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Sample records for accurate treatment delivery

  1. How Accurate Is the Dating of Scheduled 39-Week Deliveries?

    PubMed

    Guseh, Stephanie H; Little, Sarah E; Zera, Chloe A; Robinson, Julian N

    2016-03-01

    Objective We assessed the impact of a policy preventing scheduled repeat cesarean deliveries at less than 39 weeks, accounting for potential inaccuracies in pregnancy dating. Study Design We analyzed a cohort of repeat cesarean deliveries before and after the policy change and used chi-square testing to compare the proportion of deliveries at less than 39 weeks. We assessed whether the reduction in early-term deliveries was different if the gestational age was based on the documented estimated date of delivery (EDD) as compared with best obstetric dating. Results Our cohort consisted of 213 women; 112 before the policy change and 101 after. Using the EDD assigned at delivery, there was a 12.1% absolute decrease in scheduled deliveries at less than 39 weeks (25.0-12.9%; p = 0.025). However, using the EDD by best obstetric dating, there was no significant change (32.1-25.7%; p = 0.305). Of the 85 discrepant EDDs, providers were more likely to assign an earlier EDD (63.5%; p = 0.013). Conclusion Our institution's policy change led to a 12.1% absolute reduction in documented, scheduled early-term deliveries, however only a 6.4% absolute decline using best obstetric dating. Policy initiatives to reduce early-term deliveries should consider the source and accuracy of the assigned pregnancy dating. PMID:26461926

  2. Design of microprobe for accurate thermal treatment of tumor.

    PubMed

    Chen, Chao; Zhang, Aili; Cai, Zhanghao; Sun, Jianqi; Xu, Lisa X

    2011-01-01

    Thermal treatment has become an alternative modality for cancer treatment. Low temperature freezing and high temperature heating kill tumor cells effectively through direct and indirect injuries by biochemical and physical stresses. Hyperthermia at a mildly elevated temperature has also been reported to induce biochemical alternations to kill tumor cells and to stimulate immunological response to prevent metastasis. The comprehensive multi-scale biological responses to different thermal history experienced demand an accurate temperature control of the thermal system used for such a treatment. A thermal system was built in our lab utilizing RF heating and liquid nitrogen cooling through a needle probe. In practice, difficulties involved in temperature measurement for in vivo monitoring and control of thermal input through two-phase LN2 flow inside the probe compromise the treatment outcome. To ensure an accurate temperature control, a new model was developed to study the dynamic freezing capacity of the cryo-probe by accounting for the probe shape and dimensions. The model was validated by experiments and used to predict the freezing processes under different conditions. Numerical simulation results showed that combined with RF heating, the system could be used to perform different treatment protocols with an accurate temperature control. PMID:21766157

  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 attributed to phantom setup errors due to the slightly deformable and flexible phantom extremities. The estimated site-specific safety buffer distance with 0.001% probability of collision for (gantry-to-couch, gantry-to-phantom) was (1.23 cm, 3.35 cm), (1.01 cm, 3.99 cm), and (2.19 cm, 5.73 cm) for treatment to the head, lung, and prostate, respectively. Automated delivery to all three treatment sites was completed in 15 min and collision free using a digital Linac. Conclusions: An individualized collision prediction model for the purpose of noncoplanar beam delivery was developed and verified. With the model, the study has demonstrated the feasibility of predicting deliverable beams for an individual patient and then guiding fully automated noncoplanar treatment delivery. This work motivates development of clinical workflows and quality assurance procedures to allow more extensive use and automation of noncoplanar beam geometries.

  4. 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 review.

  5. Pulmonary drug delivery systems for tuberculosis treatment.

    PubMed

    Pham, Dinh-Duy; Fattal, Elias; Tsapis, Nicolas

    2015-01-30

    Tuberculosis (TB) remains a major global health problem as it is the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus (HIV). Conventional treatments fail either because of poor patient compliance to the drug regimen or due to the emergence of multidrug-resistant tuberculosis. The aim of this review is to give an update on the information available on tuberculosis, its pathogenesis and current antitubercular chemotherapies. Direct lung delivery of anti-TB drugs using pulmonary delivery systems is then reviewed since it appears as an interesting strategy to improve first and second line drugs. A particular focus is place on research performed on inhalable dry powder formulations of antitubercular drugs to target alveolar macrophages where the bacteria develop. Numerous studies show that anti-TB drugs can be incorporated into liposomes, microparticles or nanoparticles which can be delivered as dry powders to the deep lungs for instantaneous, targeted and/or controlled release. Treatments of infected animals show a significant reduction of the number of viable bacteria as well as a decrease in tissue damage. These new formulations appear as interesting alternatives to deliver directly drugs to the lungs and favor efficient TB treatment. PMID:25499020

  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. A novel sulfur mustard (HD) vapor inhalation exposure system for accurate inhaled dose delivery

    PubMed Central

    Perry, Mark R.; Benson, Eric M.; Kohne, Jonathon W.; Plahovinsak, Jennifer L.; Babin, Michael C.; Platoff, Gennady E.; Yeung, David T.

    2014-01-01

    Introduction A custom designed HD exposure system was used to deliver controlled inhaled doses to an animal model through an endotracheal tube. Methods Target HD vapor challenges were generated by a temperature controlled bubbler/aerosol trap, while concentration was monitored near real-time by gas chromatography. Animal breathing parameters were monitored real-time by an in-line pneumotach, pressure transducer, and Buxco pulmonary analysis computer/software. For each exposure, the challenge atmosphere was allowed to stabilize at the desired concentration while the anesthetized animal was provided humidity controlled clean air. Once the target concentration was achieved and stable, a portion of the challenge atmosphere was drawn past the endotracheal tube, where the animal inhaled the exposure ad libitum. During the exposure, HD vapor concentration and animal weight were used to calculate the needed inhaled volume to achieve the target inhaled dose (μg/kg). The exposures were halted when the inhaled volume was achieved. Results The exposure system successfully controlled HD concentrations from 22.2 to 278 mg/m3 and accurately delivered inhaled doses between 49.3 and 1120 μg/kg with actual administered doses being within 4% of the target level. Discussion This exposure system administers specific HD inhaled doses to evaluate physiological effects and for evaluation of potential medical countermeasure treatments. PMID:25291290

  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. 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...

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

    PubMed

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

    2005-11-01

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

  11. 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.

  12. 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

  13. 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

  14. Enhanced skin delivery of vismodegib by microneedle treatment.

    PubMed

    Nguyen, Hiep X; Banga, Ajay K

    2015-08-01

    The present study investigated the effects of microneedle treatment (maltose microneedles, Admin Pen™ 1200, and Admin Pen™ 1500) on in vitro transdermal delivery of vismodegib with different needle lengths, skin equilibration times, and microneedle insertion durations. The influence of microneedle treatment on the dimensions of microchannels (dye binding, calcein imaging, histology, and confocal microscopy studies), transepidermal water loss, and skin permeability of vismodegib was also evaluated. Skin viscoelasticity was assessed using a rheometer, and microneedle geometry was characterized by scanning electron microscopy. Permeation studies of vismodegib through dermatomed porcine ear skin were conducted using vertical Franz diffusion cells. Skin irritation potential of vismodegib formulation was assessed using an in vitro reconstructed human epidermis model. Results of the in vitro permeation studies revealed significant enhancement in permeation of vismodegib through microneedle-treated skin. As the needle length increased from 500 to 1100 and 1400 μm, drug delivery increased from 14.50 ± 2.35 to 32.38 ± 3.33 and 74.40 ± 15.86 μg/cm(2), respectively. Positive correlation between drug permeability and microneedle treatment duration was observed. The equilibration time was also found to affect the delivery of vismodegib. Thus, changes in microneedle length, equilibration time, and duration of treatment altered transdermal delivery of vismodegib. PMID:26069156

  15. 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

  16. 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

  17. Convection-enhanced delivery: targeted toxin treatment of malignant glioma.

    PubMed

    Hall, Walter A; Sherr, Gregory T

    2006-01-01

    Historically, malignant gliomas are perhaps the most difficult intracranial neoplasms to treat. Surgery, radiation therapy, and traditional chemotherapy have not been able to significantly alter the course of this disease. By definition, these tumors are located in the protected space of the cranial vault, where the blood-brain barrier prevents most therapies from gaining access. Because of the difficulty in treating this disease, new, innovative treatments and alternative delivery techniques for those therapies are needed. Targeted toxins are fusion proteins that represent a novel medical treatment for these cancers that is under development. However, the efficacy of these agents is dependent on the method of delivery to the tumor. The administration of targeted toxins requires image-guided placement of catheters, either within the tumor or into the adjacent infiltrated brain, and positive pressure infusion. The term that has been applied to this microinfusion technique is convection-enhanced delivery (CED). This infusion method was first attempted via direct intratumoral infusion in nude mouse flank tumor models of human malignant glioma. After significant development of this delivery technique in animal models, the successful demonstration of in vivo efficacy of targeted toxins in Phase I and II clinical trials was reported. Currently, ongoing targeted toxin trials are being conducted at academic health centers to define the best clinical practice for CED. This work involves refining the details of delivery such as infusion rate, duration of treatment, and drug dosing. The early results of CED of targeted toxins supports their continued investigation, as few other treatment modalities have produced durable results in the fight against gliomas. PMID:16709015

  18. 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

  19. Convection-enhanced delivery for the treatment of glioblastoma

    PubMed Central

    Vogelbaum, Michael A.; Aghi, Manish K.

    2015-01-01

    Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low–positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique. PMID:25746090

  20. 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

  1. 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

  2. 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.; Department of Physics and Astronomy, University of Manitoba, Winnipeg, Manitoba R3T 2N2; Department of Radiology, University of Manitoba, Winnipeg, Manitoba R3T 2N2 ; 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.

  3. 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.

  4. Drug and gene co-delivery systems for cancer treatment.

    PubMed

    Yang, Zhe; Gao, Di; Cao, Zhong; Zhang, Chao; Cheng, Du; Liu, Jie; Shuai, Xintao

    2015-07-01

    Cancer remains a major killer and a leading cause of death in the world; thus, a growing number of new treatments have been focused on cancer therapy over the past few decades. Chemotherapy, which is thought to be a powerful strategy for cancer treatment, has been widely used in clinical therapy in recent years. However, due to the complexity of cancer, a single therapeutic approach is insufficient for the suppression of cancer growth and migration. Therefore, increasing attention has been paid to the use of smart multifunctional carriers and combinatorially delivers chemotherapeutic drugs and functional genes in order to maximize therapeutic efficiency. Combination therapy using selected drugs and genes can not only overcome multidrug resistance and inhibit the cellular anti-apoptotic process but also achieve a synergistic therapeutic effect. Because multifunctional nanocarriers are important for achieving these goals, this review will illustrate and discuss some advanced biomaterial nanocarriers for co-delivering therapeutic genes and drugs, including multifunctional micelles, liposomes, polymeric conjugates and inorganic nanoparticles. In addition, the challenges and future perspectives for co-delivery systems, containing therapeutic drugs and genes to achieve better therapeutic effects for cancer treatment will be discussed. PMID:26221938

  5. 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.

  6. Accurate semi-implicit treatment of the Hall effect in magnetohydrodynamic computations

    SciTech Connect

    Harned, D.S.; Mikic, Z. )

    1989-07-01

    A semi-implicit operator is derived for the Hall term that, when implemented in the MHD equations, allows time steps comparable to those normally used in semi-implicit MHD computations. The operator is fourth order in the direction of the magnetic field and is most accurate when used in a split time step algorithm. The effects of the semi-implicit treatment on linear waves in a cylinder are shown both through a detailed analysis and numerical tests. The effectiveness of the algorithm is also demonstrated with a nonlinear computation of a tokamak tearing instability. {copyright} 1989 Academic Press, Inc.

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

    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.

  8. 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

  9. Iontophoretic drug delivery for the treatment of scars.

    PubMed

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

    2014-06-01

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

  10. 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.

  11. Functional Polymers of Gene Delivery for Treatment of Myocardial Infarct

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. Towards an accurate treatment of σ∗ ← σ transitions: Moving onto N6.-

    NASA Astrophysics Data System (ADS)

    Dumont, Élise; Ferré, Nicolas; Monari, Antonio

    2013-08-01

    Dimeric σ∗ radical anions are ubiquitous, and their formation, spectroscopy and outcome can often be elucidated by density functional theory. But for shorter interfragment distances, three-electron two-center systems can be reluctant to a single-determinant description, such as the hexanitrogen radical anion. For N6.-, we show that multireference configuration interactions calculations are required to recover its characteristic electronic excitation energy, while TDDFT fails even with modern exchange-correlation functionals. The effects of vibronic couplings on the absorption spectrum are delineated based on a full quantum mechanical dynamical treatment; this study opens the door towards an accurate description of the subtle solvatochromism of hemi-bonded systems.

  14. Ultrasonic-Activated Micellar Drug Delivery for Cancer Treatment

    PubMed Central

    Husseini, Ghaleb A.; Pitt, William G.

    2008-01-01

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

  15. 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.

  16. 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

  17. 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 using these schemes is especially sensitive to the type of equation treatment at the singularity axis. The objective of this work is to develop a generally applicable numerical method for treating the singularities present at the polar axis, which is particularly suitable for highly accurate finite-differences schemes (e.g., Pade schemes) on non-staggered grids. The main idea is to reinterpret the regularity conditions developed in the context of pseudo-spectral methods. A set of exact equations at the singularity axis is derived using the appropriate series expansions for the variables in the original set of equations. The present treatment of the equations preserves the same level of accuracy as for the interior scheme. We also want to point out the wider utility of the method, proposed here in the context of compressible flow equations, as its extension for incompressible flows or for any other set of equations that are solved on a non-staggered mesh in cylindrical coordinates with finite-differences schemes of various level of accuracy is straightforward. The robustness and accuracy of the proposed technique is assessed by comparing results from simulations of laminar forced-jets and turbulent compressible jets using LES with similar calculations in which the equations are solved in Cartesian coordinates at the polar axis, or in which the singularity is removed by employing a staggered mesh in the radial direction without a mesh point at r = 0.

  18. 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 the proposed prediction algorithm is sufficient to support patient treatment appointment scheduling. This developed software tool is currently applied in use on a daily basis in our clinic, and could also be used as an important indicator for treatment plan complexity. PMID:27074472

  19. 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, we defined an acceptable pass rate of >90% of percentage pixels with γ <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system.

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

    PubMed

    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, we defined an acceptable pass rate of >90% of percentage pixels with γ <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system. PMID:23640066

  1. 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

  2. Energy Delivery Systems for Treatment of Benign Prostatic Hyperplasia

    PubMed Central

    2006-01-01

    Executive Summary Objective The Ontario Health Technology Advisory Committee asked the Medical Advisory Secretariat (MAS) to conduct a health technology assessment on energy delivery systems for the treatment of benign prostatic hyperplasia (BPH). Clinical Need: Target Population and Condition BPH is a noncancerous enlargement of the prostate gland and the most common benign tumour in aging men. (1) It is the most common cause of lower urinary tract symptoms (LUTS) and bladder outlet obstruction (BOO) and is an important cause of diminished quality of life among aging men. (2) The primary goal in the management of BPH for most patients is a subjective improvement in urinary symptoms and quality of life. Until the 1930s, open prostatectomy, though invasive, was the most effective form of surgical treatment for BPH. Today, the benchmark surgical treatment for BPH is transurethral resection of the prostate (TURP), which produces significant changes of all subjective and objective outcome parameters. Complications after TURP include hemorrhage during or after the procedure, which often necessitates blood transfusion; transurethral resection (TUR) syndrome; urinary incontinence; bladder neck stricture; and sexual dysfunction. A retrospective review of 4,031 TURP procedures performed by one surgeon between 1979 and 2003 showed that the incidence of complications was 2.4% for blood transfusion, 0.3% for TUR syndrome, 1.5% for hemostatic procedures, 2.8% for bladder neck contracture, and 1% for urinary stricture. However, the incidence of blood transfusion and TUR syndrome decreased as the surgeon’s skills improved. During the 1990s, a variety of endoscopic techniques using a range of energy sources have been developed as alternative treatments for BPH. These techniques include the use of light amplification by stimulated emission of radiation (laser), radiofrequency, microwave, and ultrasound, to heat prostate tissue and cause coagulation or vaporization. In addition, new electrosurgical techniques that use higher amounts of energy to cut, coagulate, and vaporize prostatic tissue have entered the market as competitors to TURP. The driving force behind these new treatment modalities is the potential of producing good hemostasis, thereby reducing catheterization time and length of hospital stay. Some have the potential to be used in an office environment and performed under local anesthesia. Therefore, these new procedures have the potential to rival TURP if their effectiveness is proven over the long term. The Technology Being Reviewed The following energy-based techniques were considered for assessment: transurethral electrovaporization of the prostate (TUVP) transurethral electrovapor resection of the prostate (TUVRP) transurethral electrovaporization of the prostate using bipolar energy (plasmakinetic vaporization of the prostate [PKVP]) visual laser ablation of the prostate (VLAP) transurethral ultrasound guided laser incision prostatectomy (TULIP) contact laser vaporization of the prostate (CLV) interstitial laser coagulation (ILC) holmium laser resection of the prostate (HoLRP) holmium laser enucleation of the prostate (HoLEP) holmium laser ablation of the prostate (HoLAP) potassium titanyl phosphate (KTP) laser transurethral microwave thermotherapy (TUMT) transurethral needle ablation (TUNA) Review Strategy A search of electronic databases (OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library, and the International Agency for Health Technology Assessment [INAHTA] database) was undertaken to identify evidence published from January 1, 2000 to June 21, 2006. The search was limited to English-language articles and human studies. The literature search identified 284 citations, of which 38 randomized controlled trials (RCTs) met the inclusion criteria. Since the application of high-power (80 W) KTP laser (photoselective vaporization of the prostate [PVP]) has been supported in the United States and has resulted in a rapid diffusion of this technology in the absence of any RCTs, the MAS decided that any comparative studies on PVP should be identified and evaluated. Hence, the literature was searched and one prospective cohort study (3) was identified but evaluated separately. Findings of Literature Review and Analysis Meta-analysis of the results of RCTs shows that monopolar electrovaporization is as clinically effective as TURP for the relief of urinary symptoms caused by BPH (based on 5-year follow-up data). Meta-analysis of the results of RCTs shows that bipolar electrovaporization (PKVP) is clinically as effective as TURP for the relief of urinary symptoms caused by BPH (based on 1-year follow-up data). Two of the three RCTs on VLAP have shown that patients undergoing VLAP had a significantly lesser improvement in urinary symptom scores compared with patients undergoing TURP. RCTs showed that the time to catheter removal was significantly longer in patients undergoing VLAP compared with patients undergoing TURP. Meta-analysis of the rate of reoperation showed that patients undergoing VLAP had a significantly higher rate of reoperation compared with patients undergoing TURP. Meta-analysis showed that patients undergoing CLV had a significantly lesser improvement in urinary symptom scores compared with TURP at 2 years and at 3 or more years of follow-up. Two RCTs with 6-month and 2-year follow-up showed similar improvement in symptom scores for ILC and TURP. Time to catheter removal was significantly longer in patients undergoing ILC compared with patients undergoing TURP. The results of RCTs on HoLEP with 1-year follow-up showed excellent clinical outcomes with regard to the urinary symptom score and peak urinary flow. Meta-analysis showed that at 1-year follow-up, patients undergoing HoLEP had a significantly greater improvement in urinary symptom scores and peak flow rate compared with patients undergoing TURP. Procedural time is significantly longer in HoLEP compared with TURP. The results of one RCT with 4-year follow-up showed that HoLRP and TURP provided equivalent improvement in urinary symptom scores. The results of one RCT with 1-year follow-up showed that patients undergoing KTP had a lesser improvement in urinary symptom scores than did patients undergoing TURP. However, the results were not significant at longer-term follow-up periods. Two RCTs that provided 3-year follow-up data reported that patients undergoing TUMT had a significantly lesser improvement in symptom score compared with patients undergoing TURP. RCTs reported a longer duration of catheterization for TUMT compared with TURP (P values are not reported). The results of a large RCT with 5-year follow-up showed a significantly lesser improvement in symptom scores in patients undergoing TUNA compared with patients undergoing TURP. Meta-analysis of the rate of reoperation showed that patients undergoing TUNA had a significantly higher rate of reoperation compared with patients undergoing TURP. Based on the results of RCTs, TURP is associated with a 0.5% risk of TUR syndrome, while no cases of TUR syndrome have been reported in patients undergoing monopolar or bipolar electrovaporization, laser-based procedures, TUMT, or TUNA. Based on the results of RCTs, the rate of blood transfusion ranges from 0% to 8.3% in patients undergoing TURP. The rate is about 1.7% in monopolar electrovaporization, 1.4% in bipolar electrovaporization, and 0.4% in the VLAP procedure. No patients undergoing CLV, ILC, HoLEP, HoLRP, KTP, TUMT, and TUNA required blood transfusion. The mean length of hospital stay is between 2 and 5 days for patients undergoing TURP, about 3 days for electrovaporization, about 2 to 4 days for Nd:YAG laser procedures, and about 1 to 2 days for holmium laser procedures. TUMT and TUNA can each be performed as a day procedure in an outpatient setting (0.5 and 1 day respectively). Based on a prospective cohort study, PVP is clinically as effective as TURP for the relief of urinary symptoms caused by BPH (based on 6-month follow-up data). Time to catheter removal was significantly shorter in patients undergoing PVP than in those undergoing TURP. Operating room time was significantly longer in PVP than in TURP. PVP has the potential to reduce health care expenses due to shorter hospital stays. Economic Analysis In the three most recent fiscal years (FY) reported, an average of approximately 5,000 TURP procedures per year were performed in Ontario. From FY 2002 to FY 2004, the total number of surgical interventions decreased by approximately 500 procedures. During this time, the increase in costs of drugs to the government was estimated at approximately $10 million (Cdn); however, there was a concurrent decrease in costs due to a decline in the total number of surgical procedures, estimated at approximately $1.9 million (Cdn). From FY 2002 to FY 2004, the increase in costs associated with the increase in utilization of drugs for the treatment of BPH translates into $353 (Cdn) per patient while the cost savings associated with a decrease in the total number of surgical procedures translates into a savings of $3,906 (Cdn) per patient. The following table summarizes the change in the current budget, depending on various estimates of the total percentage of the 5,000 TURP procedures that might be replaced by other energy-based interventions for the treatment of BPH in the future. Executive Summary Table 1: Budget Impact With Various Estimates of the Percentage of TURP Procedures Captured by Energy-based Interventions for the Treatment of BPH Technology Cost perprocedure, $ Budget Impact of 25% diffusion, $M Budget Impact of 50% diffusion, $M Budget Impact of 75% diffusion, $M Budget Impact of 100% diffusion, $M Incremental Budget Impact, $M TURP 3,887 19.4 Bipolar Electrovaporization 4,011 19.6 19.7 19.9 20.0 0.6 Monopolar Electrovaporization 4,130 19.7 20.0 20.3 20.6 1.2 TUMT 1,529 16.5 13.5 10.6 7.6 (11.8)  TUNA 4,804 20.6 21.7 22.9 24.0 4.6 PVP 1,184 16.0 12.7 9.3 5.9 (13.5)   Holmium Laser 3,892 19.4 19.4 19.4 19.4 0.02 VLAP Nd:YAG 4,663 20.4 21.4 22.3 23.3 3.9 CLAP Nd:YAG 4,615 20.3 21.2 22.4 23.0 3.6 * All costs are in Canadian currency. Parentheses indicative of cost reduction. PMID:23074487

  3. 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.

  4. 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

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

    PubMed Central

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

    2009-01-01

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

  6. 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

  7. 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

  8. 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.

  9. 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 physicist weekly chart review. PMID:27167269

  10. 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 factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.

  11. 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

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

    PubMed

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

    2013-12-10

    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

  13. 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

  14. 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.

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

    PubMed

    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

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

    PubMed Central

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

    2014-01-01

    Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source. PMID:25349381

  17. 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

  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. Psychotherapist effects in meta-analyses: How accurate are treatment effects?

    PubMed

    Owen, Jesse; Drinane, Joanna M; Idigo, K Chinwe; Valentine, Jeffrey C

    2015-09-01

    Psychotherapists are known to vary in their effectiveness with their clients, in randomized clinical trials as well as naturally occurring treatment settings. The fact that therapists matter has 2 effects in psychotherapy studies. First, if therapists are not randomly assigned to modalities (which is rare) this may bias the estimation of the treatment effects, as the modalities may have therapists of differing skill. In addition, if the data are analyzed at the client level (which is virtually always the case) then the standard errors for the effect sizes will be biased due to a violation of the assumption of independence. Thus, the conclusions of many meta-analyses may not reflect true estimates of treatment differences. We reexamined 20 treatment effects selected from 17 meta-analyses. We focused on meta-analyses that found statistically significant differences between treatments for a variety of disorders by correcting the treatment effects according to the variability in outcomes known to be associated with psychotherapists. The results demonstrated that after adjusting the results based on most small estimates of therapist effects, ∼80% of the reported treatment effects would still be statistically significant. However, at larger estimates, only 20% of the treatment effects would still be statistically significant after controlling for therapist effects. Although some meta-analyses were consistent in their estimates for treatment differences, the degree of certainty in the results was considerably reduced after considering therapist effects. Practice implications for understanding treatment effects, namely, therapist effects, in meta-analyses and original studies are provided. PMID:26301423

  20. Improving Tobacco Dependence Treatment Delivery: Medical Student Training and Assessment.

    PubMed

    Folan, Patricia A; Juster, Harlan R; Lennon, Susan E; Briest, Patricia J; Gero, C Beth

    2015-08-01

    Tobacco dependence is a chronic condition, with cigarette smoking considered the leading cause of preventable death, disease, and disability in the U.S. Currently, the U.S. adult smoking rate is 17.8%. National surveys reveal that approximately half of all smokers who have been treated by a healthcare provider in the last 12 months received Public Health Service-recommended guideline-concordant tobacco dependence treatment. Although smoking prevalence has been declining, several disparate groups continue to smoke at rates significantly higher than the national average, including those with low income, low educational attainment, or mental health disorders. To address these disparities and more effectively address tobacco use, provision of guideline-concordant tobacco dependence treatment within the healthcare system must improve. We discuss changes to the medical licensing examination that may result in enhanced tobacco dependence treatment education and skills training for students in medical school. PMID:26091923

  1. 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

  2. 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.

