolecular guest-host interactions and used to contain IL-10, anti-TGFβ, or both molecules together. Degradation assays demonstrated that diffusive molecule release was associated with concurrent hydrogel erosion and was sustained for up to 3weeks in vitro. Erosion was likewise monitored in vivo by non-invasive optical imaging, where gel localization to the affected tissue was observed with near complete clearance by day 18. Hydrogels were applied to a murine model of chronic kidney disease, with subcapsular hydrogel injections acting as a delivery depot. Quantitative histological analysis (days 7, 21, and 35) was used to evaluate treatment efficacy. Notably, results demonstrated reduced macrophage infiltration beyond day 7 in treatment groups and reduced apoptosis at day 21, relative to untreated unilateral ureteral obstruction disease model. Fibrosis was reduced at the 35day timepoint in groups treated with IL-10 or anti-TGFβ alone, but not with the combination therapy. Rather, dual delivery of IL-10 and anti-TGFβ resulted in a paradoxical hastening of fibrosis, warranting further investigation. Localized immunotherapy is a novel approach to treat kidney disease and shows promise as a translatable therapy. PMID:25804871

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

    PubMed Central

    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

    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

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

    PubMed

    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

    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

  6. 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

    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

    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. PMID:24667813

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

    PubMed

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

    2015-01-01

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

  8. A novel approach for lung delivery of rifampicin-loaded liposomes in dry powder form for the treatment of tuberculosis

    PubMed Central

    Patil, Jagadevappa S.; Devi, V. Kusum; Devi, Kshama; Sarasija, S.

    2015-01-01

    Background: Lung administration of antibiotics by nebulization is promising for improved treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, lipid particulate system may improve lung delivery. Materials and Methods: We investigated rifampicin-loaded freeze-dried liposomes. Various formulations were prepared with different drug lipid ratios and one formulation was optimized. Optimized colloidal liposome formulation was freeze-dried and subsequently subjected for various evaluation and characterization parameters such as in-vitro dissolution, in-vitro antitubercular activity, aerodynamic characters, surface morphology, and thermal behavior. The optimized formulation of rifampicin-loaded freeze-dried liposome and free rifampicin was subjected for the in-vivo drug disposition study in Wister rat model by intra-tracheal instillation in comparison with an oral route of administration. Results: The results of pharmacokinetic study for both free drug and the formulation suggested that liposomes released the drug in a controlled manner for a longer period of time. The enhanced efficiency of drug incorporated into liposomes suggested that the delivery of encapsulated drugs to macrophages was more rapid than that of free drug. Conclusion: Therefore, the pharmacokinetic and drug disposition studies provided a sound basis for predicting the successful treatment for tuberculosis. PMID:26180381

  9. Drug delivery strategies to enhance the permeability of the blood–brain barrier for treatment of glioma

    PubMed Central

    Zhang, Fang; Xu, Chun-Lei; Liu, Chun-Mei

    2015-01-01

    Gliomas are amongst the most insidious and destructive types of brain cancer and are associated with a poor prognosis, frequent recurrences, and extremely high lethality despite combination treatment of surgery, radiotherapy, and chemotherapy. The existence of the blood–brain barrier (BBB) restricts the delivery of therapeutic molecules into the brain and offers the clinical efficacy of many pharmaceuticals that have been demonstrated to be effective for other kinds of tumors. This challenge emphasizes the need to be able to deliver drugs effectively across the BBB to reach the brain parenchyma. Enhancement of the permeability of the BBB and being able to transport drugs across it has been shown to be a promising strategy to improve drug absorption and treatment efficacy. This review highlights the innovative technologies that have been introduced to enhance the permeability of the BBB and to obtain an optimal distribution and concentration of drugs in the brain to treat gliomas, such as nanotechniques, hyperthermia techniques, receptor-mediated transport, cell-penetrating peptides, and cell-mediated delivery. PMID:25926719

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

    PubMed Central

    2014-01-01

    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 < 0.001) of women with first visit during the third trimester received only one dose, meanwhile, those who had an early first ANC attendance were more likely (OR = 0.4; 95% CI = 0.2 - 0.7) to receive two or more doses. Microscopic parasitaemia at delivery was frequent (P = 0.007) among women who enrolled in the third trimester and had