  3. 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

  4. What Is the Most Accurate Method for the Treatment of Diminutive Colonic Polyps?

    PubMed Central

    Aslan, Fatih; Ceki, Cem; Camci, Mehmet; Alper, Emrah; Ekinci, Nese; Akpinar, Zehra; Alpek, Serkan; Arabul, Mahmut; Unsal, Belkis

    2015-01-01

    Abstract Different methods such as standard, hot, and jumbo forceps are used in endoscopic treatment of diminutive colon polyps. In the current study, it was aimed to compare efficacy and safety of standard and jumbo forceps polypectomy methods in treatment of diminutive colon polyps of ?5?mm. Polyps with ?5 mm which were excised during colonoscopy by using standard or jumbo forceps were evaluated. Standard and jumbo forceps polypectomy methods were randomly performed in 212 consecutive patients with diminutive colorectal polyp. One-bite polypectomy and complete resection rates were also determined among polypectomy methods. Results of 161 standard forceps polypectomy and 102 jumbo forceps polypectomy were retrospectively evaluated. Both one-bite polypectomy and complete resection rates were significantly higher in the jumbo forceps polypectomy group than the standard forceps polypectomy group (P?treatment methods may be employed in treatment of diminutive colon polyps with ?5?mm. However, jumbo forceps polypectomy is a more effective treatment method in 4- to 5-mm polyps with high one-bite polypectomy and complete resection rate. PMID:25881835

  5. 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

  6. Nanostructured platforms for the sustained and local delivery of antibiotics in the treatment of osteomyelitis.

    PubMed

    Uskokovic, 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

  7. 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

  8. Topical delivery of drugs for the effective treatment of fungal infections of skin.

    PubMed

    Akhtar, Nida; Verma, Anurag; Pathak, Kamla

    2015-01-01

    The prevalence of fungal infections of skin has increased rapidly, affecting approximately 40 million people across the globe. A wide variety of antifungal drugs has been utilized in the effective management of numerous dermatological infections. Topical treatment of fungal infections has proved to be quite advantageous due to various factors like targeting the site of infection, minimizing systemic side effects, enhanced efficacy of treatment, and improved patient compliance. In spite the fact that these agents are therapeutically active on topical application, these have restricted drug delivery across the skin resulting in insufficient therapeutic index and may exert local as well as systemic side effects. The accomplishment of topical drug delivery needs to pacify two anomalous aspects, first the barrier nature of stratum corneum, and second, deposition of drug within the skin should be ideally achieved with limited percutaneous absorption. Thus, to facilitate the delivery of antifungal drugs and improve the treatment aspects, various novel delivery carriers have been developed. This article attempts to provide an in-depth knowledge of nanoparticulate and vesicular carriers. This article focuses on the different aspects of fungal infections and their effective treatment with antifungal drugs. Efficacy of various carrier systems (nanoparticulate and vesicular carriers) in delivering antifungal drugs topically has also been discussed. Besides, compiling various research reports, this article also includes formulation considerations inclusive of regulatory aspects of excipients used, the mechanisms of penetration, and patents reported. PMID:25925110

  9. A biotin-guided fluorescent-peptide drug delivery system for cancer treatment.

    PubMed

    Kim, Taeyoung; Jeon, Hyun Mi; Le, Hoa Thi; Kim, Tae Woo; Kang, Chulhun; Kim, Jong Seung

    2014-07-21

    Herein, we present a fluorescent-peptide drug delivery system composed of biotin-naphthalimide-HJ inhibitor peptide2, prodrug 1. Treatment of 1 to biotin receptor-positive HepG2 cells, which are resistant to high concentrations of the HJ inhibitor peptide2, decreased cell viability and increased intracellular fluorescence. PMID:24898048

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Treatment Strategies for Self-Injurious Behavior in a Large Service-Delivery Network.

    ERIC Educational Resources Information Center

    Altmeyer, Bernd K.; And Others

    1987-01-01

    The scope of psychoactive drug use within a statewide (Texas) institutional service delivery network was examined, with a focus on its role in the treatment of self-injurious behavior and other aberrant behaviors in the retarded. Insufficient use of behavioral technology and overuse of physical and chemical restraints were indicated. (Author/DB)

  12. 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

  13. 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

  14. 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

  15. Flattening filter-free linac improves treatment delivery efficiency in stereotactic body radiation therapy.

    PubMed

    Prendergast, Brendan M; Fiveash, John B; Popple, Richard A; Clark, Grant M; Thomas, Evan M; Minnich, Douglas J; Jacob, Rojymon; Spencer, Sharon A; Bonner, James A; Dobelbower, Michael C

    2013-01-01

    Stereotactic body radiation therapy (SBRT) employs precision target tracking and image-guidance techniques to deliver ablative doses of radiation to localized malignancies; however, treatment with conventional photon beams requires lengthy treatment and immobilization times. The use of flattening filter-free (FFF) beams operating at higher dose rates can shorten beam-on time, and we hypothesize that it will shorten overall treatment delivery time. A total of 111 lung and liver SBRT cases treated at our institution from July 2008 to July 2011 were reviewed and 99 cases with complete data were identified. Treatment delivery times for cases treated with a FFF linac versus a conventional dose rate linac were compared. The frequency and type of intrafraction image guidance was also collected and compared between groups. Three hundred and ninety-one individual SBRT fractions from 99 treatment plans were examined; 36 plans were treated with a FFF linac. In the FFF cohort, the mean ( standard deviation) treatment time (time elapsed from beam-on until treatment end) and patient's immobilization time (time from first alignment image until treatment end) was 11.44 ( 6.3) and 21.08 ( 6.8) minutes compared to 32.94 ( 14.8) and 47.05 ( 17.6) minutes for the conventional cohort (p < 0.01 for all values). Intrafraction-computed tomography (CT) was used more often in the conventional cohort (84% vs. 25%; p < 0.05), but use of orthogonal X-ray imaging remained the same (16% vs. 19%). For lung and liver SBRT, a FFF linac reduces treatment and immobilization time by more than 50% compared to a conventional linac. In addition, treatment with a FFF linac is associated with less physician-ordered image guidance, which contributes to further improvement in treatment delivery efficiency. PMID:23652246

  16. 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

  17. Office laser delivery systems for the treatment of hypertrophic turbinates

    NASA Astrophysics Data System (ADS)

    Krespi, Y. P.; Slatkine, Michael

    1995-05-01

    We present two different methods to treat hypertrophic turbinates in an office environment: (a) with the aid of 1 mm thin hollow waveguides transmitting a CO2 laser beam to produce char-free ablation of turbinate mucosa, and (b) with the aid of a 800 micron thin optical fiber transmitting low power Nd:YAG laser radiation to interstitially coagulate and shrink submucosal tissue. Char-free ablation of mucusal tissue: An office CO2 laser regularly used for LAUP in the treatment of snoring problems is operated in the Superpulse mode (peak power 350 W) at 8 W average power. The optical beam is coupled to angled and straight hollow waveguides. Ablation of inferior turbinates is performed within a few minutes under topical or local anesthesia. No post operative packing is required and the patient can return to normal activities. Healing is fast due to the highly controlled superficial thermal damage. Interstitial coagulation of inferior turbinates: Submucosal coagulation of tissue is attained with a flat 800 (mu) fiber longitudinally pushed and pulled while operating an Nd:YAG laser at 8 W power level. A 4 - 6 mm thin coagulated and shrunken volume of cylindrical shape is being produced with no damage to bones or mucosa. The procedure is fast and performed under local anesthesia. An analysis of both surgical techniques and clinical results with over 100 patients will be presented.

  18. 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

  19. 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

  20. 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

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

    PubMed

    Wark, Stuart; Hussain, Rafat; Parmenter, Trevor

    2014-12-01

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

  2. Accurate Diagnosis as a Prognostic Factor in Intrauterine Insemination Treatment of Infertile Saudi Patients

    PubMed Central

    Isa, Ahmed Mostafa; Abu-Rafea, Basim; Alasiri, Saleh Ahmed; Al-Mutawa, Johara; Binsaleh, Saleh; Al-Saif, Sameera; Al-Saqer, Aisha

    2014-01-01

    Background The study meant to define the prognostic factors that help in prescribing intrauterine insemination (IUI) for infertility treatment which remains an area of continuous improvements. Methods The diagnostic indications of a cohort of IUI-treated patients and their corresponding pregnancy rates (PRs) were randomly and prospectively studied among Saudi cohort of 303 patients for a period of 20 months. The indications of IUI cases were statistically analyzed for those eligible patients over a period of twenty months (January 2010 till August 2011), and the PR that corresponded to each group was investigated as well. P-value less than 0.05 was considered significant. Results The highest PR, 18.87%, of the polycystic ovarian syndrome (PCOS)-only diagnosed patients, was significantly higher than the average PR of all other indications combined, 7.22%, (p = 0.011, compared to all other groups combined). The second highest PR, 14.0%, of the tubal factor (TF)-only indication, was double the PR average of all other indications combined, though it did not reach significance. However, PCOS and TF accompanied by other indications caused the PR to drop to 5.88% and 5.56%, respectively. However, a group of some hormonal-imbalance based indications had the least PR (0.0% to 2.70%). Those indications were elevated serum FSH, hyperprolactinemia, hypogonadotrophy, hypothyroidism and endometriosis. The rest of the indications had an average PR (8.33% to 11.11%). Conclusion There is a reasonable chance of conception after IUI treatment for female factor infertility except in cases with sever hormonal imbalance. The PCOS cases having the best success chances. PMID:25473626

  3. 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. Results: Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system’s ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. Conclusions: The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.

  4. 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

  5. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-10

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

  8. 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.

  9. 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

  10. 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, beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

  11. 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

  12. 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

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

    PubMed

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

    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. D min 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

  14. The feasibility of using Pareto fronts for comparison of treatment planning systems and delivery techniques.

    PubMed

    Ottosson, Rickard O; Engstrom, Per E; Sjöström, David; Behrens, Claus F; Karlsson, Anna; Knöös, Tommy; Ceberg, Crister

    2009-01-01

    Pareto optimality is a concept that formalises the trade-off between a given set of mutually contradicting objectives. A solution is said to be Pareto optimal when it is not possible to improve one objective without deteriorating at least one of the other. A set of Pareto optimal solutions constitute the Pareto front. The Pareto concept applies well to the inverse planning process, which involves inherently contradictory objectives, high and uniform target dose on one hand, and sparing of surrounding tissue and nearby organs at risk (OAR) on the other. Due to the specific characteristics of a treatment planning system (TPS), treatment strategy or delivery technique, Pareto fronts for a given case are likely to differ. The aim of this study was to investigate the feasibility of using Pareto fronts as a comparative tool for TPSs, treatment strategies and delivery techniques. In order to sample Pareto fronts, multiple treatment plans with varying target conformity and dose sparing of OAR were created for a number of prostate and head & neck IMRT cases. The DVHs of each plan were evaluated with respect to target coverage and dose to relevant OAR. Pareto fronts were successfully created for all studied cases. The results did indeed follow the definition of the Pareto concept, i.e. dose sparing of the OAR could not be improved without target coverage being impaired or vice versa. Furthermore, various treatment techniques resulted in distinguished and well separated Pareto fronts. Pareto fronts may be used to evaluate a number of parameters within radiotherapy. Examples are TPS optimization algorithms, the variation between accelerators or delivery techniques and the degradation of a plan during the treatment planning process. The issue of designing a model for unbiased comparison of parameters with such large inherent discrepancies, e.g. different TPSs, is problematic and should be carefully considered. PMID:18752085

  15. 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

    2016-02-23

    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

  16. 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

  17. 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

  18. 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 statistically significant. Conclusions: The proposed algorithm eliminates the need for any population based model parameters in monoscopic image guided radiotherapy and allows accurate and real-time 3D tumor localization on current standard LINACs with a single x-ray imager.

  19. Pregnancy and delivery complications and treatment approach in attention deficit hyperactivity disorder.

    PubMed

    Aktepe, Evrim; Ozkorumak, Evrim; Tanriöver-Kandil, Sema

    2009-01-01

    Pregnancy, delivery complications and treatment approach were evaluated in 153 cases diagnosed with attention deficit hyperactivity disorder in the State Hospital of Antalya in the Child and Adolescent Psychiatry Polyclinic. Most of the cases had been delivered vaginally (74.5%). The most frequent delivery complication was asphyxia/hypoxia (15.6%). The agent most frequently preferred in the treatment regimen was methylphenidate (82.4%), which is a psychostimulant. The other drugs used were risperidone (29.4%), selective serotonin reuptake inhibitors (16.4%) and imipramine (4.6%). The most frequent side effect resulting from methylphenidate use was a decrease in appetite (34.9%). Attention deficit hyperactivity disorder often presents with comorbid disorders; in these cases, nonstimulant agents had to be added to methylphenidate for better treatment outcomes. Use of selective serotonin reuptake inhibitors in combined treatment and in cases with comorbidities is in agreement with the literature. Further studies of combined treatment regimens in attention deficit hyperactivity disorder are needed. PMID:20112604

  20. 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

  1. 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

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

    TOXLINE Toxicology Bibliographic Information

    Knott AM; Corredoira R; Kimberly J

    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.

  3. 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

  4. 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

  5. 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

  6. Furin Targeted Drug Delivery for Treatment of Rhabdomyosarcoma in a Mouse Model

    PubMed Central

    Hajdin, Katarina; D'Alessandro, Valentina; Niggli, Felix K.; Schfer, Beat W.; Bernasconi, Michele

    2010-01-01

    Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Improvement of treatment efficacy and decreased side effects through tumor-targeted drug delivery would be desirable. By panning with a phage-displayed cyclic random peptide library we selected a peptide with strong affinity for RMS in vitro and in vivo. The peptide minimal binding motif Arg-X-(Arg/Lys)(Arg/Lys) identified by alanine-scan, suggested the target receptor to be a proprotein convertase (PC). Expression profiling of all PCs in RMS biopsies and cell lines revealed consistent high expression levels for the membrane-bound furin and PC7. Direct binding of RMS-P3 peptide to furin was demonstrated by affinity chromatography and supported by activity and colocalization studies. Treatment of RMS in mice with doxorubicin coupled to the targeting peptide resulted in a two-fold increase in therapeutic efficacy compared to doxorubicin treatment alone. Our findings indicate surface-furin binding as novel mechanism for therapeutic cell penetration which needs to be further investigated. Furthermore, this work demonstrates that specific targeting of membrane-bound furin in tumors is possible for and suggests that RMS and other tumors might benefit from proprotein convertases targeted drug delivery. PMID:20454619

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

    PubMed Central

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

    2010-01-01

    Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood–brain barrier penetration. Here, we combine 2 methods to increase drug delivery to brain tumors. Focused ultrasound transiently permeabilizes the blood–brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring. PMID:20663792

  8. 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 the 186 IMRT pulses (fields) were found to exceed 50 cGy maximum PTV dose per pulse while the maximum PTV dose per pulse was within 40 cGy for all the VMAT pulses (arcs). However, for VMAT plans, the dosimetric quality of the entire treatment plan was less superior for the breast cases and large irregular targets. The gamma passing rates for both techniques at the 100 MU min-1 dose rate were at least 94.1% (3%/3 mm) and the point dose measurements agreed with the planned values to within 2.2%. The average root mean square error of the leaf position was 0.93 ± 0.83 mm for IMRT and 0.53 ± 0.48 mm for VMAT based on the Dynalog file analysis. The RMS error of the leaf position was nearly identical for the repeated deliveries of the same plans. In general, both techniques are feasible for PLDR treatments. VMAT was more advantageous for PLDR with more uniform target dose per pulse, especially for centrally located tumors. However, for large, irregular and/or peripheral tumors, IMRT could produce more favorable PLDR plans. By taking the biological benefit of PLDR delivery and the dosimetric benefit of IMRT and VMAT, the proposed methods have a great potential for those previously-irradiated recurrent patients.

  9. Sustained dual drug delivery of anti-inhibitory molecules for treatment of spinal cord injury.

    PubMed

    Wilems, Thomas S; Sakiyama-Elbert, Shelly E

    2015-09-10

    Myelin-associated inhibitors (MAIs) and chondroitin sulfate proteoglycans (CSPGs) are major contributors to axon growth inhibition following spinal cord injury and limit functional recovery. The NEP1-40 peptide competitively binds the Nogo receptor and partially blocks inhibition from MAIs, while chondroitinase ABC (ChABC) enzymatically digests CSPGs, which are upregulated at the site of injury. In vitro studies showed that the combination of ChABC and NEP1-40 increased neurite extension compared to either treatment alone when dissociated embryonic dorsal root ganglia were seeded onto inhibitory substrates containing both MAIs and CSPGs. Furthermore, the ability to provide sustained delivery of biologically active ChABC and NEP1-40 from biomaterial scaffolds was achieved by loading ChABC into lipid microtubes and NEP1-40 into poly (lactic-co-glycolic acid) (PLGA) microspheres, obviating the need for invasive intrathecal pumps or catheters. Fibrin scaffolds embedded with the drug delivery systems (PLGA microspheres and lipid microtubes) were capable of releasing active ChABC for up to one week and active NEP1-40 for over two weeks in vitro. In addition, the loaded drug delivery systems in fibrin scaffolds decreased CSPG deposition and development of a glial scar, while also increasing axon growth after spinal cord injury in vivo. Therefore, the sustained, local delivery of ChABC and NEP1-40 within the injured spinal cord may block both myelin and CSPG-associated inhibition and allow for improved axon growth. PMID:26122130

  10. 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 (rCasp3V266ED3, rMcherry red) plasmids were constructed. Membrane anchoring and activity of designed proteins were analyzed in RAW264.7 Mo/Ma and HEK293 cells in vitro. Further, Urokinase (uPA) mediated cleavage and release of rCasp3V266ED3 from engineered cells was tested (Chapter-4). Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments. Final chapter of present report shows evidence for immune-deficient line of pigs as a model for human cancers (Chapter-5)

  11. The relationship of therapeutic alliance and treatment delivery fidelity with treatment retention in a multisite trial of twelve-step facilitation.

    PubMed

    Campbell, Barbara K; Guydish, Joseph; Le, Thao; Wells, Elizabeth A; McCarty, Dennis

    2015-03-01

    This study examined associations of therapeutic alliance and treatment delivery fidelity with treatment retention in Stimulant Abusers to Engage in Twelve-Step (STAGE-12), a community-based trial of 12-Step Facilitation (TSF) conducted within the National Drug Abuse Treatment Clinical Trials Network (CTN). The STAGE-12 trial randomized 234 stimulant abusers enrolled in 10 outpatient drug treatment programs to an eight-session, group and individual TSF intervention. During the study, TSF participants rated therapeutic alliance using the Helping Alliance questionnaire-II. After the study, independent raters evaluated treatment delivery fidelity of all TSF sessions on adherence, competence, and therapist empathy. Poisson regression modeling examined relationships of treatment delivery fidelity and therapeutic alliance with treatment retention (measured by number of sessions attended) for 174 participants with complete fidelity and alliance data. Therapeutic alliance (p = .005) and therapist competence (p = .010) were significantly associated with better treatment retention. Therapist adherence was associated with poorer retention in a nonsignificant trend (p = .061). In conclusion, stronger therapeutic alliance and higher therapist competence in the delivery of a TSF intervention were associated with better treatment retention whereas treatment adherence was not. Training and fidelity monitoring of TSF should focus on general therapist skills and therapeutic alliance development to maximize treatment retention. (PsycINFO Database Record PMID:25134056

  12. Targeted delivery of neurogenin-2 protein in the treatment for cerebral ischemia-reperfusion injury.

    PubMed

    Deng, Bin; Gou, Xingchun; Chen, Hai; Li, Liya; Zhong, Haixing; Xu, Hao; Jiang, Fengliang; Zhao, Zhijing; Wang, Qiang; Xu, Lixian

    2013-11-01

    Neurogenin-2 (Ngn2), as a proneural gene that promotes the survival and differentiation of neural precursor cells, is an attractive candidate for therapy against cerebral ischemia-reperfusion injury. However, the delivery approach limits its clinical application. To deliver Ngn2 protein into the cerebral ischemic region and exert a therapeutic effect on injured neurons after ischemia, we here reported that the fusion protein TAT-LBD-Ngn2 was constructed by fusing a transactivator of transcription (TAT) domain and a laminin-binding domain (LBD) to Ngn2. TAT-LBD-Ngn2 promoted the outgrowth of neuronal neurite, increased the survival rate and alleviated apoptosis of hippocampal neurons exposed to oxygen glucose deprivation invitro. Furthermore, a focal cerebral ischemia model in C57BL/6 mice showed that TAT-LBD-Ngn2 efficiently crossed the blood brain barrier, aggregated in the ischemic zone and was consistently incorporated into neurons. Moreover, TAT-LBD-Ngn2 transduced into brains attenuated neuronal degeneration and apoptosis in the ischemic zone. TAT-LBD-Ngn2 treatment resulted in a reduction of infarct volume that was associated with a parallel improvement in neurological functional outcomes after reperfusion. In conclusion, the targeted delivery of TAT-LBD-Ngn2 into the ischemic zone attenuated cerebral ischemia-reperfusion injury through the inhibition of neuronal degeneration and apoptosis, suggesting that TAT-LBD-Ngn2 is a promising target candidate for the treatment of ischemic stroke. PMID:23942209

  13. 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

  14. Sorafenib and gadolinium co-loaded liposomes for drug delivery and MRI-guided HCC treatment.

    PubMed

    Xiao, Yanan; Liu, Yongjun; Yang, Shaomei; Zhang, Bo; Wang, Tianqi; Jiang, Dandan; Zhang, Jing; Yu, Dexin; Zhang, Na

    2016-05-01

    To improve the poor water solubility of sorafenib and to monitor its distribution and the early feedback effects on its in vivo treatment efficacy in a precise manner, sorafenib (SF) and gadolinium (Gd) co-loaded liposomes (SF/Gd-liposomes) were prepared. The simultaneous imaging and therapy efficacies of the SF/Gd-liposomes were tested. The solubility of SF in SF/Gd-liposomes was significantly increased from 0.21μg/mL to 250μg/mL. The imaging capability of SF/Gd-liposomes were tested by in-vitro and the in-vivo imaging ability tests and the results confirmed that SF/Gd-liposomes could be served as an effective contrast agent. The design of SF/Gd-liposomes allowed the MRI-guided in vivo visualization of the delivery and biodistribution of liposome. In the in vivo antitumor studies, SF/Gd-liposomes had better antitumor effects in H22 tumor-bearing mice than SF solution (oral or i.v. administration) (P<0.05). These findings indicated that the SF/Gd-liposomes could be used as the promising nano-carriers for the MRI-guided in vivo visualization of the delivery and HCC treatment. PMID:26844644

  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. Inhalation Delivery of a Novel Diindolylmethane Derivative for the Treatment of Lung Cancer

    PubMed Central

    Ichite, Nkechi; Chougule, Mahavir; Patel, Apurva R.; Jackson, Tanise; Safe, Stephen; Singh, Mandip

    2010-01-01

    The purpose of this study was to determine the anticancer efficacy of 1,1-bis (3? indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC6H5) by inhalation delivery alone and in combination with i.v. docetaxel (Doc) in a murine model for lung cancer. An aqueous DIM-C-pPhC6H5 formulation was characterized for its aerodynamic properties. Tumor-bearing athymic nude mice were exposed to nebulized DIM-C-pPhC6H5, Doc, or combination (DIM-C-pPhC6H5 plus Doc) using a nose-only exposure technique. The aerodynamic properties included mass median aerodynamic diameter of 1.8 0.3 ?m and geometric standard deviation of 2.31 0.02. Lung weight reduction in mice treated with the drug combination was 64 % compared to 40 % and 47 % in mice treated with DIM-C-pPhC6H5 aerosol and Doc alone respectively. Combination treatment decreased expression of akt, cyclinD1, survivin, Mcl-1, NF-kB, IKB?, P-IkB?, VEGF, and increased expression of JNK2 and Bad compared to tumors collected from single-agent treatment and control groups. DNA fragmentation was also enhanced in mice treated with the drug combination mice compared to Doc or DIM-C-pPhC6H5 alone. Combination treatment decreased expressions of VEGF & CD31 compared to single agent treated and control groups. These results suggest that DIM-C-pPhC6H5 aerosol enhanced the anticancer activity of Doc in a lung cancer model by activating multiple signaling pathways. The study provides evidence that DIM-C-pPhC6H5 can be used alone or in combination with other drugs for the treatment of lung cancer using the inhalation delivery approach. PMID:20978159

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

    PubMed Central

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

    2015-01-01

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

  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. 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

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

    PubMed Central

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

    2013-01-01

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

  2. 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.

  3. 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

  4. 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

  5. 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

  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. 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

  8. 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

  9. Development and optimization of hydroxyapatite-ofloxacin implants for possible bone delivery in osteomyelitis treatment.

    PubMed

    Nayak, Amit Kumar; Hasnain, M Saquib; Malakar, Jadupati

    2013-04-01

    The present study deals with preparation, optimization and in-vitro drug release study of hydroxyapatite (HAp)- ofloxacin for bone-implantable delivery in osteomyelitis treatment. The effect of drug amount added, and orthophosphoric acid addition rate as process parameters on the drug loading into HAp-system by precipitation method was optimized by using 32 factorial design. The response surface methodology utilizing polynomial equation was used to search for optimal drug loading into HAp-system. The responses observed coincided well with the predicted values obtained through optimization technique. HAp-ofloxacin bone-implants were manufactured using synthesized HAp-ofloxacin composite powders and 2 % w/v aqueous solution of sodium alginate was used as binder. Characterization of the delivery system was done by FTIR spectroscopy. The in-vitro ofloxacin release from optimized HAp-ofloxacin bone-implants was slow and sustained over 10 weeks. The drug release pattern was correlated well with Korsmeyer-Peppas model and was followed by Fickian (diffusional) release mechanism. PMID:23092295

  10. Review article: evolutionary advances in the delivery of aminosalicylates for the treatment of ulcerative colitis.

    PubMed

    Cohen, R D

    2006-08-01

    Ulcerative colitis is a chronic and debilitating disease that involves inflammation of the colonic mucosa. Current therapies aim to reduce the symptom burden of ulcerative colitis and maintain disease quiescence. The standard first-line treatment for mild-to-moderate ulcerative colitis is 5-aminosalicylate therapy, which is available in oral and rectal (topical) formulations. While current 5-aminosalicylate formulations are effective in the majority of patients, they are associated with a number of limitations including inconvenient dosing regimens and poor patient acceptability, which may lead to non-compliance with prescribed therapy. A variety of improved delivery mechanisms have been developed in an effort to overcome these limitations. Micropellet formulations and high-dose tablets appear to offer comparable efficacy and tolerability to conventional formulations, although any benefit in terms of long-term patient compliance remains to be proven. Novel methods of delivery, such as those using a combination of hydrophilic and lipophilic matrices, designed to provide once-daily dosing in a high-strength tablet, may offer a significant improvement in the therapy of active and quiescent ulcerative colitis. This review examines the limitations of current 5-aminosalicylate formulations and reports on the evolution of novel oral formulations designed to overcome these limitations, maximize patient compliance during both induction and maintenance of quiescence, and optimize overall clinical outcomes. PMID:16886912

  11. 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.

  12. New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment.

    PubMed

    Chávez-Fumagalli, Miguel Angel; Ribeiro, Tatiana Gomes; Castilho, Rachel Oliveira; Fernandes, Simone Odília Antunes; Cardoso, Valbert Nascimento; Coelho, Cecília Steinberg Perilo; Mendonça, Débora Vasconcelos Costa; Soto, Manuel; Tavares, Carlos Alberto Pereira; Faraco, André Augusto Gomes; Coelho, Eduardo Antonio Ferraz

    2015-01-01

    Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio. PMID:26107999

  13. Pulmonary delivery of cisplatin-hyaluronan conjugates via endotracheal instillation for the treatment of lung cancer

    PubMed Central

    Xie, Yumei; Aillon, Kristin L.; Cai, Shuang; Christian, Jason M.; Davies, Neal M.; Berkland, Cory J.; Forrest, M. Laird

    2010-01-01

    Cisplatin (CDDP) intravenous treatments suffer several dose-limiting toxicity issues. Hyaluronan (HA), a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system. An alteration in input rate and administration route through pulmonary delivery of hyaluronan-cisplatin conjugate (HA-Pt) may increase local lung CDDP concentrations and decrease systemic toxicity. Sprague-Dawley rats were split into four groups: i.v. CDDP (3.5 mg/kg), i.v. HA-Pt conjugate (3.5 mg/kg equivalent CDDP), lung instillation CDDP and lung instillation HA-Pt conjugate. Total platinum level in the lungs of the HA-Pt lung instillation group was 5.7-fold and 1.2-fold higher than the CDDP intravenous group at 24 h and 96 h, respectively. A 1.1-fold increase of Pt accumulation in lung draining nodes for the HA-Pt lung instillation group was achieved at 24 h relative to the CDDP i.v. group. In the brain and kidneys, the CDDP i.v. group had higher tissue/plasma ratios compared to the HA-Pt lung instillation group. Augmented tissue distribution from CDDP i.v. could translate into enhanced tissue toxicity compared to the altered input rate and distribution of the intrapulmonary nanoformulation. In conclusion, a local pulmonary CDDP delivery system was developed with increased platinum concentration in the lungs and draining nodes compared to i.v. therapy. PMID:20363303

  14. Ask Advise Connect: A New Approach to Smoking Treatment Delivery in Healthcare Settings

    PubMed Central

    Vidrine, Jennifer Irvin; Shete, Sanjay; Cao, Yumei; Greisinger, Anthony; Harmonson, Penny; Sharp, Barry; Miles, Lyndsay; Zbikowski, Susan M.; Wetter, David W.

    2013-01-01

    Background Several national healthcare-based smoking cessation initiatives have been recommended to facilitate the delivery of evidence-based treatments such as those delivered by quitlines. The most notable examples are the 5 A’s (i.e., Ask, Advise, Assess, Assist, Arrange) and Ask Advise Refer (AAR). Unfortunately, primary care referrals to quitlines are low and the majority of smokers referred fail to call for assistance. This study evaluated a new approach -Ask Advise Connect (AAC) - designed to address barriers to linking smokers with treatment. Methods A pair-matched-two-treatment arm group-randomized design in 10 family practice clinics in the Houston, TX metropolitan area was utilized. Five clinics were randomized to AAC (intervention) and five were randomized to AAR (control). In both conditions, clinic staff were trained to assess and record the smoking status of all patients at all visits in the electronic health record (EHR), and smokers were given brief advice to quit. In AAC, the names and phone numbers of smokers who agreed to be connected were sent electronically to the Quitline daily, and patients were proactively called by the Quitline within 48 hours. In AAR, smokers were offered a Quitline referral card and encouraged to call on their own. All data were collected between February and December 2011. The primary outcome – impact – was based on the RE-AIM conceptual framework. Impact was defined as the proportion of all identified smokers that enrolled in treatment. Results In AAC, 7.8% of all identified smokers enrolled in treatment versus 0.6% in AAR (t(4)=9.19, p=0.0008, OR=11.60 (95% CI 5.53-24.32), a 13-fold increase in the proportion of smokers enrolling in treatment in AAC compared to AAR. Conclusions The system changes implemented in AAC could be adopted broadly by other healthcare systems and AAC has tremendous potential to reduce tobacco-related morbidity and mortality. PMID:23440173

  15. 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

  16. 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 confirm that Co-60 tomotherapy is capable of providing state-of-the-art conformal dose delivery and could be used for the treatment of targets in both small and larger separation anatomical regions.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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 are deliverable. Comparing the Co-60 dose distributions and DVHs to the IMRT plans from the clinic indicates that Co-60 is able to provide similar dose conformality to targets and dose sparing to critical organs. The results of the novel MLC segmentation algorithm and the photon fluence model proposed in this work compared well with the Monte Carlo calculations. In summary, the investigations presented in this thesis confirm that Co-60 tomotherapy is indeed capable of providing state-of-the-art conformal dose delivery. We have shown that the perceived beam limitations often identified with Co-60 (e.g., lower penetration, source size artifacts under small field collimation, and larger penumbra) are negligible when using intensity modulated techniques.

  2. 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 48h, 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 these layers of the skin do not retain the nanoparticles. Based on our data, we found that the novel Au-3MPS@MTX conjugate is an effective non-toxic carrier for the satisfactory percutaneous absorption of Methotrexate and could help in possible topical treatment of psoriasis. PMID:26852097

  3. Treatment of parturition-induced rupture of pubic symphysis after spontaneous vaginal delivery.

    PubMed

    Gräf, C; Sellei, R M; Schrading, S; Bauerschlag, D O

    2014-01-01

    Parturition-induced rupture of pubic symphysis is an uncommon but severe complication of delivery. Characteristic symptoms are an immediate onset of suprapubic and/or sacroiliac pain within the first 24 hours postpartum, often accompanied by an audible crack. Diagnosis can be confirmed by imaging including X-ray, Magnet Resonance Imaging (MRI), and ultrasound. However, there is no consensus on the optimal therapy. Conservative treatment is predominantly used. It has been reported that, in cases of extreme symphyseal rupture with pelvic instability or persisting pain after conservative therapy, operative treatment achieves a successful outcome. In this report, we present a case of a twenty-year-old primigravida who developed suprapubic pain after a nonoperative vaginal birth with shoulder dystocia. A rupture of pubic symphysis with a gap of 60 mm was confirmed by means of X-ray and MRI. Simultaneously, other pelvic joint injuries could be excluded. Operative treatment by an open reduction and internal plate fixation yielded excellent results. PMID:24551465

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

    NASA Astrophysics Data System (ADS)

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

    2002-11-01

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

  5. 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

  6. Intra-articular delivery of chondroitin sulfate for the treatment of joint defects in rabbit model.

    PubMed

    Hui, James H; Chan, Shzu-Wei; Li, Jun; Goh, James C H; Li, Li; Ren, X F; Lee, Eng Hin

    2007-10-01

    Chondroitin sulfate (CS) is considered as a possible candidate for the treatment of joint defect. This study is to evaluate the efficacy of intra-articular injection of CS carried by hydrogel in the treatment of chondral defects in adult rabbit models. Inclusion of CS (0-50 microg/ml) in in vitro chondrocyte culture exerts a dose-dependent increase in cell proliferation. To select for optimal carrier for in vivo study, the release kinetic of CS embedded in five types of hydrogel was studied using fluorescence technique and their biocompatibilities in vivo were investigated by injecting the CS-hydrogel into rabbit knees. alpha-CD-EG 4400 hydrogel was chosen as the carrier based on progressively released CS from the hydrogel, with 80% released by in one week while the remaining 20% was retained for 30 days. In vivo studies showed high biocompatibility of CS-hydrogel. To evaluate the efficacy of CS in the treatment of cartilage injury, chondral defects were created in femoral medial condyle (punch diameter 2.7 mm) or trochlea (punch diameter 3.5 mm) of the rabbits without damaging subchondral bone. CS (100 mg/ml) in 0.5 ml alpha-CD-EG 4400 hydrogel was then injected into the knee joint. Hydrogel and saline served as controls. On day 50 the chondral defect in the saline group showed no signs of healing and defect treated with hydrogel alone was covered with a thin and slightly irregular layer of fibrous tissue. The CS-hydrogel group showed a thicker layer composed of both hyaline and fibrocartilage. The modulus of elasticity was the highest in the CS-hydrogel group and lowest in the group injected with saline only. Our results suggest that intra-articular delivery of CS by alpha-CD-EG 4400 improved the biomechanical and histological properties of the repaired cartilage. It may be an effective treatment for cartilage injury. PMID:17653606

  7. CONVECTION ENHANCED DELIVERY OF CARBOPLATIN IN COMBINATION WITH RADIOTHERAPY FOR THE TREATMENT OF BRAIN TUMORS

    PubMed Central

    Yang, Weilian; Huo, Tianyao; Barth, Rolf F.; Gupta, Nilendu; Weldon, Michael; Grecula, John C.; Ross, Brian D.; Hoff, Benjamin A.; Chou, Ting-Chao; Rousseau, Julia; Elleaume, Hlne

    2015-01-01

    The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of carboplatin in combination with radiotherapy for treatment of the F98 rat glioma. Tumor cells were implanted stereotactically into the brains of syngeneic Fischer rats, and 13 or 17 d. later carboplatin (20 ?g/10 ?L) was administered by either CED over 30 min or by Alzet osmotic pumps (0.5 ?g/?L/h for 168 h.) beginning at 7 d after tumor implantation. Rats were irradiated with a 15 Gy fractionated dose (5 Gy 3) of 6 MV photons to the whole brain beginning on the day after drug administration. Other groups of rats received either carboplatin or X-irradiation alone. The tumor carboplatin concentration following CED of 20 ?g in 10 ?L was 10.4 ?g/g, which was equal to that observed following i.v. administration of 100 mg/kg b.w. Rats bearing small tumors, treated with carboplatin and X-irradiation, had a mean survival time (MST) of 83.4 d following CED and 111.8 d following pump delivery with 40% of the latter surviving >180 d (i.e. cured) compared to 55.2 d for CED and 77.2 d. for pump delivery of carboplatin alone and 31.8 d and 24.2 d, respectively, for X-irradiated and untreated controls. There was no microscopic evidence of residual tumor in the brains of all long-term survivors. Not surprisingly, rats with large tumors had much shorter MSTs. Only modest increases in MSTs were observed in animals that received either oral administration or CED of temozolomide plus X-irradiation (23.2 d and 29.3 d) compared to X-irradiation alone. The present survival data, and those previously reported by us, are among the best ever obtained with the F98 glioma model. Initially, they could provide a platform for a Phase I clinical trial to evaluate the safety and potential therapeutic efficacy of CED of carboplatin in patients with recurrent glioblastomas, and ultimately a Phase II trial of carboplatin in combination with radiation therapy. PMID:20577779

  8. Novel Thermosensitive Pentablock Copolymers for Sustained Delivery of Proteins in the Treatment of Posterior Segment Diseases

    PubMed Central

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

    2015-01-01

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

  9. Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment.

    PubMed

    Voss, Karsten; Falke, Karen; Bernsdorf, Arne; Grabow, Niels; Kastner, Christian; Sternberg, Katrin; Minrath, Ingo; Eickner, Thomas; Wree, Andreas; Schmitz, Klaus-Peter; Guthoff, Rudolf; Witt, Martin; Hovakimyan, Marina

    2015-09-28

    In this study we present the development of an injectable polymeric drug delivery system for subconjunctival treatment of primary open angle glaucoma. The system consists of hyaluronic acid sodium salt (HA), which is commonly used in ophthalmology in anterior segment surgery, and an isocyanate-functionalized 1,2-ethylene glycol bis(dilactic acid) (ELA-NCO). The polymer mixtures with different ratios of HA to ELA-NCO (1/1, 1/4, and 1/10 (v/v)) were investigated for biocompatibility, degradation behavior and applicability as a sustained release system. For the latter, the lipophilic latanoprost ester pro-drug (LA) was incorporated into the HA/ELA-NCO system. In vitro, a sustained LA release over a period of about 60days was achieved. In cell culture experiments, the HA/ELA-NCO (1/1, (v/v)) system was proven to be biocompatible for human and rabbit Tenon's fibroblasts. Examination of in vitro degradation behavior revealed a total mass loss of more than 60% during the observation period of 26weeks. In vivo, LA was continuously released for 152days into rabbit aqueous humor and serum. Histological investigations revealed a marked leuko-lymphocytic infiltration soon after subconjunctival injection. Thereafter, the initial tissue reaction declined concomitantly with a continuous degradation of the polymer, which was completed after 10months. Our study demonstrates the suitability of the polymer resulting from the reaction of HA with ELA-NCO as an injectable local drug delivery system for glaucoma therapy, combining biocompatibility and biodegradability with prolonged drug release. PMID:26160303

  10. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

    PubMed

    Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

    2015-12-10

    The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel delivery systems will help iterate towards prevention, functional cure and eventually the eradication of HIV infection. PMID:26315816

  11. 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

  12. Implantable technology for long-term delivery of nalmefene for treatment of alcoholism.

    PubMed

    Costantini, Lauren C; Kleppner, Sofie R; McDonough, Joseph; Azar, Marc R; Patel, Raj

    2004-09-28

    Pharmacotherapy treatment for alcoholism is limited by poor compliance, adverse effects, and fluctuating drug levels after bolus administration. A long-term delivery system would improve upon these limitations. The current study describes the characterization of a sustained release implant containing nalmefene, an opioid antagonist, for treatment of alcoholism. Nalmefene was blended with ethylene vinyl acetate (EVA), extruded into 2.8 mm x 27 mm rods, and coated with EVA to optimize release. In vitro release was determined by HPLC, and in vivo release characteristics after subcutaneous implantation into rats were determined by LC-MS/MS analyses. Extrusion produced rods containing 80.09 +/- 6.0 mg nalmefene. In vitro release was high from the uncoated rods, and they were depleted of drug fairly quickly; however EVA coatings maintained release over longer periods. The 25 wt.% coated rods provided in vitro release of 0.36 mg/day/rod, and in vivo release of 0.29 mg/day/rod over 6 months, and showed dose-dependent nalmefene plasma concentrations (one rod: 3.33 +/- 0.56 ng/ml, three rods: 10.19 +/- 2.31 ng/ml). After explantation, nalmefene plasma concentrations were undetectable by 6 h. A sustained release nalmefene rod provides 6 months of drug with no adverse effects. PMID:15363499

  13. 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

  14. 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

  15. Role of gold nanoparticles as drug delivery vehicles for chondroitin sulfate in the treatment of osteoarthritis.

    PubMed

    Dwivedi, Priyanka; Nayak, Vijayashree; Kowshik, Meenal

    2015-01-01

    Osteoarthritis is a disease which is characterized by joint pain, swelling and stiffness. Articular cartilage has limited self-repair capacity due to its avascular and aneural nature. In this work, we show the use of gold nanoparticles (AuNps) for enhancing the delivery of chondroitin sulfate (CS), a drug used in the treatment of osteoarthritis (OA). AuNps were synthesized and were characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-Ray diffraction analysis. AuNps were combined with CS (AuNps-CS) and their effect on primary goat chondrocytes was studied using MTT assay, Hoechst staining, production of glycosaminoglycan and collagen. Cell viability studies by MTT revealed that AuNps-CS stimulate cell proliferation. A two-fold increase in GAG and collagen production was observed in presence of AuNps-CS combination as compared to native CS, indicating that this combination stimulates chondrocyte proliferation and enhances extracellular matrix production (ECM). Hence, this study exhibits the potential of AuNps as a carrier of CS for treatment of osteoarthritis. PMID:26193993

  16. 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

  17. 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

  18. 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…

  19. 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 PTV, for both VMAT and RapidArc techniques. Conclusion The study concludes that a variable gantry speed with variable dose rate is important for efficient arc therapy delivery. RapidArc presents a slight improvement in the OAR sparing with better target coverage when compared to Elekta VMAT. Trivial differences were noted in all the plans for organ at risk but the two techniques provided satisfactory conformal avoidance and conformation. PMID:24416535

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

    PubMed

    Henshaw, Joshua; Mossop, Brian; Yuan, Fan

    2008-08-01

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

  1. 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. Iranian physicians were fully aware of systemic effects of topical medications, including prescription drugs through the nose. The study of ancient medical texts helps us in identification of herbal medicine and the investigation of new way for the preparation of drugs. PMID:25068043

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

    PubMed

    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

  3. 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.

  4. Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis.

    PubMed

    Pathak, Meenakshi; Turner, Mark; Palmer, Cheryn; Coombes, Allan G A

    2014-09-01

    Microporous, poly (ɛ-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis. PMID:24682036

  5. 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.

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

    PubMed Central

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

    2009-01-01

    Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder. PMID:19242523

  7. 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

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

    PubMed

    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

    2015-10-01

    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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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:26929622

  15. 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 resonance, was measured during laser application. Successful release of doxorubicin via laser application was measured with fluorescence measurements providing proof that the doxorubicin was successfully intercalated and released.

  16. 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:26929622

  17. Home hospice acupuncture: a preliminary report of treatment delivery and outcomes.

    PubMed

    Kaufman, Karen; Salkeld, Ellen J

    2008-01-01

    In recent years, complementary and alternative medicine modalities, including acupuncture, have been incorporated intohospice careboth to address symptom distress and to enhance quality of life. Beginning in 1997, Kaiser Permanente Northwest Hospice began offering limited acupuncture services to hospice patients and, in some cases, their caregivers. Data collection-comprising a chart review (n = 71) and in-depth interviews with the two program acupuncturists-was initiated to explore in a preliminary fashion both the processes involved in acupuncture delivery and outcomes associated with this intervention. Information culled from the patient charts (representing the year 2003) revealed a median age of 68.5 years, a cancer diagnosis in 63% of cases, and a median hospice length of stay of 102 days. The most commonly cited chief complaints presented to the acupuncturists included pain (70%), anxiety (45%), shortness of breath (27%), and nausea/vomiting (14%). Patients received a median of three acupuncture treatments; excellent or good results were noted in the charts of 34% of patients whose chief complaint was pain, in 31% of anxiety chief complaints, in 22% of shortness-of-breath chief complaints, and in 29% for nausea/vomiting chief complaints. The program acupuncturists described their practice with this group of patients as a departure from how they treat patients in a typical practice context. They described a greater focus on providing comfort through ameliorating symptoms and a diminished focus on more holistic goals, which often are typical elements in an acupuncture intervention. Nonetheless, acupuncturists also observed instances of outcomes in psychologic, social, and spiritual domains, regardless of whether these outcomes were the principal focus of treatment. These data add to the accumulating anecdotal reports suggesting that acupuncture is a promising adjunctive therapy for those nearing the end of life in the home hospice setting. More in-depth and precise assessment is warranted to comprehensively evaluate acupuncture as a viable adjunct to current usual and customary hospice care. PMID:21369508

  18. 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

  19. 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.

  20. Treatment Planning and Delivery of Whole Brain Irradiation with Hippocampal Avoidance in Rats

    PubMed Central

    Cramer, C. K.; Yoon, S. W.; Reinsvold, M.; Joo, K. M.; Norris, H.; Hood, R. C.; Adamson, J. D.; Klein, R. C.; Kirsch, D. G.; Oldham, M.

    2015-01-01

    Background Despite the clinical benefit of whole brain radiotherapy (WBRT), patients and physicians are concerned by the long-term impact on cognitive functioning. Many studies investigating the molecular and cellular impact of WBRT have used rodent models. However, there has not been a rodent protocol comparable to the recently reported Radiation Therapy Oncology Group (RTOG) protocol for WBRT with hippocampal avoidance (HA) which is intended to spare cognitive function. The aim of this study was to develop a hippocampal-sparing WBRT protocol in Wistar rats. Methods The technical and clinical challenges encountered in hippocampal sparing during rat WBRT are substantial. Three key challenges were identified: hippocampal localization, treatment planning, and treatment localization. Hippocampal localization was achieved with sophisticated imaging techniques requiring deformable registration of a rat MRI atlas with a high resolution MRI followed by fusion via rigid registration to a CBCT. Treatment planning employed a Monte Carlo dose calculation in SmART-Plan and creation of 0.5cm thick lead blocks custom-shaped to match DRR projections. Treatment localization necessitated the on-board image-guidance capability of the XRAD C225Cx micro-CT/micro-irradiator (Precision X-Ray). Treatment was accomplished with opposed lateral fields with 225 KVp X-rays at a current of 13mA filtered through 0.3mm of copper using a 40x40mm square collimator and the lead blocks. A single fraction of 4Gy was delivered (2Gy per lateral field) with a 41 second beam on time per field at a dose rate of 304.5 cGy/min. Dosimetric verification of hippocampal sparing was performed using radiochromic film. In vivo verification of HA was performed after delivery of a single 4Gy fraction either with or without HA using γ-H2Ax staining of tissue sections from the brain to quantify the amount of DNA damage in rats treated with HA, WBRT, or sham-irradiated (negative controls). Results The mean dose delivered to radiochromic film beneath the hippocampal block was 0.52Gy compared to 3.93Gy without the block, indicating an 87% reduction in the dose delivered to the hippocampus. This difference was consistent with doses predicted by Monte Carlo dose calculation. The Dose Volume Histogram (DVH) generated via Monte Carlo simulation showed an underdose of the target volume (brain minus hippocampus) with 50% of the target volume receiving 100% of the prescription isodose as a result of the lateral blocking techniques sparing some midline thalamic and subcortical tissue. Staining of brain sections with anti-phospho-Histone H2A.X (reflecting double-strand DNA breaks) demonstrated that this treatment protocol limited radiation dose to the hippocampus in vivo. The mean signal intensity from γ-H2Ax staining in the cortex was not significantly different from the signal intensity in the cortex of rats treated with WBRT (5.40 v. 5.75, P = 0.32). In contrast, the signal intensity in the hippocampus of rats treated with HA was significantly lower than rats treated with WBRT (4.55 v. 6.93, P = 0.012). Conclusion Despite the challenges of planning conformal treatments for small volumes in rodents, our dosimetric and in vivo data show that WBRT with HA is feasible in rats. This study provides a useful platform for further application and refinement of the technique. PMID:26636762

  1. 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

  2. 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

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

    NASA Astrophysics Data System (ADS)

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

    2010-01-01

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

  4. Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas

    PubMed Central

    Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

    2015-01-01

    Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy. PMID:25853310

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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-Franois; Balosso, Jacques; Estve, Franois; Elleaume, Hlne

    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 (6?g/20?L) was administered i.c. by CED at a flow rate of 0.5?L/min. On the following day the animals were irradiated with a single 15 Gy dose of X-rays, administered by a linear accelerator (LINAC) or 78.8 keV synchrotron X-rays at the European Synchrotron Radiation Facility (ESRF). Untreated controls had a mean survival time (MST) standard error of 24 1 d. compared to > 59 13 d. for rats that received cisplatin alone with 13% of the latter surviving >200 d. Rats that received cisplatin in combination with either 6 MV (LINAC) or 78.8 keV (synchrotron) X-rays had almost identical MSTs of > 7518 d. and > 7419 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

  10. 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 20 times lower than that of a patient undergoing standard 18F-FDG treatment. When using a combination of short lived nuclides such as 15O (half-life: 2 min) and 11C (half-life: 20 min) with low activity it is not optimal to use clinical reconstruction protocols. Thus, it might be desirable to further optimize reconstruction parameters as well as to address hardware improvements in realizing in vivo treatment verification with PET/CT in the future. A significant improvement with regard to 15O imaging could also be expected by having the PET/CT unit located close to the radiation treatment room.

  11. The effect of prenatal treatment with steroids and preterm delivery in a model of myelomeningocele on the rabbit foetus.

    PubMed

    Fontecha, César G; Peiró, Jose L; Aguirre, Marius; Soldado, Francesc; Paz, Patricia; Oria, Marc; Torán, Núria; Martinez-Ibáñez, Vicenç

    2007-05-01

    Damage of neural elements (spinal cord and encephalus) in myelomeningocele (MMC) seems to be progressive during gestation because of amniotic fluid chemical contact and continuous leakage of CSF. We studied the effect of preterm delivery and steroid treatment in a model of MMC in the rabbit foetus. Twelve New Zealand White rabbits underwent laparotomy and hysterotomy at 23 days of gestation. Fifty-nine out of 107 foetuses underwent lumbar laminectomy (three to four levels). Dura was opened to expose the neural elements to the amniotic fluid. Six rabbits underwent caesarean section on gestational day 31 for fetal harvest; three of them had no treatment (group T) and three received corticosteroid treatment (group TC). The other six rabbits underwent caesarean section on gestational day 29 for fetal harvest (preterm delivery); three of them had no treatment (group P) and three received corticosteroid treatment (group PC). Alive newborns were clinically, neurophysiologically and histologically analysed. None of mothers died during the procedure. After birth, animals in group preterm showed statistically significant less deformity than animals in group at term. Lower kyphosis was observed in group PC (preterm and steroids). Pain related and spontaneous mobility of lower extremities was higher in groups treated with corticosteroids (TC and PC). Only newborns at term (T and TC groups) showed response to evoked potentials (CMEPs). The response was earlier and higher in group treated with steroids (TC). Histologically, we observed progressive lesion of the spinal cord. Groups treated with steroids (TC and PC) show less inflammatory response. Arnold-Chiari malformation was present in all groups. Animals in group preterm with steroids show statistically significant less herniation than those group at term. Preterm delivery and prenatal steroid therapy seem to be an effective treatment to get less neural injury (spinal cord and encephalus) in myelomeningocele foetuses. PMID:17372742

  12. 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

  13. 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

  14. [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

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

    PubMed

    Garg, Tarun

    2016-02-01

    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

  16. Accurate treatments of electronic correlation: Phase transitions in an idealized one-dimensional ferroelectric and modelling experimental quantum dots

    NASA Astrophysics Data System (ADS)

    Wilkens, Timothy James

    2001-12-01

    Quantum Monte Carlo (QMC) is one of the most powerful methods for solving many-body problems in Physics and Chemistry. MC sampling allows one to measure physical properties systems with very complicated wave functions that incorporate correlation between the electrons. Additionally, QMC has O(N3) scaling verses exponential scaling for methods such as Configuration Interaction and "exact diagonalization", and its perfect parallelism allows one to speed up computation with little effort on large parallel computers. Our work has focussed on two systems. The first is a 1D ionic Hubbard model with a complex phase diagram that we find to exhibit a ferroeletric "bond ordered" phase. A new many-body berry's phase formulation of the electronic polarization and localization is used in conjunction with QMC to analyze whether a bond order phase exists between the customary band and Mott insulating phases. The bond order and bond order correlation functions are measured to illustrate the stability of this intermediate state, and phase swapping between two degenerate states of bond order (+/-B) is observed. We propose that the Mott state it is unstable to bond ordering for any degree of ionicity. The second system we have studied is a set of idealized (harmonic) and realistic quantum dots. Two idealized dots, spherical and squashed, quasi-2D structures, are analyzed. In the first QMC is contrasted with a large set of commonly used electronic structure methods including MSFT, KLI, LSDA, and CCSD, and in the second we scrutinize whether SDW states truly exist as predicted by LSDA. In conjunction with the Computational Electronics Group at the Beckman Institute, we have performed QMC calculations on realistically modelled quantum dots in the effective mass approximation. The potentials of these dots are determined using the FEM method to solve Poisson's equation and the effective mass is allowed to spatially vary in our QMC simulations. We find that in arrays of QD's, LSDA may be insufficiently accurate to determine the proper spin states of the electrons. Additionally, we illustrate that QMC has a bright future ahead of it in modelling such devices using arbitrary functions represented on grids using splines.

  17. siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery.

    PubMed

    Gomes, Maria João; Martins, Susana; Sarmento, Bruno

    2015-05-01

    As the population ages, brain pathologies such as neurodegenerative diseases and brain cancer increase their incidence, being the need to find successful treatments of upmost importance. Drug delivery to the central nervous system (CNS) is required in order to reach diseases causes and treat them. However, biological barriers, mainly blood-brain barrier (BBB), are the key obstacles that prevent the effectiveness of possible treatments due to their ability to strongly limit the perfusion of compounds into the brain. Over the past decades, new approaches towards overcoming BBB and its efflux transporters had been proposed. One of these approaches here reviewed is through small interfering RNA (siRNA), which is capable to specifically target one gene and silence it in a post-transcriptional way. There are different possible functional proteins at the BBB, as the ones responsible for transport or just for its tightness, which could be a siRNA target. As important as the effective silence is the way to delivery siRNA to its anatomical site of action. This is where nanotechnology-based systems may help, by protecting siRNA circulation and providing cell/tissue-targeting and intracellular siRNA delivery. After an initial overview on incidence of brain diseases and basic features of the CNS, BBB and its efflux pumps, this review focuses on recent strategies to reach brain based on siRNA, and how to specifically target these approaches in order to treat brain diseases. PMID:25796492

  18. 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

  19. 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

  20. 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

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

    PubMed

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

    2014-11-01

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

  2. 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.

  3. 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

    2016-03-16

    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

  4. 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…

  5. Rupture of an aneurysm of the ovarian artery following delivery and endovascular treatment.

    PubMed

    Poilblanc, Mathieu; Winer, Norbert; Bouvier, Antoine; Gillard, Philippe; Boussion, Franoise; Aub, Christophe; Descamps, Philippe

    2008-10-01

    We report a case of spontaneous rupture of an ovarian artery aneurysm, 5 days after delivery. Severe abdominal pain justified a computed tomography scan, which revealed a massive retroperitoneal hematoma. Arteriography showed the rupture of an ovarian artery aneurysm that was successfully embolized using microcoils. PMID:18599014

  6. 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

  7. Closed-loop insulin delivery for treatment of type 1 diabetes

    PubMed Central

    2011-01-01

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

  8. 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. Cancer Res; 76(6); 1320-34. ©2015 AACR. PMID:26719526

  9. 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.

  10. 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.

  11. 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 beams.

  12. 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.

  13. 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

  14. 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

  15. Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast cancer in vitro and in vivo.

    PubMed

    Fan, Wei; Wang, Xiang; Ding, Baoyue; Cai, Haimin; Wang, Xudong; Fan, Yueqi; Li, Yong; Liu, Shenghui; Nie, Suifeng; Lu, Qiping

    2016-04-01

    The high transfection efficiency and enhanced therapeutic effect of drug delivery systems developed in recent years imply that ligand-decorated nanocarriers are potentially targeted vectors for breast cancer treatment. Thioaptamer (TA)-modified nanoparticles (NPs) designed in this study mainly consisted of ligand TA and dendritic polyamidoamine (PAMAM). Knowing that TA can bind to CD44-receptors in breast cancer, this study was intended to validate the safety and feasibility of systemic miRNA delivery to breast cancer cells by TA-PEG-PAMAM/miRNA (polyethylene glycol - PEG), testify its tumor targeting efficiency in vitro, and observe its biodistribution when it was administered systemically to a xenograft mouse model of breast cancer. The in vivo and ex vivo imaging results in human breast cancer tumor-bearing mice showed that TA-modification was able to enhance the accumulation of NPs in the breast cancer tumor. Our data showed that TA-NPs did not induce functional impairment to normal tissues and vital organs. TA-NPs may prove to be a safe and effective miRNA deliver system for breast cancer treatment, and could be widely used in pre-clinical and eventually clinical arenas of breast cancer treatment. PMID:26299192

  16. 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

  17. 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 fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered. PMID:20199661

  18. 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

  19. 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

  20. 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

  1. Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging.

    PubMed

    Han, Liang; Kong, Derek K; Zheng, Ming-Qiang; Murikinati, Sasidhar; Ma, Chao; Yuan, Peng; Li, Liyuan; Tian, Daofeng; Cai, Qiang; Ye, Chunlin; Holden, Daniel; Park, June-Hee; Gao, Xiaobin; Thomas, Jean-Leon; Grutzendler, Jaime; Carson, Richard E; Huang, Yiyun; Piepmeier, Joseph M; Zhou, Jiangbing

    2016-04-26

    The blood-brain barrier (BBB) is partially disrupted in brain tumors. Despite the gaps in the BBB, there is an inadequate amount of pharmacological agents delivered into the brain. Thus, the low delivery efficiency renders many of these agents ineffective in treating brain cancer. In this report, we proposed an "autocatalytic" approach for increasing the transport of nanoparticles into the brain. In this strategy, a small number of nanoparticles enter into the brain via transcytosis or through the BBB gaps. After penetrating the BBB, the nanoparticles release BBB modulators, which enables more nanoparticles to be transported, creating a positive feedback loop for increased delivery. Specifically, we demonstrated that these autocatalytic brain tumor-targeting poly(amine-co-ester) terpolymer nanoparticles (ABTT NPs) can readily cross the BBB and preferentially accumulate in brain tumors at a concentration of 4.3- and 94.0-fold greater than that in the liver and in brain regions without tumors, respectively. We further demonstrated that ABTT NPs were capable of mediating brain cancer gene therapy and chemotherapy. Our results suggest ABTT NPs can prime the brain to increase the systemic delivery of therapeutics for treating brain malignancies. PMID:26967254

  2. 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 subgroup analyses, such as targeted versus non-targeted DDS or IV versus IP administration route, did not identify specific characteristics of DDS that affected treatment efficacy. This systematic review shows the potential, but also the limitations of chemotherapy by drug delivery systems for ovarian cancer treatment. For future animal research, we emphasize that data need to be reported with ample attention to detailed reporting. PMID:26713240

  3. 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 right-left (RL), anterior-posterior (AP), and superior-inferior (SI) axes, respectively. Simulations showed that while oscillating (stationary) motion cannot be effectively represented in 3D, linearly drifting (nonstationary) motion is detectable with good accuracy. These results show that measuring prostate intrafraction motion using a single kV imager during radiotherapy is feasible and can be performed with acceptable accuracy.

  4. 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 advancements and contribute to the translation of nanotechnology across medical disciplines. PMID:20149882

  5. 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

  6. 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

  7. 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

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

    PubMed Central

    Shi, Changying; Guo, Dandan; Wang, Xu; Luo, Juntao

    2014-01-01

    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

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

    PubMed

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

    2012-07-01

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

  10. 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

  11. Sustained prolonged topical delivery of bioactive human insulin for potential treatment of cutaneous wounds.

    PubMed

    Hrynyk, Michael; Martins-Green, Manuela; Barron, Annelise E; Neufeld, Ronald J

    2010-10-15

    Skin damaged by heat, radiation, or chemical exposure is difficult to treat and slow to heal. Indeed full restoration of the tissue is difficult to obtain. Sub-dermal insulin injection was recently shown to stimulate wound healing of the skin by accelerating wound closure, stimulating angiogenesis and inducing a regenerative process of healing. We have developed a topical delivery vehicle that is capable of releasing therapeutic levels of bioactive insulin for several weeks with the potential to stimulate and sustain healing. By encapsulating the crystalline form of insulin within poly(d,l-lactide-co-glycolide) microspheres, we succeeded in stabilizing and then releasing bioactive insulin for up to 25 days. To measure bioactivity we used Rat L6 myofibroblasts, stimulated them with this slow release insulin and determined activation of the receptors on the cell surface by quantifying AKT phosphorylation. There was only a minor and gradual decrease in AKT phosphorylation over time. To determine whether the slow release insulin could stimulate keratinocyte migration, wounding was simulated by scratching confluent cultures of human keratinocytes (HaCaT). Coverage of the scratch "wounds" was significantly faster in the presence of insulin released from microspheres than in the insulin-free control. Extended and sustained topical delivery of active insulin from a stable protein crystal-based reservoir shows promise in promoting tissue healing. PMID:20691251

  12. Enhanced Topical Delivery of Tetrandrine by Ethosomes for Treatment of Arthritis

    PubMed Central

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

    2013-01-01

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

  13. 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

  14. Treatment of Hemophilia A in Utero and Postnatally using Sheep as a Model for Cell and Gene Delivery

    PubMed Central

    Porada, Christopher D.; Almeida-Porada, Graça

    2012-01-01

    Hemophilia A represents the most common inheritable deficiency of the coagulation proteins. Current state-of- the-art treatment consists of frequent prophylactic infusions of plasma-derived or recombinant FVIII protein to maintain hemostasis, and has greatly increased life expectancy and quality of life for many hemophilia A patients. This treatment approach is, however, far from ideal, due to the need for lifelong intravenous infusions, the high treatment cost, and the fact that it is unavailable to a large percentage of the world’s hemophiliacs. There is thus a need for novel treatments that can promise long-term or permanent correction. In contrast to existing protein based therapeutics, gene therapy offers to provide a permanent cure following few, or even a single, treatment. In the present paper, we review ongoing work towards this end, focusing on studies we have performed in a large animal model. Some of the key topics covered in this review include the unique opportunities sheep offer as a model system, the re-establishment and clinical and molecular characterization of a line of sheep with severe hemophilia A, the advantages and feasibility of treating a disease like hemophilia A in utero, and the use of Mesenchymal Stem Cells (MSC) as cellular delivery vehicles for the FVIII gene. The review finishes with a brief discussion of our recent success correcting ovine hemophilia A with a postnatal transplant with gene-modified MSC, and the limitations of this approach that remain to be overcome. PMID:23264887

  15. A column generation approach for evaluating delivery efficiencies of collimator technologies in IMRT treatment planning.

    PubMed

    Gören, M; Taşkin, Z C

    2015-03-01

    Collimator systems used in Intensity Modulated Radiation Therapy can form different geometric aperture shapes depending on their physical capabilities. We compare the efficiency of using regular, rotating and dual multileaf collimator (MLC) systems under different combinations of consecutiveness, interdigitation and rectangular constraints. We also create a virtual freeform collimator, which can form any possible segment shape by opening or closing each bixel independently, to provide a basis for comparison. We formulate the problem of minimizing beam-on time as a large-scale linear programming problem. To deal with its dimensionality, we propose a column generation approach. We demonstrate the efficacy of our approach on a set of clinical problem instances. Our results indicate that the dual MLC under consecutiveness constraint yields very similar beam-on time to a virtual freeform collimator. Our approach also provides a ranking between other collimator technologies in terms of their delivery efficiencies. PMID:25675154

  16. Breast conserving treatment for breast cancer: dosimetric comparison of different non-invasive techniques for additional boost delivery

    PubMed Central

    2014-01-01

    Background Today it is unclear which technique for delivery of an additional boost after whole breast radiotherapy for breast conserved patients should be state of the art. We present a dosimetric comparison of different non-invasive treatment techniques for additional boost delivery. Methods For 10 different tumor bed localizations, 7 different non-invasive treatment plans were made. Dosimetric comparison of PTV-coverage and dose to organs at risk was performed. Results The Vero system achieved an excellent PTV-coverage and at the same time could minimize the dose to the organs at risk with an average near-maximum-dose (D2) to the heart of 0.9 Gy and the average volume of ipsilateral lung receiving 5 Gy (V5) of 1.5%. The TomoTherapy modalities delivered an average D2 to the heart of 0.9 Gy for the rotational and of 2.3 Gy for the static modality and an average V5 to the ipsilateral lung of 7.3% and 2.9% respectively. A rotational technique offers an adequate conformity at the cost of more low dose spread and a larger build-up area. In most cases a 2-field technique showed acceptable PTV-coverage, but a bad conformity. Electrons often delivered a worse PTV-coverage than photons, with the planning requirements achieved only in 2 patients and with an average D2 to the heart of 2.8 Gy and an average V5 to the ipsilateral lung of 5.8%. Conclusions We present advices which can be used as guidelines for the selection of the best individualized treatment. PMID:24467916

  17. Simultaneous Drug and Gene Delivery from the Biodegradable Poly(ε-caprolactone) Nanofibers for the Treatment of Liver Cancer.

    PubMed

    Che, Hui-Lian; Lee, Hwa Jeong; Uto, Koichiro; Ebara, Mitsuhiro; Kim, Won Jong; Aoyagi, Takao; Park, In-Kyu

    2015-10-01

    In this study, we present anti-cancer drug containing nanofiber-mediated gene delivery to treat liver cancer. Electro-spun nanofibers have big potential for local delivery and sustained release of therapeutic gene and drugs. We reported a temperature-responsive nanofibers mainly compounded by branched poly(ε-caprolactone) (PCL) macro-monomers and anti-cancer drug paclitaxel. The nanofiber could be administrated into liver tumors to dramatically hinder their growth and prevent their metastasis. As a result, paclitaxel encapsulated PCL (PTX/PCL) nanofibers with diameters of around several tens nanometers to 10 nm were successfully obtained by electro-spinning and observed in scanning electron microscopy (SEM). Nanoparticles composed of disulfide cross-linked branched PEI (ssPEI) and anti-cancer therapeutic gene miRNA-145 were complexed based on the electrostatic interaction and coated over the paclitaxel-loaded nanofiber. MicroRNA 145/ssPEI nanoparticles (MSNs) immobilized on the PTX/PCL nanofiber showed time-dependent sustained release of the microRNA for enhanced uptake in neighboring liver cancer cells without any noticeable cytotoxicity. From this study we are expecting a synergistic effect on the cancer cell suppression since we have combined the drug and gene delivery. This approach uses the nanofibers and nanoparticles together for the treatment of cancer and the detailed investigation in vitro and in vivo must be conducted for the practicality of this study. The polymer is biodegradable and the toxicity issues must be cleared by our approach. PMID:26726449

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

    PubMed

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

    2014-06-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  20. Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study.

    PubMed

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

    2013-01-01

    The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment. PMID:23527068

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

    SciTech Connect

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

    2010-01-01

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

  2. Fine-tuning vitamin E-containing telodendrimers for efficient delivery of gambogic acid in colon cancer treatment.

    PubMed

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

    2015-04-01

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

  3. Efficacy of transdermal magnesium ascorbyl phosphate delivery after ultrasound treatment with microbubbles in gel-type surrounding medium in mice.

    PubMed

    Liao, Ai-Ho; Lu, Ying-Jui; Hung, Chi-Ray; Yang, Meng-Yu

    2016-04-01

    Liquid microemulsions appropriate for topical application were obtained by increasing their viscosity through the addition of thickening agents. The present study first assessed the usefulness of ultrasound (US) plus US contrast agent, microbubbles (MBs), in agarose gel for enhancing transdermal drug delivery. The effect of US plus MBs in agarose gel on the penetration of the skin by magnesium ascorbyl phosphate (MAP) was explored both in vitro and in vivo. In the in vitro experiments, the stability of MBs was investigated by examining the penetration of MAP by the model drug, Evans blue, in two media: an agarose phantom and pig skin. The penetration depth in the agarose phantom and pig skin increased by 40% and 195%, respectively, when treated with US plus MBs in 0.1% agarose solution combined with MAP (UMB1), and by 48% and 206%, respectively, when treated with US plus MBs in 0.15% agarose solution and MAP (UMB2). The skin-whitening effects in C57BL/6J mice in the UMB1 and UMB2 groups over a 4-week experimental period were significantly increased by 63% and 70%, respectively, in the fourth week. The findings of this study suggest that the survival of MBs with US is affected by the viscosity of the surrounding medium, and that in mice, treatment with US plus MBs in a suitable agarose gel can increase skin permeability and enhance transdermal MAP delivery. PMID:26838887

  4. Delivery of Multiple siRNAs Using Lipid-coated PLGA Nanoparticles for Treatment of Prostate Cancer

    PubMed Central

    Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha; Dunn, Stuart S.; Enlow, Elizabeth M.; Luft, J. Christopher; Tian, Shaomin; Napier, Mary E.; Pohlhaus, Patrick D.; Rolland, Jason P.; DeSimone, Joseph M.

    2012-01-01

    Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called PRINT (Particle Replication In Nonwetting Templates). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32–46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer. PMID:22165988

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

    PubMed

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

    2015-02-10

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

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

    PubMed

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

    2014-09-01

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

  7. An implantable closedloop asynchronous drug delivery system for the treatment of refractory epilepsy.

    PubMed

    Salam, Muhammad Tariqus; Mirzaei, Marjan; Ly, My Sandra; Nguyen, Dang Khoa; Sawan, Mohamad

    2012-07-01

    In this paper, we present an implantable device for intra-cerebral electroencephalography (icEEG) data acquisition and real-time epileptic seizure detection with simultaneous focal antiepileptic drug injection feedback. This implantable device includes a neural signal amplifier, an asynchronous seizure detector, a drug delivery system (DDS) including a micropump, and a hybrid subdural electrode (HSE). The asynchronous detection algorithm is based on data-dependent analysis and validated with Matlab tools. The detector and DDS have a power saving mode. The HSE contacts are made of Platinum (Pt) encapsulated with polydimethylsiloxane (PDMS). Given the heterogeneity of electrographic seizure signals and seizure suppression threshold, the implantable device provides tunable parameters facility through an external transmitter to adapt to each individual's neurophysiology prior to clinical deployment. The proposed detector and DDS were assembled in Ø 50 mm and Ø 30 mm circular printed circuit boards, respectively. The detector was validated using icEEG recordings of seven patients who had previously undergone an intracranial investigation for epilepsy surgery. The triggering of the DDS was tested and a predefined seizure suppression dose was delivered ~16 s after electrographical seizure onsets. The device's power consumption was reduced by 12% in active mode and 49% in power saving mode compared to similar seizure detection algorithms implemented with synchronous architecture. PMID:22491131

  8. A novel and facile synthesis of porous SiO2-coated ultrasmall Se particles as a drug delivery nanoplatform for efficient synergistic treatment of cancer cells

    NASA Astrophysics Data System (ADS)

    Liu, Xijian; Deng, Guoying; Wang, Yeying; Wang, Qian; Gao, Zhifang; Sun, Yangang; Zhang, Wenlong; Lu, Jie; Hu, Junqing

    2016-04-01

    A novel and facile synthetic route has been developed to fabricate porous SiO2-coated ultrasmall Se particles (Se@SiO2 nanospheres) as a drug delivery nanoplatform which combines Se quantum dots and doxorubicin (DOX) for efficient synergistic treatment of cancer cells.A novel and facile synthetic route has been developed to fabricate porous SiO2-coated ultrasmall Se particles (Se@SiO2 nanospheres) as a drug delivery nanoplatform which combines Se quantum dots and doxorubicin (DOX) for efficient synergistic treatment of cancer cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02298g

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

    SciTech Connect

    Fietkau, Rainer . E-mail: rainer.fietkau@med.uni-rostock.de; Roedel, Claus; Hohenberger, Werner; Raab, Rudolf; Hess, Clemens; Liersch, Torsten; Becker, Heinz; Wittekind, Christian; Hutter, Matthias; Hager, Eva; Karstens, Johann; Ewald, Hermann; Christen, Norbert; Jagoditsch, Michael; Martus, Peter; Sauer, Rolf

    2007-03-15

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

  10. A silica-calcium-phosphate nanocomposite drug delivery system for the treatment of hepatocellular carcinoma: in vivo study.

    PubMed

    Swet, Jacob H; Pacheco, Hernando J; Iannitti, David A; El-Ghanam, Ahmed; McKillop, Iain H

    2014-01-01

    Hepatocellular carcinoma (HCC) is notoriously difficult to treat with systemic chemotherapy. The aim of this study was to evaluate a silica-calcium-phosphate nanocomposite (SCPC75) drug delivery system (DDS) as a means to localize cisplatin treatment within the tumor, while reducing systemic toxicity, in a rat model of HCC. The SCPC75 was prepared and loaded with cisplatin and Fourier transform infrared analyses demonstrated even drug distribution within the SCPC75. A rat model of subcutaneous HCC formation was established and animals treated by either systemic cisplatin injection (sCis) or with SCPC75-Cis hybrid placed adjacent (ADJ) to or within (IT) the tumor. Five days after implantation, 50-55% of the total cisplatin loaded had been released from the SCPC75-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared with sCis treatment. sCis-treated animals exhibited severe side effects, including rapid weight loss and decreased liver and kidney function, effects not observed in SCPC75-Cis-treated animals. Analysis of cisplatin distribution demonstrated drug concentrations in the tumor were 21 and 1.5 times higher in IT and ADJ groups, respectively, compared with sCis-treated animals. These data demonstrate the SCPC75 DDS can provide an effective, localized treatment for HCC with significantly reduced toxicity when compared with systemic drug administration. PMID:23913418

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

    PubMed

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

    2015-04-01

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

  12. Fast and accurate Monte Carlo modeling of a kilovoltage X-ray therapy unit using a photon-source approximation for treatment planning in complex media

    PubMed Central

    Zeinali-Rafsanjani, B.; Mosleh-Shirazi, M. A.; Faghihi, R.; Karbasi, S.; Mosalaei, A.

    2015-01-01

    To accurately recompute dose distributions in chest-wall radiotherapy with 120 kVp kilovoltage X-rays, an MCNP4C Monte Carlo model is presented using a fast method that obviates the need to fully model the tube components. To validate the model, half-value layer (HVL), percentage depth doses (PDDs) and beam profiles were measured. Dose measurements were performed for a more complex situation using thermoluminescence dosimeters (TLDs) placed within a Rando phantom. The measured and computed first and second HVLs were 3.8, 10.3 mm Al and 3.8, 10.6 mm Al, respectively. The differences between measured and calculated PDDs and beam profiles in water were within 2 mm/2% for all data points. In the Rando phantom, differences for majority of data points were within 2%. The proposed model offered an approximately 9500-fold reduced run time compared to the conventional full simulation. The acceptable agreement, based on international criteria, between the simulations and the measurements validates the accuracy of the model for its use in treatment planning and radiobiological modeling studies of superficial therapies including chest-wall irradiation using kilovoltage beam. PMID:26170553

  13. Fast and accurate Monte Carlo modeling of a kilovoltage X-ray therapy unit using a photon-source approximation for treatment planning in complex media.

    PubMed

    Zeinali-Rafsanjani, B; Mosleh-Shirazi, M A; Faghihi, R; Karbasi, S; Mosalaei, A

    2015-01-01

    To accurately recompute dose distributions in chest-wall radiotherapy with 120 kVp kilovoltage X-rays, an MCNP4C Monte Carlo model is presented using a fast method that obviates the need to fully model the tube components. To validate the model, half-value layer (HVL), percentage depth doses (PDDs) and beam profiles were measured. Dose measurements were performed for a more complex situation using thermoluminescence dosimeters (TLDs) placed within a Rando phantom. The measured and computed first and second HVLs were 3.8, 10.3 mm Al and 3.8, 10.6 mm Al, respectively. The differences between measured and calculated PDDs and beam profiles in water were within 2 mm/2% for all data points. In the Rando phantom, differences for majority of data points were within 2%. The proposed model offered an approximately 9500-fold reduced run time compared to the conventional full simulation. The acceptable agreement, based on international criteria, between the simulations and the measurements validates the accuracy of the model for its use in treatment planning and radiobiological modeling studies of superficial therapies including chest-wall irradiation using kilovoltage beam. PMID:26170553

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

    PubMed Central

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

    2010-01-01

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

  15. Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain.

    PubMed

    Manda, Prashanth; Kushwaha, Avadhesh Singh; Kundu, Santanu; Shivakumar, H N; Jo, Seong Bong; Murthy, S Narasimha

    2016-02-28

    The purpose of the current study was to investigate the plausibility of delivery of ziconotide to the cerebrospinal fluid (CSF) via intranasal administration. Ziconotide was administered either in the form of solution or Kolliphor P 407 gels (KP 407) intranasally in Sprague-Dawley rats. The effect of incorporation of chitosan in the formulation was also investigated. Time course of drug in the CSF was investigated by collecting CSF from cisterna magna. Pharmacokinetics of ziconotide in CSF following intrathecal and intravenous (i.v.) administration of ziconotide was investigated. Upon intrathecal administration the elimination rate constant of ziconotide in CSF was found to be 1.01±0.34h(-1). The Cmax and Tmax of ziconotide in CSF following intravenous administration were found to be 37.78±6.8ng/mL and ~2h respectively. The time required to attain maximum concentration (Tmax) in CSF was less upon intranasal administration (15min) compared to i.v. administration (120min). Presence of chitosan enhanced the overall bioavailability of ziconotide from intranasal solution and gel formulations. The elimination rate constant of ziconotide in CSF following intranasal and intravenous administration of ziconotide solution was found to be 0.54±0.08h(-1) and 0.42±0.10h(-1) respectively. Whereas, intranasal administration of ziconotide in the form of in situ forming gel lowered the elimination rate significantly. These results suggest that intranasal administration could be a potential noninvasive and patient compliant method of delivering ziconotide to CSF to treat chronic pain. PMID:26732557

  16. Dual drug delivery of tamoxifen and quercetin: Regulated metabolism for anticancer treatment with nanosponges.

    PubMed

    Lockhart, Jacob N; Stevens, David M; Beezer, Dain B; Kravitz, Ariel; Harth, Eva

    2015-12-28

    We report the synthesis and encapsulation of polyester nanosponge particles (NPs) co-loaded with tamoxifen (TAM) and quercetin (QT) to investigate the loading, release and in vitro metabolism of a dual drug formulation. The NPs are made in two variations, 4% and 8% crosslinking densities, to evaluate the effects on metabolism and release kinetics. The NP-4% formulation with a particle size of 89.3 ± 14.8 nm was found to have loading percentages of 6.91 ± 0.13% TAM and 7.72 ± 0.15% QT after targeting 10% (w/w) each. The NP-8% formulation with a particle size of 91.5 ± 9.8 nm was found to have loading percentages of 7.26 ± 0.10% TAM and 7.80 ± 0.12% QT. The stability of the formulation was established in simulated gastrointestinal fluids, and the metabolism of TAM was shown to be reduced 2-fold and 3-fold for NP-4%s and NP-8%s, respectively, while QT metabolism was reduced 3 and 4-fold. The implications for improved bioavailability of the NP formulations were supported by cytotoxicity results that showed a similar efficacy to free dual drug formulations and even enhanced anti-cancer effects in the recovery condition. This work demonstrates the suitability of the nanosponges not only as a dual release drug delivery system but also enabling a regulated metabolism through the capacity of a nanonetwork. The variation in crosslinking enables a dual release with tailored release kinetics and suggests improved bioavailability aided by a reduced metabolism. PMID:26344396

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

    PubMed

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

    2014-06-01

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

  18. Early Intervention and Treatment Acceptability: Multiple Perspectives for Improving Service Delivery in Home Settings.

    ERIC Educational Resources Information Center

    Paget, Kathleen D.

    1991-01-01

    This article examines issues related to treatment acceptability in early intervention programs, by applying concepts pertaining to collaboration, cultural difference, compliance and freedom of choice, family life cycles, and systems theory. A paradigm for designing home-based intervention plans with families of preschoolers with behavior disorders…

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

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Giefer, Eldred E.

    2007-01-01

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

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

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Giefer, Eldred E.

    2007-01-01

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

  1. Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration.

    PubMed

    Lin, Tai-Chi; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Liu, Jorn-Hon; Woung, Lin-Chung; Tsai, Ching-Yao; Chen, Shih-Jen; Chen, Yan-Ting; Hsu, Chih-Chien

    2015-11-01

    Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF) and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration. PMID:26383186

  2. The Delivery and Quality of Sexually Transmitted Infections Treatment by Private General Practitioners in Windhoek Namibia

    PubMed Central

    Iipinge, Scholastika N; Pretorius, Louise

    2012-01-01

    Introduction: The main objective for this study was to investigate the quality of Sexually Transmitted Infections (STI) treatment and control by the private sector in Namibia. Method: This was a cross-sectional study employing quantitative methodology using different methods of data collection. A self-administered questionnaire exploring General Practitioners (GPs) perceptions of factors that influence the way they manage Sexually Transmitted Infections (STI) which was then concluded with the face to face interviews and the checklist that was used while doing observations in the consulting rooms Results: A total of 50 private general practitioners in the area of Windhoek were interviewed, 48 self-administered questionnaires plus all checklists were received back from the private general practitioners. None of the private general practitioners interviewed had specific training in the syndromic management of the STIs. The 86% of all patients were seen by these private general practitioners on a medical aid, while 14 % pay cash for service provided. With regard to Urethral Discharge, an average of 56.5% of GPs could treat urethral discharge correctly as per the Namibian syndromic approach guidelines. None of the GPs could demonstrate the correct treatment of genital ulcer (whether they received medical aid or not) as recommended in the syndromic approach guidelines in Namibia (GRN, 1999; 2000). Only 28% of the GPs could demonstrate the correct treatment of Pelvic Inflammatory Disease (PID) as per the syndromic management of the STIs. For patients without medical aid the drugs prescribed and their dosages for PID are correct but the frequencies are not in line with the guidelines as for patients with medical aid. Discussion: In general, patients presenting with STIs to the GPs in private practices are not given quality of care because not all private general practitioners have time to do investigations, counseling, give condoms and to notify the partners of those with urethral discharge, genital ulcers and PID looking for treatment. PMID:22980389

  3. Biological evaluation of a novel chitosan-PVA-based local delivery system for treatment of periodontitis.

    PubMed

    Wang, Ling Chong; Wu, Hao; Chen, Xi Guang; De Li, Li; Ji, Qiu Xia; Liu, Cheng Sheng; Yu, Le Jun; Ran, Chao; Zhao, Qing Sheng

    2009-12-15

    In the study, we intend to design a suitable localized drug delivery system (LDDS) with chitosan and poly vinyl alcohol (PVA) for treating serve periodontitis. For that, a novel formulation based on the incorporation of chitosan-based microspheres into PVA film was prepared. As the core parts of the novel formulation, chitosan-based microspheres were prepared form chitosan and/or carboxymethyl-chitosan (CM-chitosan) by using water-in-oil emulsification method. Then basic in vitro and in vivo experiments focusing on biocompatibility and biodegradability of the two chitosan-based microspheres were carried out to evaluate the feasibility of the novel LDDS. In vitro tests, besides having no hemolysis, chitosan microsphere (Cs1-Ms), and CM-chitosan microsphere (Cs2-Ms) have adsorbed little proteins on their surfaces. Moreover, plasma proteins adsorbed on Cs2-Ms, most of which can easily desorbed, are much less than that adsorbed on Cs1-Ms. This indicates that Cs2-Ms perhaps has better biocompatibility than Cs1-Ms. In vivo tests, Cs1-Ms and Cs2-Ms were subcutaneously implanted in rat to investigate the host tissue inflammatory response. Implantations of Cs1-Ms and Cs2-Ms induced a little more severe inflammation when compared with the implantation of PVA film. However, the difference on in vivo biocompatibility between Cs1-Ms and Cs2-Ms could not be confirmed by the implantation model of our experiments. Both Cs1-Ms and Cs2-Ms had suffered bioerosion when they were subcutaneously implanted. The hard and compact matrixes of Cs1-Ms were degraded very slowly, and only some trifling degradation had been found until 4 weeks of implantation. In contrast, Cs2-Ms is soft and more hydrophilic, and can be quickly degraded in a form of diffluence by the physiological circumstance. All these results suggested that Cs2-Ms had better potentials used as core parts of the novel designed LDDS in the future developments. PMID:19107793

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

    PubMed

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

    2008-12-01

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

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

    PubMed

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

    2014-11-20

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

  6. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    PubMed Central

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-01-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication. PMID:27090158

  7. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment.

    PubMed

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C L; Chan, Ben; Ng, Frency S F; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C W; Lau, Clara B S; Leung, Ping-Chung

    2016-01-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication. PMID:27090158

  8. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    NASA Astrophysics Data System (ADS)

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-04-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication.

  9. Lactococcus lactis, a tool for the delivery of therapeutic proteins treatment of IBD.

    PubMed

    Steidler, L

    2001-05-11

    Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory diseases that consists of ulcerative colitis (UC), an inflammation of the large intestine, and Crohn's disease (CD), which can affect any part of the gastrointestinal tract. IBD affects approximately 1 in every 1000 individuals in western countries. There is a marked tendency in the age of onset toward gradually younger people. IBD represents a genuine problem in public health because of the absence of etiologic treatment. The clinical image is characterized by recurrent segmental or total inflammatory involvement of the large and/or small intestine, often resulting in a chronic, unpredictable course. The symptoms of both are extremely unpleasant and impact all aspects of quality of life. They include diarrhea, abdominal pain, rectal bleeding, fever, nausea, weight loss, lethargy, and loss of appetite. If left untreated, malnutrition, dehydration, and anemia follow, which, in extreme cases, can even lead to death. Although many patients are managed successfully with conventional medical therapy, such as anti-inflammatory corticosteroid treatment, some stay refractory to treatment, most will have recurrent activity of disease, and two thirds will require surgery. Administered orally or by injection, only a fraction of the active components of most conventional drugs reaches the intended target site, the inflamed intestinal lining. This is not only an inefficient way to deliver drugs, but, more important, means that patients are often subject to a spectrum of unpleasant side effects that result from the high levels of the drugs in other, otherwise healthy tissues and organs of the body. PMID:12805677

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

    NASA Astrophysics Data System (ADS)

    Hamza, Mostafa; Hamza, Mohammad S. E.

    1995-05-01

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

  11. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

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

  12. Combined sonodynamic and antimetabolite therapy for the improved treatment of pancreatic cancer using oxygen loaded microbubbles as a delivery vehicle.

    PubMed

    McEwan, Conor; Kamila, Sukanta; Owen, Joshua; Nesbitt, Heather; Callan, Bridgeen; Borden, Mark; Nomikou, Nikolitsa; Hamoudi, Rifat A; Taylor, Mark A; Stride, Eleanor; McHale, Anthony P; Callan, John F

    2016-02-01

    In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform for the targeted treatment of pancreatic cancer using both sonodynamic therapy (SDT) and antimetabolite therapy. O2MB were prepared with either the sensitiser Rose Bengal (O2MB-RB) or the antimetabolite 5-fluorouracil (O2MB-5FU) attached to the microbubble (MB) surface. The MB were characterised with respect to size, physical stability and oxygen retention. A statistically significant reduction in cell viability was observed when three different pancreatic cancer cell lines (BxPc-3, MIA PaCa-2 and PANC-1), cultured in an anaerobic cabinet, were treated with both SDT and antimetabolite therapy compared to either therapy alone. In addition, a statistically significant reduction in tumour growth was also observed when ectopic human xenograft BxPC-3 tumours in SCID mice were treated with the combined therapy compared to treatment with either therapy alone. These results illustrate not only the potential of combined SDT/antimetabolite therapy as a stand alone treatment option in pancreatic cancer, but also the capability of O2-loaded MBs to deliver O2 to the tumour microenvironment in order to enhance the efficacy of therapies that depend on O2 to mediate their therapeutic effect. Furthermore, the use of MBs to facilitate delivery of O2 as well as the sensitiser/antimetabolite, combined with the possibility to activate the sensitiser using externally applied ultrasound, provides a more targeted approach with improved efficacy and reduced side effects when compared with conventional systemic administration of antimetabolite drugs alone. PMID:26702983

  13. SU-D-16A-04: Accuracy of Treatment Plan TCP and NTCP Values as Determined Via Treatment Course Delivery Simulations

    SciTech Connect

    Siebers, J; Xu, H; Gordon, J

    2014-06-01

    Purpose: To to determine if tumor control probability (TCP) and normal tissue control probability (NTCP) values computed on the treatment planning image are representative of TCP/NTCP distributions resulting from probable positioning variations encountered during external-beam radiotherapy. Methods: We compare TCP/NTCP as typically computed on the planning PTV/OARs with distributions of those parameters computed for CTV/OARs via treatment delivery simulations which include the effect of patient organ deformations for a group of 19 prostate IMRT pseudocases. Planning objectives specified 78 Gy to PTV1=prostate CTV+5 mm margin, 66 Gy to PTV2=seminal vesicles+8 mm margin, and multiple bladder/rectum OAR objectives to achieve typical clinical OAR sparing. TCP were computed using the Poisson Model while NTCPs used the Lyman-Kutcher-Bruman model. For each patient, 1000 30-fraction virtual treatment courses were simulated with each fractional pseudo- time-oftreatment anatomy sampled from a principle component analysis patient deformation model. Dose for each virtual treatment-course was determined via deformable summation of dose from the individual fractions. CTVTCP/ OAR-NTCP values were computed for each treatment course, statistically analyzed, and compared with the planning PTV-TCP/OARNTCP values. Results: Mean TCP from the simulations differed by <1% from planned TCP for 18/19 patients; 1/19 differed by 1.7%. Mean bladder NTCP differed from the planned NTCP by >5% for 12/19 patients and >10% for 4/19 patients. Similarly, mean rectum NTCP differed by >5% for 12/19 patients, >10% for 4/19 patients. Both mean bladder and mean rectum NTCP differed by >5% for 10/19 patients and by >10% for 2/19 patients. For several patients, planned NTCP was less than the minimum or more than the maximum from the treatment course simulations. Conclusion: Treatment course simulations yield TCP values that are similar to planned values, while OAR NTCPs differ significantly, indicating the need for probabilistic methods or PRVs for OAR risk assessment. Presenting author receives support from Philips Medical Systems.

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

    SciTech Connect

    Mail, Noor; Al-Ghamdi, S.; Saoudi, A.; Albarakati, Y.; Ahmad Khan, M.; Saeedi, F.; Safadi, N.

    2013-08-15

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

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

    SciTech Connect

    Harp, Benton J.; Kacich, Richard M.; Skwarek, Raymond J.

    2013-07-01

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

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

    SciTech Connect

    Harp, Benton J.; Kacich, Richard M.; Skwarek, Raymond J.

    2012-12-20

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

  17. Mobile Delivery of Treatment for Alcohol Use Disorders: A Review of the Literature.

    PubMed

    Quanbeck, Andrew; Chih, Ming-Yuan; Isham, Andrew; 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

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

    SciTech Connect

    Wheeler, F.J.; Nigg, D.W.; Capala, J.

    1997-10-01

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

  19. Pharmacological consequences of inhaled drug delivery to small airways in the treatment of asthma.

    PubMed

    Bodzenta-Łukaszyk, Anna; Kokot, Marek

    2014-08-01

    Small peripheral airways are an important target for the anti-inflammatory treatment of asthma. To make anti-inflammatory drugs (inhaled corticosteroids [ICS]) effectively reach small airways, they should be delivered using inhalation techniques containing high proportions of fine or super-fine particles. Higher proportions of fine particles are associated with higher systemic absorption of ICS leading to an increased risk of endogenous cortisol suppression. Ciclesonide, despite the highest proportion of fine and super-fine particle fractions, is the only ICS not associated with an increased risk of systemic adverse effects, including cortisol suppression. In contrary to ICS, bronchodilators should not be administered to peripheral airways. This does not improve their efficacy and may increase their risk of cardiotoxicity. Thus, from a pharmacological point of view and the theory of aerosols' deposition, fixed combinations of ICS and long-acting beta agonists are always suboptimal. In many cases, the best solution may be to use fine-particle ciclesonide and a non-fine particle beta agonist administered from separate inhalers. PMID:25116888

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

    PubMed

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

    2015-02-20

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

  1. Skeletal Muscle in Motor Neuron Diseases: Therapeutic Target and Delivery Route for Potential Treatments

    PubMed Central

    Dupuis, Luc; Echaniz-Laguna, Andoni

    2010-01-01

    Lower motor neuron (LMN) degeneration occurs in several diseases that affect patients from neonates to elderly and can either be genetically transmitted or occur sporadically. Among diseases involving LMN degeneration, spinal muscular atrophy (SMA) and spinal bulbar muscular atrophy (Kennedy’s disease, SBMA) are pure genetic diseases linked to loss of the SMN gene (SMA) or expansion of a polyglutamine tract in the androgen receptor gene (SBMA) while amyotrophic lateral sclerosis (ALS) can either be of genetic origin or occur sporadically. In this review, our aim is to put forward the hypothesis that muscle fiber atrophy and weakness might not be a simple collateral damage of LMN degeneration, but instead that muscle fibers may be the site of crucial pathogenic events in these diseases. In SMA, the SMN gene was shown to be required for muscle structure and strength as well as for neuromuscular junction formation, and a subset of SMA patients develop myopathic pathology. In SBMA, the occurence of myopathic histopathology in patients and animal models, along with neuromuscular phenotype of animal models expressing the androgen receptor in muscle only has lead to the proposal that SBMA may indeed be a muscle disease. Lastly, in ALS, at least part of the phenotype might be explained by pathogenic events occuring in skeletal muscle. Apart from its potential pathogenic role, skeletal muscle pathophysiological events might be a target for treatments and/or be a preferential route for targeting motor neurons. PMID:20840067

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

    PubMed Central

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

    2011-01-01

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

  3. Molecular target validation, antimicrobial delivery, and potential treatment of Toxoplasma gondii infections

    PubMed Central

    Lai, Bo-Shiun; Witola, William H.; El Bissati, Kamal; Zhou, Ying; Mui, Ernest; Fomovska, Alina; McLeod, Rima

    2012-01-01

    Toxoplasma gondii persistently infects over two billion people worldwide. It can cause substantial morbidity and mortality. Existing treatments have associated toxicities and hypersensitivity and do not eliminate encysted bradyzoites that recrudesce. New, improved medicines are needed. Transductive peptides carry small molecule cargos across multiple membranes to enter intracellular tachyzoites and encysted bradyzoites. They also carry cargos into retina when applied topically to eyes, and cross blood brain barrier when administered intravenously. Phosphorodiamidate morpholino oligomers (PMO) inhibit gene expression in a sequence-specific manner. Herein, effect of transductive peptide conjugated PMO (PPMO) on tachyzoite protein expression and replication in vitro and in vivo was studied. Initially, sequence-specific PPMO successfully reduced transfected T. gondii’s fluorescence and luminescence. PPMO directed against T. gondii’s dihydrofolate reductase (DHFR), an enzyme necessary for folate synthesis, limited tachyzoite replication. Rescue with exogenous folate demonstrated DHFR PPMO‘s specificity. PPMO directed against enoyl-ACP reductase (ENR), an enzyme of type II fatty acid synthesis that is structurally distinct in T. gondii from ENR in mammalian cells was investigated. PPMO directed against plant-like Apetela 2 (AP2) domain transcription factor XI-3 (AP2XI-3), not present in human cells, was characterized. ENR and AP2XI-3 PPMO each restricted intracellular parasite replication validating these molecular targets in tachyzoites. DHFR-specific PPMO administered to infected mice diminished parasite burden. Thus, these antisense oligomers are a versatile approach to validate T. gondii molecular targets, reduce essential T. gondii proteins in vitro and in vivo, and have potential for development as curative medicines. PMID:22891343

  4. Sci—Thur PM: Planning and Delivery — 06: Real-Time Interactive Treatment Planning

    SciTech Connect

    Matthews, Q; Mestrovic, A; Otto, K

    2014-08-15

    Purpose: To describe and evaluate a novel system for generalized Real-Time Interactive Planning (RTIP) applied to head and neck (H and N) VMAT. Methods: The clinician interactively manipulates dose distributions using DVHs, isodoses, or rate of dose fall-off, which may be subjected to user-defined constraints. Dose is calculated using a fast Achievable Dose Estimate (ADE) algorithm, which simulates the limits of what can be achieved during treatment. After each manipulation contributing fluence elements are modified and the dose distribution updates in effectively real-time. For H and N VMAT planning, structure sets for 11 patients were imported into RTIP. Each dose distribution was interactively modified to minimize OAR dose while constraining target DVHs. The resulting RTIP DVHs were transferred to the Eclipse™ VMAT optimizer, and conventional VMAT optimization was performed. Results: Dose calculation and update times for the ADE algorithm ranged from 2.4 to 22.6 milliseconds, thus facilitating effectively real-time manipulation of dose distributions. For each of the 11 H and N VMAT cases, the RTIP process took ∼2–10 minutes. All RTIP plans exhibited acceptable PTV coverage, mean dose, and max dose. 10 of 11 RTIP plans achieved substantially improved sparing of one or more OARs without compromising dose to targets or other OARs. Importantly, 10 of the 11 RTIP plans required only one or two post-RTIP optimizations. Conclusions: RTIP is a novel system for manipulating and updating achievable dose distributions in real-time. H and N VMAT plans generated using RTIP demonstrate improved OAR sparing and planning efficiency. Disclosures: One author has a commercial interest in the presented materials.

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

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

    PubMed Central

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

    2014-01-01

    Background: Amphotericin B (AmB) is among the gold standard antifungal agents used for the treatment of the wide range of fungal infections. However, the drug has various side- effects. Transdermal approach for the delivery of drug is one of the accepted and convenient modes of drug delivery. Aim: The current work was designed to formulate and to evaluate the AmB emulgel system. Materials and Methods: In the preparation of AmB emulgel, Carbopol 930 was used as a gel in this study. The formulation was evaluated for viscosity, spreadability, drug content, drug release and in vitro and in vivo antifungal testing. Results: AmB emulgel was found to penetrate skin effectively and without any irritation. Further, in vivo studies revealed effective therapeutic potential against Candida albicans induced dermal mycosis. Conclusions: The current work, for the first time, revealed effective delivery of AmB across the skin. PMID:25071257

  7. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse

    PubMed Central

    Liu, Yuchen; Li, Dameng; Liu, Zhengya; Zhou, Yu; Chu, Danping; Li, Xihan; Jiang, Xiaohong; Hou, Dongxia; Chen, Xi; Chen, Yuda; Yang, Zhanzhao; Jin, Ling; Jiang, Waner; Tian, Chenfei; Zhou, Geyu; Zen, Ke; Zhang, Junfeng; Zhang, Yujing; Li, Jing; Zhang, Chen-Yu

    2015-01-01

    Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools. In the present study, we employed modified exosomes expressing the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface to deliver opioid receptor mu (MOR) siRNA into the brain to treat morphine addiction. We found that MOR siRNA could be efficiently packaged into RVG exosomes and was associated with argonaute 2 (AGO2) in exosomes. These exosomes efficiently and specifically delivered MOR siRNA into Neuro2A cells and the mouse brain. Functionally, siRNA-loaded RVG exosomes significantly reduced MOR mRNA and protein levels. Surprisingly, MOR siRNA delivered by the RVG exosomes strongly inhibited morphine relapse via the down-regulation of MOR expression levels. In conclusion, our results demonstrate that targeted RVG exosomes can efficiently transfer siRNA to the central nervous system and mediate the treatment of morphine relapse by down-regulating MOR expression levels. Our study provides a brand new strategy to treat drug relapse and diseases of the central nervous system. PMID:26633001

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

    PubMed

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

    2014-03-25

    In this paper, we report the synthesis, characterization (FT-IR, XRD, BET, HR-TEM) and bioevaluation of a novel γ-aminobutiric acid/silica (noted GABA-SiO₂ or γ-SiO₂) hybrid nanostructure, for the improved release of topical antibiotics, used in the treatment of Staphylococcus aureus infections. GABA-SiO₂ showed IR bands which were assigned to Si-O-Si (stretch mode). The XRD pattern showed a broad peak in the range of 18-30° (2θ), indicating an amorphous structure. Based on the BET analysis, estimations about surface area (438.14 m²/g) and pore diameters (4.76 nm) were done. TEM observation reveals that the prepared structure presented homogeneity and an average size of particles not exceeding 10nm. The prepared nanostructure has significantly improved the anti-staphylococcal activity of bacitracin and kanamycin sulfate, as demonstrated by the drastic decrease of the minimal inhibitory concentration of the respective antibiotics loaded in the GABA-SiO₂ nanostructure. These results, correlated with the high biocompatibility of this porous structure, are highlighting the possibility of using this carrier for the local delivery of the antimicrobial substances in lower active doses, thus reducing their cytotoxicity and side-effects. PMID:23871740

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

    PubMed

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

    2011-11-01

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

  10. Fentanyl buccal tablet for the treatment of breakthrough pain: pharmacokinetics of buccal mucosa delivery and clinical efficacy.

    PubMed

    Darwish, Mona; Hamed, Ehab; Messina, John

    2010-01-01

    The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA((R)), Cephalon, Inc.) employs OraVescent((R)) drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP. PMID:20634985

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

    PubMed

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

    2015-02-18

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    Gidwani, Bina; Vyas, Amber

    2016-03-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Formulation development and optimization of transungual drug delivery system of terbinafine hydrochloride for the treatment of onychomycosis.

    PubMed

    Patel, Mayur M; Vora, Zeal M

    2016-06-01

    The aim of present investigation was to develop transungual drug delivery system (nail lacquer) of terbinafine hydrochloride for treatment of onychomycosis. Different types of penetration enhancers, viz. 2-mercaptoethanol, n-acetyl-L-cysteine and thioglycolic acid, were evaluated to determine their effect on drug permeation. Various types of polymers, both hydrophobic (Eudragit® RL 100 and Eudragit® RS 100) and hydrophilic polymers (hydroxypropyl methyl cellulose (HPMC) E15), were evaluated for their film-forming and drug permeation characteristics. The nail lacquer was optimised statistically by applying 3(2) full factorial design. Polymer ratio (Eudragit® RL 100/HPMC E15; X 1) and solvent ratio (ethanol/water; X 2) were selected as independent variable, and viscosity (cPs), nail plate hydration (%) and in vitro drug permeated at the end of 24 h (μg/cm(2)) were selected as dependent variable. The optimised batch comprises of polymer ratio (70:30) and solvent ratio (75:25). Ex vivo drug permeation study was performed using human cadaver toe nail plate. The results revealed that the amount of drug permeated at the end of 24 h was 61.55 ± 3.2 μg/cm(2), which was found to be higher than the minimum inhibitory concentration of drug. This study confirms that the developed drug-loaded nail lacquer could be used as a promising tool for the effective treatment of onychomycosis. PMID:26926242

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

    PubMed

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

    2014-01-01

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

  18. Control Point Analysis comparison for 3 different treatment planning and delivery complexity levels using a commercial 3-dimensional diode array

    SciTech Connect

    Abdellatif, Ady; Gaede, Stewart

    2014-07-01

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

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

    PubMed

    Abdellatif, Ady; Gaede, Stewart

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

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

    PubMed

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

    2012-01-01

    Cervical cancer remains a major problem in women's health worldwide. In this research, a novel biodegradable d-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA)) nanoparticle (NP) was developed as a co-delivery system of docetaxel and endostatin for the synergistic treatment of cervical cancer. Docetaxel-loaded TPGS-b-(PCL-ran-PGA) NPs were prepared and further modified by polyethyleneimine for coating plasmid pShuttle2-endostatin. All NPs were characterized in size, surface charge, morphology, and in vitro release of docetaxel and pDNA. The uptake of coumarin 6-loaded TPGS-b-(PCL-ran-PGA)/PEI-pDsRED by HeLa cells was observed via fluorescent microscopy and confocal laser scanning microscopy. Endostatin expression in HeLa cells transfected by TPGS-b-(PCL-ran-PGA)/PEI-pShuttle2-endostatin NPs was detected using Western blot analysis, and the cell viability of different NP-treated HeLa cells was determined by MTT assay. The HeLa cells from the tumor model, nude mice, were treated with various NPs including docetaxel-loaded-TPGS-b-(PCL-ran-PGA)/PEI-endostatin NPs, and their survival time, tumor volume and body weight were monitored during regimen process. The tumor tissue histopathology was analyzed using hematoxylin and eosin staining, and microvessel density in tumor tissue was evaluated immunohistochemically. The results showed that the TPGS-b-(PCL-ran-PGA)/PEI NPs can efficiently and simultaneously deliver both coumarin-6 and plasmids into HeLa cells, and the expression of endostatin was verified via Western blot analysis. Compared with control groups, the TPGS-b-(PCL-ran-PGA)/PEI-pShuttle2-endostatin NPs significantly decreased the cell viability of HeLa cells (p < 0.01), inhibited the growth of tumors, and even eradicated the tumors. The underlying mechanism is attributed to synergistic anti-tumor effects by the combined use of docetaxel, endostatin, and TPGS released from NPs. The TPGS-b-(PCL-ran-PGA) NPs could function as multifunctional carrier for chemotherapeutic drugs and genetic material delivery, and offer considerable potential as an ideal candidate for in vivo cancer therapy. PMID:23216701

  2. A fully electronic intensity-modulated radiation therapy quality assurance (IMRT QA) process implemented in a network comprised of independent treatment planning, record and verify, and delivery systems

    PubMed Central

    Bailey, Daniel W; Kumaraswamy, Lalith; Podgorsak, Matthew B

    2010-01-01

    Background The purpose of this study is to implement an electronic method to perform and analyze intensity-modulated radiation therapy quality assurance (IMRT QA) using an aSi megavoltage electronic portal imaging device in a network comprised of independent treatment planning, record and verify (R&V), and delivery systems. Methods A verification plan was generated in the treatment planning system using the actual treatment plan of a patient. After exporting the treatment fields to the R&V system, the fields were delivered in QA mode with the aSi imager deployed. The resulting dosimetric images are automatically stored in a DICOM-RT format in the delivery system treatment console computer. The relative dose density images are subsequently pushed to the R&V system. The absolute dose images are then transferred electronically from the treatment console computer to the treatment planning system and imported into the verification plan in the dosimetry work space for further analysis. Screen shots of the gamma evaluation and isodose comparison are imported into the R&V system as an electronic file (e.g. PDF) to be reviewed prior to initiation of patient treatment. A relative dose image predicted by the treatment planning system can also be sent to the R&V system to be compared with the relative dose density image measured with the aSi imager. Results Our department does not have integrated planning, R&V, and delivery systems. In spite of this, we are able to fully implement a paperless and filmless IMRT QA process, allowing subsequent analysis and approval to be more efficient, while the QA document is directly attached to its specific patient chart in the R&V system in electronic form. The calculated and measured relative dose images can be compared electronically within the R&V system to analyze the density differences and ensure proper dose delivery to patients. Conclusions In the absence of an integrated planning, verifying, and delivery system, we have shown that it is nevertheless possible to develop a completely electronic IMRT QA process. PMID:22933903

  3. Current strategies for targeted delivery of bio-active drug molecules in the treatment of brain tumor.

    PubMed

    Garg, Tarun; Bhandari, Saurav; Rath, Goutam; Goyal, Amit K

    2015-12-01

    Brain tumor is one of the most challenging diseases to treat. The major obstacle in the specific drug delivery to brain is blood-brain barrier (BBB). Mostly available anti-cancer drugs are large hydrophobic molecules which have limited permeability via BBB. Therefore, it is clear that the protective barriers confining the passage of the foreign particles into the brain are the main impediment for the brain drug delivery. Hence, the major challenge in drug development and delivery for the neurological diseases is to design non-invasive nanocarrier systems that can assist controlled and targeted drug delivery to the specific regions of the brain. In this review article, our major focus to treat brain tumor by study numerous strategies includes intracerebral implants, BBB disruption, intraventricular infusion, convection-enhanced delivery, intra-arterial drug delivery, intrathecal drug delivery, injection, catheters, pumps, microdialysis, RNA interference, antisense therapy, gene therapy, monoclonal/cationic antibodies conjugate, endogenous transporters, lipophilic analogues, prodrugs, efflux transporters, direct conjugation of antitumor drugs, direct targeting of liposomes, nanoparticles, solid-lipid nanoparticles, polymeric micelles, dendrimers and albumin-based drug carriers. PMID:25835469

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

    PubMed

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

    2004-01-01

    Salicylic acid (SA) is a beta hydroxy acid and has multifunctional uses in the treatment of various diseases in skin such as acne, psoriasis, and photoaging. One problem often cited as associated with salicylic acid is that it can be quite irritating at pH 3-4, where it exhibits the highest activity in the treatment of skin diseases. We have identified strategies to control the irritation potential of salicylic acid formulations and have focused on hydroalcoholic solutions used in acne wipes. One strategy is to control the penetration of SA into the skin. Penetration of the drug into various layers of skin, i.e., epidermis, dermis, and receptor fluid, was measured using a modified Franz in vitro diffusion method after various exposure times up to 24 hours. A polyurethane polymer (polyolprepolymer-15) was found to be an effective agent in controlling delivery of SA. In a dose-dependent fashion it targeted delivery of more SA to the epidermis as compared to penetration through the skin into the receptor fluid. It also reduced the rapid rate of permeation of a large dose of SA through the skin in the first few hours of exposure. A second strategy that proved successful was incorporation of known mild nonionic surfactants like isoceteth-20. These surfactants cleanse the skin, yet due to their inherent mildness (because of their reduced critical micelle concentration and monomer concentration), keep the barrier intact. Also, they reduce the rate of salicylic acid penetration, presumably through micellar entrapment (either in solution or on the skin surface after the alcohol evaporates). Cumulative irritation studies showed that targeting delivery of SA to the epidermis and reducing the rapid early rate of penetration of large amounts of drug through the skin resulted in a reduced irritation potential. In vivo irritation studies also showed that the surfactant system is the most important factor controlling irritancy. SA delivery is secondary, as formulations with less SA content reduced the rate of delivery to the receptor and yet were some of the most irritating formulations tested, presumably due to the action of the specific anionic surfactant on the barrier. Alcohol content also did not appreciably affect irritation and SA delivery; formulations with considerably lower alcohol content but containing anionic versus nonionic surfactant systems exhibited considerably higher irritancy. Thus the surfactant type was again the predominant factor in those studies, although arguably alcohol plays some role (solubilization of SA). Results showed that both polymers and mild surfactants work in concert to provide the optimal formulation benefits of targeted delivery and reduced irritation. Synergistic relationships among hydroalcoholic formulation components will be discussed along with the mechanisms likely involved in controlling delivery of SA to skin. PMID:15037921

  5. A three-drug nanoscale drug delivery system designed for preferential lymphatic uptake for the treatment of metastatic melanoma.

    PubMed

    Doddapaneni, Bhuvana S; Kyryachenko, Sergiy; Chagani, Sharmeen E; Alany, Raid G; Rao, Deepa A; Indra, Arup K; Alani, Adam W G

    2015-12-28

    Metastatic melanoma has a high mortality rate due to lymphatic progression of the disease. Current treatment is surgery followed by radiation and intravenous chemotherapy. However, drawbacks for current chemotherapeutics lie in the fact that they develop resistance and do not achieve therapeutic concentrations in the lymphatic system. We hypothesize that a three-drug nanoscale drug delivery system, tailored for lymphatic uptake, administered subcutaneously, will have decreased drug resistance and therefore offer better therapeutic outcomes. We prepared and characterized nanoparticles (NPs) with docetaxel, everolimus, and LY294002 in polyethyleneglycol-block-poly(ε-caprolactone) (PEG-PCL) polymer with different charge distributions by modifying the ratio of anionic and neutral end groups on the PEG block. These NPs are similarly sized (~48 nm), with neutral, partially charged, or fully charged surface. The NPs are able to load ~2mg/mL of each drug and are stable for 24h. The NPs are assessed for safety and efficacy in two transgenic metastatic melanoma mouse models. All the NPs were safe in both models based on general appearance, weight changes, death, and blood biochemical analyses. The partially charged NPs are most effective in decreasing the number of melanocytes at both the proximal (sentinel) lymph node (LN) and the distal LN from the injection site. The neutral NPs are efficacious at the proximal LN, while the fully charged NPs have no effect on either LNs. Thus, our data indicates that the NP surface charge and lymphatic efficacy are closely tied to each other and the partially charged NPs have the highest potential in treating metastatic melanoma. PMID:26578440

  6. Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice.

    PubMed

    Su, Jin; Sherman, Alexandra; Doerfler, Phillip A; Byrne, Barry J; Herzog, Roland W; Daniell, Henry

    2015-10-01

    Deficiency of acid alpha glucosidase (GAA) causes Pompe disease in which the patients systemically accumulate lysosomal glycogen in muscles and nervous systems, often resulting in infant mortality. Although enzyme replacement therapy (ERT) is effective in treating patients with Pompe disease, formation of antibodies against rhGAA complicates treatment. In this report, we investigated induction of tolerance by oral administration of GAA expressed in chloroplasts. Because full-length GAA could not be expressed, N-terminal 410-amino acids of GAA (as determined by T-cell epitope mapping) were fused with the transmucosal carrier CTB. Tobacco transplastomic lines expressing CTB-GAA were generated through site-specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low-level expression of CTB-GAA in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of GAA to a chloroplast protein that has homology to mannose-6 phosphate receptor. Oral administration of the plant-made CTB-GAA fusion protein even at 330-fold lower dose (1.5 μg) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 μg rhGAA per dose, with several-fold lower titre of GAA-specific IgG1 and IgG2a. Lyophilization increased CTB-GAA concentration by 30-fold (up to 190 μg per g of freeze-dried leaf material), facilitating long-term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in ERT for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or in vitro propagation. PMID:26053072

  7. Provision of Palliative Care in Low- and Middle-Income Countries: Overcoming Obstacles for Effective Treatment Delivery.

    PubMed

    Hannon, Breffni; Zimmermann, Camilla; Knaul, Felicia M; Powell, Richard A; Mwangi-Powell, Faith N; Rodin, Gary

    2016-01-01

    Despite being declared a basic human right, access to adult and pediatric palliative care for millions of individuals in need in low- and middle-income countries (LMICs) continues to be limited or absent. The requirement to make palliative care available to patients with cancer is increasingly urgent because global cancer case prevalence is anticipated to double over the next two decades. Fifty percent of these cancers are expected to occur in LMICs, where mortality figures are disproportionately greater as a result of late detection of disease and insufficient access to appropriate treatment options. Notable initiatives in many LMICs have greatly improved access to palliative care. These can serve as development models for service scale-up in these regions, based on rigorous evaluation in the context of specific health systems. However, a multipronged public health approach is needed to fulfill the humane and ethical obligation to make palliative care universally available. This includes health policy that supports the integration of palliative care and investment in systems of health care delivery; changes in legislation and regulation that inappropriately restrict access to opioid medications for individuals with life-limiting illnesses; education and training of health professionals; development of a methodologically rigorous data and research base specific to LMICs that encompasses health systems and clinical care; and shifts in societal and health professional attitudes to palliative and end-of-life care. International partnerships are valuable to achieve these goals, particularly in education and research, but leadership and health systems stewardship within LMICs are critical factors that will drive and implement change. PMID:26578612

  8. Lycopodium clavatum exine microcapsules enable safe oral delivery of 3,4-diaminopyridine for treatment of botulinum neurotoxin A intoxication.

    PubMed

    Harris, T L; Wenthur, C J; Diego-Taboada, A; Mackenzie, G; Corbitt, T S; Janda, K D

    2016-03-01

    3,4-Diaminopyridine has shown promise in reversing botulinum intoxication, but poor pharmacokinetics and a narrow therapeutic window limit its clinical utility. Thus, we developed a pH-dependent oral delivery platform using club moss spore exines. These exine microcapsules slowed 3,4-diaminopyridine absorption, limited its seizure activity, and enabled delivery of doses which prolonged mouse survival after botulism neurotoxin A intoxication. PMID:26906286

  9. Combined Treatment with Systemic and Local Delivery of Substance P Coupled with Self-Assembled Peptides for a Hind Limb Ischemia Model.

    PubMed

    Kim, Ji Eun; Jung, Ki Moon; Kim, Soo Hyun; Jung, Youngmee

    2016-03-01

    When treating critical limb ischemia caused by various chronic diseases such as diabetes and hypertension, it is essential to effectively induce angiogenesis to supply blood flow to the ischemic region. Recently, several studies have investigated the effects of cell transplantation with mesenchymal stem cells (MSCs) as a therapeutic modality for treating these ischemic diseases. However, some limitations have to be overcome first before cell transplantation can be considered as a promising treatment for ischemic diseases, such as limited sources of cells and the low survival rates of transplanted cells. In this study, self-assembled peptide (SAP) hydrogels coupled with substance P (SP) were used to induce the recruitment of MSCs in an injury site in mouse ischemic hind limb models without exogenous injection of cells. In addition, a combined delivery strategy consisting of local and systemic delivery of SP was used to examine the synergetic effects of systemic and local deliveries. Limb ischemia in athymic mice was induced through the femoral artery by ligating and resecting its branches, and SAP coupled with SP (bioactive SAPs) was injected into the ischemic region. The therapeutic effects on the ischemic region were observed in terms of cell migration, fibrosis, apoptosis, and angiogenesis in each experimental group. The combined therapeutic delivery system resulted in the recruitment of more cells for effective regeneration, promotion of neovascularization, and formation of mature vessels for tissue perfusion and inhibition of fibrosis and cell apoptosis than a single treatment. In conclusion, it was confirmed that the combined therapy of local and system delivery of the SP-conjugated peptide hydrogels and SP could effectively enhance the mobilization of host cells related to angiogenesis to injured tissue, and consequently, they could be useful in treating ischemic diseases without cell transplantation. PMID:26873410

  10. Effect of Repeated Treatment of Pregnant Women with Sulfadoxine-Pyrimethamine and Azithromycin on Preterm Delivery in Malawi: A Randomized Controlled Trial

    PubMed Central

    Luntamo, Mari; Kulmala, Teija; Mbewe, Bernard; Cheung, Yin Bun; Maleta, Kenneth; Ashorn, Per

    2010-01-01

    Preterm delivery, which is associated with infections during pregnancy, is common in sub-Saharan Africa. We enrolled 1,320 pregnant women into a randomized, controlled trial in Malawi to study whether preterm delivery and low birth weight (LBW) incidence can be reduced by intermittent preventive treatment of maternal malaria and reproductive tract infections. The participants received either sulfadoxine-pyrimethamine (SP) twice (controls), monthly SP, or monthly SP and two doses of azithromycin (AZI-SP). The incidence of preterm delivery was 17.9% in controls, 15.4% in the monthly SP group (P = 0.32), and 11.8% in AZI-SP group (risk ratio = 0.66, P = 0.01). Compared with controls, those in AZI-SP group had a risk ratio of 0.61 (P = 0.02) for LBW. Incidence of serious adverse events was low in all groups. In conclusion, the incidence of preterm delivery and LBW can in some conditions be reduced by treating pregnant women with monthly SP and two azithromycin doses. PMID:21118924

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

    PubMed Central

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

    2014-01-01

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

  12. Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Burke, Caitlin W.; Price, Richard J.

    2010-01-01

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

  14. Slow-release drug delivery through Elvax 40W to the rat retina: implications for the treatment of chronic conditions.

    PubMed

    Fiorani, Lavinia; Maccarone, Rita; Fernando, Nilisha; Colecchi, Linda; Bisti, Silvia; Valter, Krisztina

    2014-01-01

    Diseases of the retina are difficult to treat as the retina lies deep within the eye. Invasive methods of drug delivery are often needed to treat these diseases. Chronic retinal diseases such as retinal oedema or neovascularization usually require multiple intraocular injections to effectively treat the condition. However, the risks associated with these injections increase with repeated delivery of the drug. Therefore, alternative delivery methods need to be established in order to minimize the risks of reinjection. Several other investigations have developed methods to deliver drugs over extended time, through materials capable of releasing chemicals slowly into the eye. In this investigation, we outline the use of Elvax 40W, a copolymer resin, to act as a vehicle for drug delivery to the adult rat retina. The resin is made and loaded with the drug. The drug-resin complex is then implanted into the vitreous cavity, where it will slowly release the drug over time. This method was tested using 2-amino-4-phosphonobutyrate (APB), a glutamate analogue that blocks the light response of the retina. It was demonstrated that the APB was slowly released from the resin, and was able to block the retinal response by 7 days after implantation. This indicates that slow-release drug delivery using this copolymer resin is effective for treating the retina, and could be used therapeutically with further testing. PMID:25286223

  15. Drug delivery systems.

    PubMed

    Robinson, D H; Mauger, J W

    1991-10-01

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

  16. Photo-activatable ternary complex based on a multifunctional shielding material for targeted shRNA delivery in cancer treatment.

    PubMed

    Park, Sin-Jung; Park, Wooram; Na, Kun

    2013-11-01

    A photo-activatable ternary complex (PTC) consisting of multifunctional shielding material (MSM) with photosensitizer (PS)-conjugated chondroitin sulfate and polyethyleneimine based binary complexes containing epidermal growth factor receptor (EGFR)-shRNA delivery for CD44 targeted cancer therapy has been developed. The PTC has a negative surface charge of -37.9 mV, and a size of approximately 90 nm, and the ternary complexes were found to be stable against plasma proteins. The stable nanostructure of PTC especially could enable CD44-receptor mediated tumor-targeted delivery and PS-mediated endosomal disruption for efficient gene silencing, and an enhanced rate of cancer cell death was achieved both in vitro and in vivo. This suggests that PTC could represent a promising strategy for the delivery of other therapeutic genes for cancer therapy. PMID:23968856

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

    PubMed Central

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

    2014-01-01

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

  18. Synchronized delivery of Er:YAG-laser pulses into water studied by a laser beam transmission probe for enhanced endodontic treatment

    NASA Astrophysics Data System (ADS)

    Gregorčič, P.; Lukač, N.; Možina, J.; Jezeršek, M.

    2016-04-01

    We examine the effects of the synchronized delivery of multiple Er:YAG-laser pulses during vapor-bubble oscillations into water. For this purpose, we used a laser beam transmission probe that enables monitoring of the bubble's dynamics from a single shot. To overcome the main drawbacks of this technique, we propose and develop an appropriate and robust calibration by simultaneous employment of shadow photography. By using the developed experimental method, we show that the resonance effect is obtained when the second laser pulse is delivered at the end or slightly after the first bubble's collapse. In this case, the resonance effect increases the mechanical energy of the secondary bubble's oscillations and prolongs their duration. The presented laser method for synchronized delivery of Er:YAG-laser pulses during bubble oscillations has great potential for further improvement of laser endodontic treatment, especially upon their safety and efficiency.

  19. Concurrent sequencing of full-dose CMF chemotherapy and radiation therapy in early breast cancer has no effect on treatment delivery.

    PubMed

    Faul, C; Brufsky, A; Gerszten, K; Flickinger, J; Kunschner, A; Jacob, H; Vogel, V

    2003-04-01

    With the increasing use of breast-conserving therapy plus systemic chemotherapy for the treatment of early breast cancer, the optimal sequencing of radiation therapy and chemotherapy remains controversial. Sequencing of therapy may influence not only treatment delivery, but control rates, complications and cosmesis. The aim of this study was to evaluate whether concurrent sequencing of standard doses of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) and adjuvant radiation therapy for early breast cancer impacted on optimum treatment delivery. As both an intravenous (i.v.) 3-week regimen and classic (standard) CMF were utilised in this study, both types of CMF were compared. The effect of sequencing on complications and treatment delays were also assessed. 116 patients treated with CMF chemotherapy and adjuvant tangent breast radiation were studied. 73 patients were treated prospectively with concurrent therapy and were retrospectively compared with a matched group of 40 patients treated with sequential or sandwich therapy. All patients had stage 1 or 2 cancers. There were no planned dose reductions introduced for either treatment modality. Concurrent sequencing had no impact on the ability to deliver optimum radiation or chemotherapy doses. There was no significant difference in acute Radiation Therapy Oncology Group (RTOG) skin reactions or complications between the two groups. Although small, there was a significant delay (1.32 days (0-15 versus 0.36 (0-7)) in the concurrent group (P=0.03) in the delivery of radiation therapy. Sequencing had no significant effect on haematological parameters. 'Standard' CMF had a more profound effect on treatment delivery than i.v. CMF (Radiation delay 2.2 days versus 0.26, P=0.002, % chemotherapy delivered 93% versus 99% P=0.000004). At a mean follow-up of 2.6 years, there was no difference in the cosmetic scores between the two groups. Both local and distant control rates were excellent. This study has shown that standard radiation therapy can be delivered safely concurrently with CMF chemotherapy. Whether this approach may lead to better control rates in the future needs further study. PMID:12651201

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

    NASA Astrophysics Data System (ADS)

    Knežević, Nikola Ž.; Lin, Victor S.-Y.

    2013-01-01

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

  1. Treatment approach, delivery, and follow-up evaluation for cardiac rhythm disease management patients receiving radiation therapy: Retrospective physician surveys including chart reviews at numerous centers

    SciTech Connect

    Gossman, Michael S.; Wilkinson, Jeffrey D.; Mallick, Avishek

    2014-01-01

    In a 2-part study, we first examined the results of 71 surveyed physicians who provided responses on how they address the management of patients who maintained either a pacemaker or a defibrillator during radiation treatment. Second, a case review study is presented involving 112 medical records reviewed at 18 institutions to determine whether there was a change in the radiation prescription for the treatment of the target cancer, the method of radiation delivery, or the method of radiation image acquisition. Statistics are provided to illustrate the level of administrative policy; the level of communication between radiation oncologists and heart specialists; American Joint Committee on Cancer (AJCC) staging and classification; National Comprehensive Cancer Network (NCCN) guidelines; tumor site; patient's sex; patient's age; device type; manufacturer; live monitoring; and the reported decisions for planning, delivery, and imaging. This survey revealed that 37% of patient treatments were considered for some sort of change in this regard, whereas 59% of patients were treated without regard to these alternatives when available. Only 3% of all patients were identified with an observable change in the functionality of the device or patient status in comparison with 96% of patients with normal behavior and operating devices. Documented changes in the patient's medical record included 1 device exhibiting failure at 0.3-Gy dose, 1 device exhibiting increased sensor rate during dose delivery, 1 patient having an irregular heartbeat leading to device reprogramming, and 1 patient complained of twinging in the chest wall that resulted in a respiratory arrest. Although policies and procedures should directly involve the qualified medical physicist for technical supervision, their sufficient involvement was typically not requested by most respondents. No treatment options were denied to any patient based on AJCC staging, classification, or NCCN practice standards.

  2. Internet Treatment Delivery of Parent-Adolescent Conflict Training for Families with an ADHD Teen: A Feasibility Study

    ERIC Educational Resources Information Center

    Carpenter, Erika M.; Frankel, Fred; Marina, Michael; Duan, Naihua; Smalley, Susan L.

    2004-01-01

    The present study examines the feasibility of Internet delivery of a Parent-Adolescent Conflict Training (PACT) program to families with an ADHD teen. The goals of the project are to ascertain the willingness of families to participate in this web-based study, identify relevant issues related to confidentiality of Internet data collection, and…

  3. Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma.

    PubMed

    Hall, Justin; Prabhakar, Shilpa; Balaj, Leonora; Lai, Charles P; Cerione, Richard A; Breakefield, Xandra O

    2016-04-01

    Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson's disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood-brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases. PMID:27017608

  4. Delivery validation of an automated modulated electron radiotherapy plan

    SciTech Connect

    Connell, T. Papaconstadopoulos, P.; Alexander, A.; Serban, M.; Devic, S.; Seuntjens, J.

    2014-06-15

    Purpose: Modulated electron radiation therapy (MERT) represents an active area of interest that offers the potential to improve healthy tissue sparing in treatment of certain cancer cases. Challenges remain however in accurate beamlet dose calculation, plan optimization, collimation method, and delivery accuracy. In this work, the authors investigate the accuracy and efficiency of an end-to-end MERT plan and automated delivery method. Methods: Treatment planning was initiated on a previously treated whole breast irradiation case including an electron boost. All dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. Results: The automated delivery, which covered four electron energies, 196 subfields, and 6183 total MU was completed in 25.8 min, including 6.2 min of beam-on time. The remainder of the delivery time was spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. Comparison of the planned and delivered film dose gave 3%/3mm gamma pass rates of 62.1%, 99.8%, 97.8%, 98.3%, and 98.7% for the 9, 12, 16, and 20 MeV, and combined energy deliveries, respectively. Delivery was also performed with a MapCHECK device and resulted in 3%/3  mm gamma pass rates of 88.8%, 86.1%, 89.4%, and 94.8% for the 9, 12, 16, and 20 MeV energies, respectively. Conclusions: Results of the authors’ study showed that an accurate delivery utilizing an add-on tertiary electron collimator is possible using Monte Carlo calculated plans and inverse optimization, which brings MERT closer to becoming a viable option for physicians in treating superficial malignancies.

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

    PubMed Central

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

    2011-01-01

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

  6. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. PMID:25703045

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

    PubMed Central

    2013-01-01

    Introduction Nanoscale gold particles (AuNPs) have wide perspectives for biomedical applications because of their unique biological properties, as antioxidative activity and potentials for drug delivery. Aims and objectives The aim was to test effects of AuNPs using suggested heart failure rat model to compare with proved medication Simdax, to test gold nanoparticle for drug delivery, and to test sonoporation effect to increase nanoparticles delivery into myocardial cells. Material and methods We performed biosafety and biocompatibility tests for AuNPs and conjugate with Simdax. For in vivo tests, we included Wistar rats weighing 180200 g (n = 54), received doxorubicin in cumulative dose of 12.0 mg/kg to model advance heart failure, registered by ultrasonography. We formed six groups: the first three groups of animals received, respectively, 0.06 ml Simdax, AuNPs, and conjugate (AuNPs-Simdax), intrapleurally, and the second three received them intravenously. The seventh group was control (saline). We performed dynamic assessment of heart failure regression in vivo measuring hydrothorax. Sonoporation of gold nanoparticles to cardiomyocytes was tested. Results We designed and constructed colloidal, spherical gold nanoparticles, AuNPs-Simdax conjugate, both founded biosafety (in cytotoxicity, genotoxicity, and immunoreactivity). In all animals of the six groups after the third day post-medication injection, no ascites and liver enlargement were registered (P < 0.001 vs controls). Conjugate injection showed significantly higher hydrothorax reduction than Simdax injection only (P < 0.01); gold nanoparticle injection showed significantly higher results than Simdax injection (P < 0.05). AuNPs and conjugate showed no significant difference for rat recovery. Difference in rat life continuity was significant between Simdax vs AuNPs (P < 0.05) and Simdax vs conjugate (P < 0.05). Sonoporation enhances AuNP transfer into the cell and mitochondria that were highly localized, superior to controls (P < 0.01 for both). Conclusions Gold nanoparticles of 30 nm and its AuNPs-Simdax conjugate gave positive results in biosafety and biocompatibility in vitro and in vivo. AuNPs-Simdax and AuNPs have similar significant cardioprotective effects in rats with doxorubicin-induced heart failure, higher than that of Simdax. Intrapleural (local) delivery is preferred over intravenous (systemic) delivery according to all tested parameters. Sonoporation is able to enhance gold nanoparticle delivery to myocardial cells in vivo. PMID:23889805

  8. MO-A-BRD-10: A Fast and Accurate GPU-Based Proton Transport Monte Carlo Simulation for Validating Proton Therapy Treatment Plans

    SciTech Connect

    Wan Chan Tseung, H; Ma, J; Beltran, C

    2014-06-15

    Purpose: To build a GPU-based Monte Carlo (MC) simulation of proton transport with detailed modeling of elastic and non-elastic (NE) protonnucleus interactions, for use in a very fast and cost-effective proton therapy treatment plan verification system. Methods: Using the CUDA framework, we implemented kernels for the following tasks: (1) Simulation of beam spots from our possible scanning nozzle configurations, (2) Proton propagation through CT geometry, taking into account nuclear elastic and multiple scattering, as well as energy straggling, (3) Bertini-style modeling of the intranuclear cascade stage of NE interactions, and (4) Simulation of nuclear evaporation. To validate our MC, we performed: (1) Secondary particle yield calculations in NE collisions with therapeutically-relevant nuclei, (2) Pencil-beam dose calculations in homogeneous phantoms, (3) A large number of treatment plan dose recalculations, and compared with Geant4.9.6p2/TOPAS. A workflow was devised for calculating plans from a commercially available treatment planning system, with scripts for reading DICOM files and generating inputs for our MC. Results: Yields, energy and angular distributions of secondaries from NE collisions on various nuclei are in good agreement with the Geant4.9.6p2 Bertini and Binary cascade models. The 3D-gamma pass rate at 2%–2mm for 70–230 MeV pencil-beam dose distributions in water, soft tissue, bone and Ti phantoms is 100%. The pass rate at 2%–2mm for treatment plan calculations is typically above 98%. The net computational time on a NVIDIA GTX680 card, including all CPU-GPU data transfers, is around 20s for 1×10{sup 7} proton histories. Conclusion: Our GPU-based proton transport MC is the first of its kind to include a detailed nuclear model to handle NE interactions on any nucleus. Dosimetric calculations demonstrate very good agreement with Geant4.9.6p2/TOPAS. Our MC is being integrated into a framework to perform fast routine clinical QA of pencil-beam treatment plans. Hardware for such a system will cost under $5000. This work was funded in part by a grant from Varian Medical Systems, Inc.

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

    PubMed

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

    2014-12-01

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

  10. Commissioning of an Integrated Platform for Time-Resolved Treatment Delivery in Scanned Ion Beam Therapy by Means of Optical Motion Monitoring

    PubMed Central

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

    2014-01-01

    The integrated use of optical technologies for patient monitoring is addressed in the framework of time-resolved treatment delivery for scanned ion beam therapy. A software application has been designed to provide the therapy control system (TCS) with a continuous geometrical feedback by processing the external surrogates tridimensional data, detected in real-time via optical tracking. Conventional procedures for phase-based respiratory phase detection were implemented, as well as the interface to patient specific correlation models, in order to estimate internal tumor motion from surface markers. In this paper, particular attention is dedicated to the quantification of time delays resulting from system integration and its compensation by means of polynomial interpolation in the time domain. Dedicated tests to assess the separate delay contributions due to optical signal processing, digital data transfer to the TCS and passive beam energy modulation actuation have been performed. We report the system technological commissioning activities reporting dose distribution errors in a phantom study, where the treatment of a lung lesion was simulated, with both lateral and range beam position compensation. The zero-delay systems integration with a specific active scanning delivery machine was achieved by tuning the amount of time prediction applied to lateral (14.61 ± 0.98 ms) and depth (34.1 ± 6.29 ms) beam position correction signals, featuring sub-millimeter accuracy in forward estimation. Direct optical target observation and motion phase (MPh) based tumor motion discretization strategies were tested, resulting in −0.3(2.3)% and −1.2(9.3)% median (IQR) percentual relative dose difference with respect to static irradiation, respectively. Results confirm the technical feasibility of the implemented strategy towards 4D treatment delivery, with negligible percentual dose deviations with respect to static irradiation. PMID:24354750

  11. Stomach specific polymeric low density microballoons as a vector for extended delivery of rabeprazole and amoxicillin for treatment of peptic ulcer.

    PubMed

    Choudhary, Sandeep; Jain, Ashay; Amin, Mohd Cairul Iqbal Mohd; Mishra, Vijay; Agrawal, Govind P; Kesharwani, Prashant

    2016-05-01

    The study was intended to develop a new intra-gastric floating in situ microballoons system for controlled delivery of rabeprazole sodium and amoxicillin trihydrate for the treatment of peptic ulcer disease. Eudragit S-100 and hydroxypropyl methyl cellulose based low density microballoons systems were fabricated by employing varying concentrations of Eudragit S-100 and hydroxypropyl methyl cellulose, to which varying concentrations of drug was added, and formulated by stirring at various speed and time to optimize the process and formulation variable. The formulation variables like concentration and ratio of polymers significantly affected the in vitro drug release from the prepared floating device. The validation of the gastro-retentive potential of the prepared microballoons was carried out in rabbits by orally administration of microballoons formulation containing radio opaque material. The developed formulations showed improved buoyancy and lower ulcer index as compared to that seen with plain drugs. Ulcer protective efficacies were confirmed in ulcer-bearing mouse model. In conclusion, greater compatibility, higher gastro-retention and higher anti-ulcer activity of the presently fabricated formulations to improve potential of formulation for redefining ulcer treatment are presented here. These learning exposed a targeted and sustained drug delivery potential of prepared microballoons in gastric region for ulcer therapeutic intervention as corroborated by in vitro and in vivo findings and, thus, deserves further attention for improved ulcer treatment. PMID:26859118

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

    PubMed

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

    2012-01-01

    Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the αvβ3 and αvβ5 integrins. Preclinical studies demonstrate antiangiogenic activity and anti-invasive activity in a number of glioma models. This study was designed to evaluate the efficacy and tumor delivery of cilengitide in patients with recurrent glioblastoma. Patients with recurrent glioblastoma who require a surgical resection for optimal clinical care received 3 intravenous doses of cilengitide at either 500 or 2000 mg (day -8, -4, -1) prior to undergoing tumor resection with corresponding blood samples for plasma to tumor comparisons. After recovery from surgery, patients were treated with cilengitide (2000 mg i.v. twice weekly, maximum of 2 years of treatment). The study accrued 30 patients with recurrent glioblastoma, 26 were evaluable for efficacy. The 6-month progression free survival rate was 12%. Cilengitide was detected in all tumor specimens with higher levels in the group receiving 2000 mg dosing while corresponding plasma concentrations were low, often below the lower limit of detection. These results confirm drug delivery and possibly retention in tumor. This study provides evidence that with established dosing, cilengitide is adequately delivered to the tumor, although as a single agent, efficacy in recurrent glioblastoma is modest. However, these results demonstrating drug delivery to tumor do support continued investigation of this agent as preliminary results from recent studies combining cilengitide with cytotoxic therapies are promising. PMID:21739168

  13. Cilengitide in Patients with Recurrent Glioblastoma: The Results of NABTC 03-02, a Phase II Trial with Measures of Treatment Delivery

    PubMed Central

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

    2015-01-01

    Purpose Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the αvβ3 and αvβ5 integrins. Preclinical studies demonstrate antiangiogenic activity and anti-invasive activity in a number of glioma models. This study was designed to evaluate the efficacy and tumor delivery of cilengitide in patients with recurrent glioblastoma. Experiment design Patients with recurrent glioblastoma who require a surgical resection for optimal clinical care received 3 intravenous doses of cilengitide at either 500 or 2000 mg (day -8, -4, -1) prior to undergoing tumor resection with corresponding blood samples for plasma to tumor comparisons. After recovery from surgery, patients were treated with cilengitide (2000 mg i.v. twice weekly, maximum of 2 years of treatment). Results The study accrued 30 patients with recurrent glioblastoma, 26 were evaluable for efficacy. The 6-month progression free survival rate was 12%. Cilengitide was detected in all tumor specimens with higher levels in the group receiving 2000 mg dosing while corresponding plasma concentrations were low, often below the lower limit of detection. These results confirm drug delivery and possibly retention in tumor. Conclusions This study provides evidence that with established dosing, cilengitide is adequately delivered to the tumor, although as a single agent, efficacy in recurrent glioblastoma is modest. However, these results demonstrating drug delivery to tumor do support continued investigation of this agent as preliminary results from recent studies combining cilengitide with cytotoxic therapies are promising. PMID:21739168

  14. Delivery presentations

    MedlinePlus

    Delivery presentation describes the way the baby is positioned to come down the birth canal for delivery. Your baby ... ultrasound may be able to confirm a brow presentation. More likely, your provider will detect this position ...

  15. Mesoporous Silica Nanoparticles with pH-Sensitive Nanovalves for Delivery of Moxifloxacin Provide Improved Treatment of Lethal Pneumonic Tularemia.

    PubMed

    Li, Zilu; Clemens, Daniel L; Lee, Bai-Yu; Dillon, Barbara Jane; Horwitz, Marcus A; Zink, Jeffrey I

    2015-11-24

    We have optimized mesoporous silica nanoparticles (MSNs) functionalized with pH-sensitive nanovalves for the delivery of the broad spectrum fluoroquinolone moxifloxacin (MXF) and demonstrated its efficacy in treating Francisella tularensis infections both in vitro and in vivo. We compared two different nanovalve systems, positive and negative charge modifications of the mesopores, and different loading conditions-varying pH, cargo concentration, and duration of loading-and identified conditions that maximize both the uptake and release capacity of MXF by MSNs. We have demonstrated in macrophage cell culture that the MSN-MXF delivery platform is highly effective in killing F. tularensis in infected macrophages, and in a mouse model of lethal pneumonic tularemia, we have shown that the drug-loaded MSNs are much more effective in killing F. tularensis than an equivalent amount of free MXF. PMID:26435204

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

    NASA Astrophysics Data System (ADS)

    Dhulekar, Jhilmil

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

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

    PubMed Central

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

    2014-01-01

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

  18. Microencapsulation: A promising technique for controlled drug delivery

    PubMed Central

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

    2010-01-01

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

  19. Preclinical Studies on Intestinal Administration of Antisense Oligonucleotides as a Model for Oral Delivery for Treatment of Duchenne Muscular Dystrophy

    PubMed Central

    van Putten, Maaike; Young, Courtney; van den Berg, Sjoerd; Pronk, Amanda; Hulsker, Margriet; Karnaoukh, Tatyana G; Vermue, Rick; van Dijk, Ko Willems; de Kimpe, Sjef; Aartsma-Rus, Annemieke

    2014-01-01

    Antisense oligonucleotides (AONs) used to reframe dystrophin mRNA transcripts for Duchenne muscular dystrophy (DMD) patients are tested in clinical trials. Here, AONs are administered subcutaneously and intravenously, while the less invasive oral route would be preferred. Oral delivery of encapsulated AONs supplemented with a permeation enhancer, sodium caprate, has been successfully used to target tumor necrosis factor (TNF)-α expression in liver. To test the feasibility of orally delivered AONs for DMD, we applied 2′-O-methyl phosphorothioate AONs (with or without sodium caprate supplementation) directly to the intestine of mdx mice and compared pharmacokinetics and -dynamics with intravenous, intraperitoneal, and subcutaneous delivery. Intestinally infused AONs were taken up, but resulted in lower plasma levels compared to other delivery routes, although bioavailability could be largely improved by supplementation of sodium caprate. After intestinal infusion, AON levels in all tissues were lower than for other administration routes, as were the ratios of target versus nontarget organ levels, except for diaphragm and heart where comparable levels and ratios were observed. For each administration route, low levels of exon skipping in triceps was observed 3 hours post-AON administration. These data suggest that oral administration of naked 2′-O-methyl phosphorothioate AONs may be feasible, but only when high AON concentrations are used in combination with sodium caprate. PMID:25405468

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

    SciTech Connect

    Desai, V; Fagerstrom, J; Bayliss, A; Kissick, M

    2014-06-01

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

  1. Is scoring system of computed tomography based metric parameters can accurately predicts shock wave lithotripsy stone-free rates and aid in the development of treatment strategies?

    PubMed Central

    Badran, Yasser Ali; Abdelaziz, Alsayed Saad; Shehab, Mohamed Ahmed; Mohamed, Hazem Abdelsabour Dief; Emara, Absel-Aziz Ali; Elnabtity, Ali Mohamed Ali; Ghanem, Maged Mohammed; ELHelaly, Hesham Abdel Azim

    2016-01-01

    Objective: The objective was to determine the predicting success of shock wave lithotripsy (SWL) using a combination of computed tomography based metric parameters to improve the treatment plan. Patients and Methods: Consecutive 180 patients with symptomatic upper urinary tract calculi 20 mm or less were enrolled in our study underwent extracorporeal SWL were divided into two main groups, according to the stone size, Group A (92 patients with stone ≤10 mm) and Group B (88 patients with stone >10 mm). Both groups were evaluated, according to the skin to stone distance (SSD) and Hounsfield units (≤500, 500–1000 and >1000 HU). Results: Both groups were comparable in baseline data and stone characteristics. About 92.3% of Group A rendered stone-free, whereas 77.2% were stone-free in Group B (P = 0.001). Furthermore, in both group SWL success rates was a significantly higher for stones with lower attenuation <830 HU than with stones >830 HU (P < 0.034). SSD were statistically differences in SWL outcome (P < 0.02). Simultaneous consideration of three parameters stone size, stone attenuation value, and SSD; we found that stone-free rate (SFR) was 100% for stone attenuation value <830 HU for stone <10 mm or >10 mm but total number SWL sessions and shock waves required for the larger stone group were higher than in the smaller group (P < 0.01). Furthermore, SFR was 83.3% and 37.5% for stone <10 mm, mean HU >830, SSD 90 mm and SSD >120 mm, respectively. On the other hand, SFR was 52.6% and 28.57% for stone >10 mm, mean HU >830, SSD <90 mm and SSD >120 mm, respectively. Conclusion: Stone size, stone density (HU), and SSD is simple to calculate and can be reported by radiologists to applying combined score help to augment predictive power of SWL, reduce cost, and improving of treatment strategies. PMID:27141192

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

    PubMed

    Abdin, Amany A

    2013-10-15

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

  3. A GLP-Compliant Toxicology and Biodistribution Study: Systemic Delivery of an rAAV9 Vector for the Treatment of Mucopolysaccharidosis IIIB.

    PubMed

    Meadows, Aaron S; Duncan, F Jason; Camboni, Marybeth; Waligura, Kathryn; Montgomery, Chrystal; Zaraspe, Kimberly; Naughton, Bartholomew J; Bremer, William G; Shilling, Christopher; Walker, Christopher M; Bolon, Brad; Flanigan, Kevin M; McBride, Kim L; McCarty, Douglas M; Fu, Haiyan

    2015-12-01

    No treatment is currently available for mucopolysaccharidosis (MPS) IIIB, a neuropathic lysosomal storage disease due to defect in α-N-acetylglucosaminidase (NAGLU). In preparation for a clinical trial, we performed an IND-enabling GLP-toxicology study to assess systemic rAAV9-CMV-hNAGLU gene delivery in WT C57BL/6 mice at 1 × 10(14) vg/kg and 2 × 10(14) vg/kg (n = 30/group, M:F = 1:1), and non-GLP testing in MPS IIIB mice at 2 × 10(14) vg/kg. Importantly, no adverse clinical signs or chronic toxicity were observed through the 6 month study duration. The rAAV9-mediated rNAGLU expression was rapid and persistent in virtually all tested CNS and somatic tissues. However, acute liver toxicity occurred in 33% (5/15) WT males in the 2 × 10(14) vg/kg cohort, which was dose-dependent, sex-associated, and genotype-specific, likely due to hepatic rNAGLU overexpression. Interestingly, a significant dose response was observed only in the brain and spinal cord, whereas in the liver at 24 weeks postinfection (pi), NAGLU activity was reduced to endogenous levels in the high dose cohort but remained at supranormal levels in the low dose group. The possibility of rAAV9 germline transmission appears to be minimal. The vector delivery resulted in transient T-cell responses and characteristic acute antibody responses to both AAV9 and rNAGLU in all rAAV9-treated animals, with no detectable impacts on tissue transgene expression. This study demonstrates a generally safe and effective profile, and may have identified the upper dosing limit of rAAV9-CMV-hNAGLU via systemic delivery for the treatment of MPS IIIB. PMID:26684447

  4. SU-C-17A-07: The Development of An MR Accelerator-Enabled Planning-To-Delivery Technique for Stereotactic Palliative Radiotherapy Treatment of Spinal Metastases

    SciTech Connect

    Hoogcarspel, S J; Kontaxis, C; Velden, J M van der; Bol, G H; Vulpen, M van; Lagendijk, J J W; Raaymakers, B W

    2014-06-01

    Purpose: To develop an MR accelerator-enabled online planning-todelivery technique for stereotactic palliative radiotherapy treatment of spinal metastases. The technical challenges include; automated stereotactic treatment planning, online MR-based dose calculation and MR guidance during treatment. Methods: Using the CT data of 20 patients previously treated at our institution, a class solution for automated treatment planning for spinal bone metastases was created. For accurate dose simulation right before treatment, we fused geometrically correct online MR data with pretreatment CT data of the target volume (TV). For target tracking during treatment, a dynamic T2-weighted TSE MR sequence was developed. An in house developed GPU based IMRT optimization and dose calculation algorithm was used for fast treatment planning and simulation. An automatically generated treatment plan developed with this treatment planning system was irradiated on a clinical 6 MV linear accelerator and evaluated using a Delta4 dosimeter. Results: The automated treatment planning method yielded clinically viable plans for all patients. The MR-CT fusion based dose calculation accuracy was within 2% as compared to calculations performed with original CT data. The dynamic T2-weighted TSE MR Sequence was able to provide an update of the anatomical location of the TV every 10 seconds. Dose calculation and optimization of the automatically generated treatment plans using only one GPU took on average 8 minutes. The Delta4 measurement of the irradiated plan agreed with the dose calculation with a 3%/3mm gamma pass rate of 86.4%. Conclusions: The development of an MR accelerator-enabled planning-todelivery technique for stereotactic palliative radiotherapy treatment of spinal metastases was presented. Future work will involve developing an intrafraction motion adaptation strategy, MR-only dose calculation, radiotherapy quality-assurance in a magnetic field, and streamlining the entire treatment process on an MR accelerator.

  5. The spacer arm length in cell-penetrating peptides influences chitosan/siRNA nanoparticle delivery for pulmonary inflammation treatment

    NASA Astrophysics Data System (ADS)

    Jeong, Eun Ju; Choi, Moonhwan; Lee, Jangwook; Rhim, Taiyoun; Lee, Kuen Yong

    2015-11-01

    Although chitosan and its derivatives have been frequently utilized as delivery vehicles for small interfering RNA (siRNA), it is challenging to improve the gene silencing efficiency of chitosan-based nanoparticles. In this study, we hypothesized that controlling the spacer arm length between a cell-penetrating peptide (CPP) and a nanoparticle could be critical to enhancing the cellular uptake as well as the gene silencing efficiency of conventional chitosan/siRNA nanoparticles. A peptide consisting of nine arginine units (R9) was used as a CPP, and the spacer arm length was controlled by varying the number of glycine units between the peptide (R9Gn) and the nanoparticle (n = 0, 4, and 10). Various physicochemical characteristics of R9Gn-chitosan/siRNA nanoparticles were investigated in vitro. Increasing the spacing arm length did not significantly affect the complex formation between R9Gn-chitosan and siRNA. However, R9G10-chitosan was much more effective in delivering genes both in vitro and in vivo compared with non-modified chitosan (without the peptide) and R9-chitosan (without the spacer arm). Chitosan derivatives modified with oligoarginine containing a spacer arm can be considered as potential delivery vehicles for various genes.Although chitosan and its derivatives have been frequently utilized as delivery vehicles for small interfering RNA (siRNA), it is challenging to improve the gene silencing efficiency of chitosan-based nanoparticles. In this study, we hypothesized that controlling the spacer arm length between a cell-penetrating peptide (CPP) and a nanoparticle could be critical to enhancing the cellular uptake as well as the gene silencing efficiency of conventional chitosan/siRNA nanoparticles. A peptide consisting of nine arginine units (R9) was used as a CPP, and the spacer arm length was controlled by varying the number of glycine units between the peptide (R9Gn) and the nanoparticle (n = 0, 4, and 10). Various physicochemical characteristics of R9Gn-chitosan/siRNA nanoparticles were investigated in vitro. Increasing the spacing arm length did not significantly affect the complex formation between R9Gn-chitosan and siRNA. However, R9G10-chitosan was much more effective in delivering genes both in vitro and in vivo compared with non-modified chitosan (without the peptide) and R9-chitosan (without the spacer arm). Chitosan derivatives modified with oligoarginine containing a spacer arm can be considered as potential delivery vehicles for various genes. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06903c

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

    PubMed

    Korkmaz, Levent; Acar, Zeydin; Dursun, Ihsan; Akyüz, Ali Rıza; Korkmaz, Ayca Ata

    2014-03-01

    In this case report, we present the occlusion of multiple coronary artery fistulae originating from proximal left anterior descending (LAD) and right sinus valsavla and empting to the pulmonary artery at the same place. We occluded LAD fistulae by using thrombus aspiration catheter as a delivery guide. To the best of our knowlege, this is the first case of occlusion of coronary fistulae with the help of thrombus aspiration catheter. Our experience may suggest that thrombus aspiration catheters can be used in treating coronary artery fistulae with difficult anotomy. PMID:24748888

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

    PubMed Central

    Korkmaz, Levent; Acar, Zeydin; Dursun, İhsan; Akyüz, Ali Rıza; Korkmaz, Ayca Ata

    2014-01-01

    In this case report, we present the occlusion of multiple coronary artery fistulae originating from proximal left anterior descending (LAD) and right sinus valsavla and empting to the pulmonary artery at the same place. We occluded LAD fistulae by using thrombus aspiration catheter as a delivery guide. To the best of our knowlege, this is the first case of occlusion of coronary fistulae with the help of thrombus aspiration catheter. Our experience may suggest that thrombus aspiration catheters can be used in treating coronary artery fistulae with difficult anotomy. PMID:24748888

  8. Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide/protein in the treatment of ocular diseases.

    PubMed

    Patel, Sulabh P; Vaishya, Ravi; Patel, Ashaben; Agrahari, Vibhuti; Pal, Dhananjay; Mitra, Ashim K

    2016-03-01

    This manuscript is focussed on the development of pentablock (PB) copolymer based sustained release formulation for the treatment of posterior segment ocular diseases. We have successfully synthesised biodegradable and biocompatible PB copolymers for the preparation of nanoparticles (NPs) and thermosensitive gel. Achieving high drug loading with hydrophilic biotherapeutics (peptides/proteins) is a challenging task. Moreover, small intravitreal injection volume (≤100 μL) requires high loading to develop a long term (six months) sustained release formulation. We have successfully investigated various formulation parameters to achieve maximum peptide/protein (octreotide, insulin, lysozyme, IgG-Fab, IgG, and catalase) loading in PB NPs. Improvement in drug loading can facilitate delivery of larger doses of therapeutic proteins via limited injection volume. A composite formulation comprised of NPs in gel system exhibited sustained release (without burst effect) of peptides and proteins, may serve as a platform technology for the treatment of posterior segment ocular diseases. PMID:26964498

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

    PubMed

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

    2014-01-01

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

  10. Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya

    PubMed Central

    Brooker, Simon J; Mwandawiro, Charles S; Halliday, Katherine E; Njenga, Sammy M; Mcharo, Carlos; Gichuki, Paul M; Wasunna, Beatrice; Kihara, Jimmy H; Njomo, Doris; Alusala, Dorcas; Chiguzo, Athuman; Turner, Hugo C; Teti, Caroline; Gwayi-Chore, Claire; Nikolay, Birgit; Truscott, James E; Hollingsworth, T Déirdre; Balabanova, Dina; Griffiths, Ulla K; Freeman, Matthew C; Allen, Elizabeth; Pullan, Rachel L; Anderson, Roy M

    2015-01-01

    Introduction In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal? Methods and analysis Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision—termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. Ethics and dissemination Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a dedicated web site. Trial registration number NCT02397772. PMID:26482774

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

    PubMed Central

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

    2012-01-01

    The overall objective of liposomal drug delivery is to selectively target drug delivery to diseased tissue, while minimizing drug delivery to critical normal tissues. The purpose of this review is to provide an overview of temperature-sensitive liposomes in general and the Low Temperature-Sensitive Liposome (LTSL) in particular. We give a brief description of the material design of LTSL and highlight the likely mechanism behind temperature-triggered drug release. A complete review of the progress and results of the latest preclinical and clinical studies that demonstrate enhanced drug delivery with the combined treatment of hyperthermia and liposomes is provided as well as a clinical perspective on cancers that would benefit from hyperthermia as an adjuvant treatment for temperature-triggered chemotherapeutics. This review discusses the ideas, goals, and processes behind temperature-sensitive liposome development in the laboratory to the current use in preclinical and clinical settings. PMID:23807899

  12. Development and evaluation of aerosol delivery of antivirals for the treatment of equine virus induced respiratory infections

    SciTech Connect

    Martens, J.G.

    1985-01-01

    An aerosol delivery system incorporating the DeVilbiss ultrasonic nebulizer was developed for antiviral chemotherapy of equine viral respiratory infections. The system's delivery capabilities were proven effective by two modes of analysis: (a) a non-destructive, non-invasive radioactive tracer method utilizing a saline solution of DTPA labelled 99mTc and, (b) an invasive-terminal study using fluorescent polystyrene monodispersed latex particles. Particles were efficiently distributed throughout the lung parenchyma with deposition more heavily concentrated in the tracheobronchial region. Amantadine HCl was administered to the lungs of a yearling horse and three yearling Shetland ponies over a single 15-30 minute period with no untoward side effects. Likewise, ribavirin was aerosolized into the respiratory trace of an adult pony and a yearling horse for 15-30 minutes twice a day for three and seven days respectively. Neither the horse nor pony demonstrated signs of clinical illness or other signs of ribavirin toxicity. Attempts to produce a reproducible equine influenza disease model were made. During these studies, the authors were unsuccessful in developing a consistent respiratory disease model. Without this model the efficacy of antiviral compounds cannot be assessed. From the data generated in these studies, the implication of equine influenza viruses as the major single etiological agents responsible for equine respiratory disease is brought into question. Further, the author proposed that equine respiratory disease is a multiple agent-induced disease, which needs extensive investigation.

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Grading More Accurately

    ERIC Educational Resources Information Center

    Rom, Mark Carl

    2011-01-01

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

  16. Unit costs for delivery of antiretroviral treatment and prevention of mother-to-child transmission of HIV: a systematic review for low- and middle-income countries.

    PubMed

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

    2011-07-01

    As antiretroviral treatment (ART) for HIV/AIDS is scaled up globally, information on per-person costs is critical to improve efficiency in service delivery and to maximize coverage and health impact. The objective of this study was to review studies on unit costs for delivery of adult and paediatric ART per patient-year, and prevention of mother-to-child transmission (PMTCT) interventions per mother-infant pair screened or treated, in low- and middle-income countries. A systematic review was conducted of English, French and Spanish publications from 2001 to 2009, reporting empirical costing that accounted for at least antiretroviral (ARV) medicines, laboratory testing and personnel. Expenditures were analysed by country-income level and cost component. All costs were standardized to $US, year 2009 values. Several sensitivity analyses were conducted. Analyses covered 29 eligible, comprehensive, costing studies. In the base case, in low-income countries (LIC), median ART cost per patient-year was $US792 (mean: 839, range: 682-1089); for lower-middle-income countries (LMIC), the median was $US932 (mean: 1246, range: 156-3904); and, for upper-middle-income countries (UMIC), the median was $US1454 (mean: 2783, range: 1230-5667). ARV drugs were the largest component of overall ART costs in all settings (64%, 50% and 47% in LIC, LMIC and UMIC, respectively). Of 26 ART studies, 14 reported the drug regimes used, and only one study explicitly reported second-line treatment costs. The second cost driver was laboratory cost in LIC and LMIC (14% and 20%), and personnel costs in UMIC (26%). Two ART studies specified the types of laboratory tests costed, and three studies specifically included above facility-level personnel costs. Three studies reported detailed PMTCT costs, and three studies reported on paediatric ART. There is a paucity of data on the full unit costs for delivery of ART and PMTCT, particularly for LIC and middle-income countries. Heterogeneity in activities costed, and insufficient detail regarding components included in the costing, hampers standardization of unit cost measures. Evaluation of programme-level unit costs would benefit from international guidance on standardized costing methods, and expenditure categories and definitions. Future work should help elucidate the sources of the large variations in delivery unit costs across settings with similar income and epidemiological characteristics. PMID:21671687

  17. Community-directed delivery of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis in Cameroon

    PubMed Central

    Wanji, Samuel; Tendongfor, Nicholas; Nji, Theolbald; Esum, Mathias; Che, Julious N; Nkwescheu, Armand; Alassa, Fifen; Kamnang, Geremy; Enyong, Peter A; Taylor, Mark J; Hoerauf, Achim; Taylor, David W

    2009-01-01

    Background Severe side effects following ivermectin treatment of onchocerciasis in areas of co-endemicity with loaisis have been an impediment for the work of the African Programme for Onchocerciasis Control (APOC) in forested regions of several countries. Doxycycline has been shown to be effective in the treatment of onchocerciasis and has the added advantages of killing adult Onchocerca volvulus but neither adult Loa loa nor their microfilariae. This drug therefore offers great potential for the treatment of onchocerciasis in areas of co-endemicity with loiasis. The limitation of use of this drug is the duration of treatment that may pose a potential problem with therapeutic coverage and compliance with treatment. To benefit from the advantages that doxycycline offers in the treatment of onchocerciasis, it will be necessary to establish an effective distribution system that can access remote communities. This study assessed the feasibility of a large-scale distribution of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis using a community-directed approach. Methods The study was carried out in 5 health areas co-endemic for Onchocerca volvulus and Loa loa which had no prior experience of the Community Directed Treatment with Ivermectin (CDTI). The community-directed delivery process was introduced using a cascade mechanism from the central health system that passed through the regional health delegation, health district and the health areas. Community health implementers (CHIs) were trained to deliver doxycycline to community members and, under the supervision of the health system, to monitor and document drug intake and side effects. Results The community members adhered massively to the process. Of the 21355 individuals counted, 17519 were eligible for treatment and 12936 were treated with doxycycline; giving a therapeutic coverage of eligible population of 73.8%. Of the 12936 who started the treatment, 97.5% complied by the end of six weeks. No serious side effect was registered during the six week treatment. Conclusion This study indicates that when empowered the community health implementers can successfully deliver doxycycline for six weeks for the treatment of onchocerciasis in areas of co-endemicity with loiasis. The therapeutic coverage and the compliance treatment rate achieved in this study coupled to the known efficacy of doxycycline on O. volvulus, are indicators that the strategy involving the mass administration of doxycycline can be used to control onchocerciasis in those areas of co-endemicity with loiasis where ivermectin may be contraindicated. PMID:19712455

  18. [Home delivery].

    PubMed

    Olivier, S; Guidicelli, B; Gamerre, M

    1994-10-01

    Home delivery, although unconventional, has not totally disappeared. It sometimes results from the desire to "demedicalise" an event deemed natural and is sometimes the consequence of government policy and hence approved by medical authorities. This is the unique situation of Holland, where a highly efficient home delivery system has been created, with the possibility of transfer of the mother at any time to rapidly available emergency medical teams. In fact the large majority of home deliveries are accidental, unprepared and take place in the absence of any medical or paramedical assistance. All available studies show that perinatal and maternal morbidity associated with these accidental deliveries is greater than that of hospital deliveries, and this despite the setting up of emergency services responding as soon as a distress call is received. Home delivery should remain the exception at present since it is unable to guarantee a birth as undangerous as possible. PMID:7817075

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

    PubMed

    Harris, M

    1994-01-01

    Sexual abuse trauma and chronic revictimization are central to the experience of many women diagnosed with severe mental illness. The high reported prevalence rates of sexual abuse trauma among these women necessitate that program planners and clinicians be prepared to adapt their treatment interventions for use with trauma survivors. This article describes how current treatment approaches for women diagnosed with severe mental illness can be adapted to accommodate the special needs and vulnerabilities of sexual abuse trauma survivors. A history of trauma added to the clinical picture of longstanding and severe mental illness poses new diagnostic and treatment considerations, which are discussed. The full range of rehabilitation services--case management, residential placement and supervision, inpatient hospitalization, medication management, network intervention, and social skills training--must be grounded in an understanding of the trauma experience, informed by accurate assessment of the trauma, and accommodated to the woman's specific history of sexual abuse trauma. PMID:10138013

  20. Tumor pHe-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment

    NASA Astrophysics Data System (ADS)

    Chen, Fengqian; Zhang, Jinming; Wang, Lu; Wang, Yitao; Chen, Meiwan

    2015-09-01

    The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 mM) in tumor tissue/cells, we firstly designed a novel d-α-tocopheryl polyethylene glycol 1000-poly(β-amino ester) block copolymer containing disulfide linkages (TPSS). TPSS nanoparticles (NPs) with pH- and redox-sensitive behaviors were developed for on-demand delivery of docetaxel (DTX) in hepatocellular carcinoma. DTX/TPSS NPs exhibited sensitive surface charge reversal from -47.6 +/- 2.5 mV to +22.5 +/- 3.2 mV when the pH decreased from 7.4 to 6.5, to simulate the pHe. Meanwhile, anabatic drug release of DTX/TPSS NPs was observed in PBS buffer (pH 6.5, 10 mM GSH). Due to the synergism between the pHe-triggered charge reversal and the redox-triggered drug release, enhanced drug uptake and anticancer efficacy were observed in HepG2 and SMMC 7721 cells treated with DTX/TPSS NPs. The positively charged NPs exhibited a stronger inhibitory effect on cell proliferation, promoted cell cycle arrest in the G2/M phase, and increased the rate of apoptosis. More importantly, based on the higher tumor accumulation of TPSS vehicles in vivo, a significant suppression of tumor growth, but without side-effects, was observed when DTX/TPSS NPs were injected intravenously into HepG2 xenograft tumor-bearing mice. Collectively, these results demonstrate that the newly developed dual-functional TPSS copolymer may be utilized as a drug delivery system for anticancer therapy.The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano-medicine therapy. Because of the slightly acidic extracellular environment (pHe ~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 mM) in tumor tissue/cells, we firstly designed a novel d-α-tocopheryl polyethylene glycol 1000-poly(β-amino ester) block copolymer containing disulfide linkages (TPSS). TPSS nanoparticles (NPs) with pH- and redox-sensitive behaviors were developed for on-demand delivery of docetaxel (DTX) in hepatocellular carcinoma. DTX/TPSS NPs exhibited sensitive surface charge reversal from -47.6 +/- 2.5 mV to +22.5 +/- 3.2 mV when the pH decreased from 7.4 to 6.5, to simulate the pHe. Meanwhile, anabatic drug release of DTX/TPSS NPs was observed in PBS buffer (pH 6.5, 10 mM GSH). Due to the synergism between the pHe-triggered charge reversal and the redox-triggered drug release, enhanced drug uptake and anticancer efficacy were observed in HepG2 and SMMC 7721 cells treated with DTX/TPSS NPs. The positively charged NPs exhibited a stronger inhibitory effect on cell proliferation, promoted cell cycle arrest in the G2/M phase, and increased the rate of apoptosis. More importantly, based on the higher tumor accumulation of TPSS vehicles in vivo, a significant suppression of tumor growth, but without side-effects, was observed when DTX/TPSS NPs were injected intravenously into HepG2 xenograft tumor-bearing mice. Collectively, these results demonstrate that the newly developed dual-functional TPSS copolymer may be utilized as a drug delivery system for anticancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04612b

  1. Transient gestational diabetes insipidus diagnosed in successive pregnancies: review of pathophysiology, diagnosis, treatment, and management of delivery.

    PubMed

    Kalelioglu, Ibrahim; Kubat Uzum, Ayse; Yildirim, Alkan; Ozkan, Tulay; Gungor, Funda; Has, Recep

    2007-01-01

    Gestational diabetes insipidus (GDI) is a rare disorder characterised by polyuria, polydypsia, and excessive thirst usually manifesting in the third trimester of pregnancy. The etiology is thought to depend on excessive vasopressinase activity, a placental enzyme that degrades arginine-vasopressin (AVP), but not 1-deamino-8-D: -arginine vasopressin (dDAVP), which is a synthetic form. This is a transient syndrome and may be associated with acute fatty liver of pregnancy and preeclampsia. The use of dDAVP in symptomatic cases has been proven as a safe method for both the mother and the fetus during the pregnancy. We report a case of recurrent gestational diabetes insipidus in successive pregnancies, which responded to dDAVP and subsided after delivery. PMID:17308961

  2. Successful pregnancy and delivery on prasugrel treatment: considerations for the use of dual antiplatelet therapy during pregnancy in clinical practice.

    PubMed

    Tello-Montoliu, Antonio; Seecheran, Naveen A; Angiolillo, Dominick J

    2013-10-01

    Ischemic heart disease is uncommon during pregnancy, occurring in approximately 1/10,000 pregnancies resulting in live births. However, the increased age and fertility of mothers has suggested that the coexistence of pregnancy and coronary artery disease is likely to increase. A subject of debate is the management of dual antiplatelet therapy among pregnant women. The potential teratogeneous effects, particularly with regards to thienopyridines, on the fetus are not fully established. In addition, the use of dual antiplatelet therapy is associated with an increased risk for bleeding events, raising concerns in the peripartum period with regards to the route of delivery and choice of anesthestic techniques. Limited data and experience is available with clopidogrel, the most commonly used thienopyridine. Prasugrel is third generation thienopyridine recently introduced into clinical practice with ever growing use in the setting of acute coronary syndrome patients undergoing percutaneous coronary interventions. The present manuscript describes the first case report of a pregnancy while on prasugrel therapy. PMID:23143651

  3. Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment.

    PubMed

    Posadowska, Urszula; Brzychczy-Wloch, Monika; Pamula, Elzbieta

    2016-01-01

    Infection spreading in the skeletal system leading to osteomyelitis can be prevented by the prolonged administration of antibiotics in high doses. However systemic antibiotherapy, besides its inconvenience and often low efficacy, provokes numerous side effects. Thus, we formulated a new injectable nanoparticle-loaded system for the local delivery of vancomycin (Vanc) applied in a minimally-invasive way. Vanc was encapsulated in poly(L-lactide-co-glycolide) nanoparticles (NPs) by double-emulsification. The size (258 ± 11 nm), polydispersity index (0.240 ± 0.003) and surface potential (-25.9 ± 0.2 mV) of NPs were determined by dynamic light scattering and capillary electrophoresis measurements. They have a spherical morphology and a smooth topography as observed using atomic force microscopy. Vanc loading and encapsulation efficiencies were 8.8 ± 0.1 and 55.2 ± 0.5 %, respectively, based on fluorescence spectroscopy assays. In order to ensure injectability, NPs were suspended in gellan gum and cross-linked with Ca(2+); also a portion of dissolved antibiotic was added to the system. The resulting system was found to be injectable (extrusion force 11.3 ± 1.1 N), reassembled its structure after breaking as shown by rheology tests and ensured required burst release followed by sustained Vanc delivery. The system was cytocompatible with osteoblast-like MG-63 cells (no significant impact on cells' viability was detected). Growth of Staphylococcus spp. reference strains and also those isolated from osteomyelitic joints was inhibited in contact with the injectable system. As a result we obtained a biocompatible system displaying ease of application (low extrusion force), self-healing ability after disruption, adjustable drug release and antimicrobial properties. PMID:26621310

  4. A Novel Treatment Method for Lymph Node Metastasis Using a Lymphatic Drug Delivery System with Nano/Microbubbles and Ultrasound

    PubMed Central

    Kato, Shigeki; Mori, Shiro; Kodama, Tetsuya

    2015-01-01

    Chemotherapy based on hematogenous administration of drugs to lymph nodes (LNs) located outside the surgically resected area shows limited tissue selectivity and inadequate response rates, resulting in poor prognosis. Here, we demonstrate proof of concept for a lymphatic drug delivery system using nano/microbubbles (NMBs) and ultrasound (US) to achieve sonoporation in LNs located outside the dissection area. First, we demonstrated the in vitro effectiveness of doxorubicin (Dox) delivered into three different tumor cell lines by sonoporation. Sonoporation increased the Dox autofluorescence signal and resulted in a subsequent decrease in cell viability. Next, we verified the antitumor effects of Dox in vivo using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs reaching 10 mm in diameter. We defined the subiliac LN (SiLN) as the upstream LN within the dissection area, and the proper axillary LN (PALN) as the downstream LN outside the dissection area. Dox and NMBs were injected into the SiLN and delivered to the PALN via lymphatic vessels; the PALN was then exposed to US when it had filled with solution. We found that sonoporation enhanced the intracellular uptake of Dox leading to high cytotoxicity. We also found that sonoporation induced extravasation of Dox from lymphatic endothelia and penetration of Dox into tumor tissues within the PALN. Furthermore, our method inhibited tumor growth and diminished blood vessels in the PALN while avoiding systemic toxic effects of Dox. Our findings indicate that a lymphatic drug delivery system with sonoporation represents a promising method for treating metastatic LNs located outside the dissection area. PMID:26640589

  5. Systematic measurements of whole-body dose distributions for various treatment machines and delivery techniques in radiation therapy

    SciTech Connect

    Haelg, Roger A.; Besserer, Juergen; Schneider, Uwe

    2012-12-15

    Purpose: Contemporary radiotherapy treatment techniques, such as intensity-modulated radiation therapy and volumetric modulated arc therapy, could increase the radiation-induced malignancies because of the increased beam-on time, i.e., number of monitor units needed to deliver the same dose to the target and the larger volume irradiated with low doses. In this study, whole-body dose distributions from typical radiotherapy patient plans using different treatment techniques and therapy machines were measured using the same measurement setup and irradiation intention. Methods: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The dose distributions from 6 MV beams were compared in terms of treatment technique (3D-conformal, intensity-modulated radiation therapy, volumetric modulated arc therapy, helical TomoTherapy, stereotactic radiotherapy, hard wedges, and flattening filter-free radiotherapy) and therapy machine (Elekta, Siemens and Varian linear accelerators, Accuray CyberKnife and TomoTherapy). Results: Close to the target, the doses from intensity-modulated treatments (including flattening filter-free) were below the dose from a static treatment plan, whereas the CyberKnife showed a larger dose by a factor of two. Far away from the treatment field, the dose from intensity-modulated treatments showed an increase in dose from stray radiation of about 50% compared to the 3D-conformal treatment. For the flattening filter-free photon beams, the dose from stray radiation far away from the target was slightly lower than the dose from a static treatment. The CyberKnife irradiation and the treatment using hard wedges increased the dose from stray radiation by nearly a factor of three compared to the 3D-conformal treatment. Conclusions: This study showed that the dose outside of the treated volume is influenced by several sources. Therefore, when comparing different treatment techniques, the dose ratios vary with distance to the isocenter. The effective dose outside the treated volume of intensity-modulated treatments with or without flattening filter was 10%-30% larger when compared to 3D-conformal radiotherapy. This dose increase is much lower than the monitor unit scaled effective dose from a static treatment.

  6. The application of electron beam delivery using dose rate variation and dynamic couch motion in conformal treatment of the cranial-spinal axis

    SciTech Connect

    Chapek, Julie; Watson, Gordon; Smith, Lynn M.; Leavitt, Dennis

    2002-12-31

    Radiation therapy to the cranial-spinal axis is typically targeted to the spinal cord and to the cerebrospinal fluid (CSF) in the subarachnoid space adjacent to the spinal cord and brain. Standard techniques employed in the treatment of the whole central nervous system do little to compensate for the varying depths of spinal cord along the length of the spinal field. Lateral simulation films, sagittal magnetic resonance imaging (MRI), or computerized tomography (CT) are used to estimate an average prescription depth for treatment along the spine field. However, due to the varying depth of the target along the spinal axis, even with the use of physical compensators, there can be considerable dose inhomogeneity along the spine field. With the advent of treatment machines that have full dynamic capabilities, a technique has been devised that will allow for more conformal dose distribution along the full length of the spinal field. This project simulates this technique utilizing computer-controlled couch motion to deliver multiple small electron beams of differing energies and intensities. CT planning determines target depth along the entire spine volume. The ability to conform dose along the complete length of the treatment field is investigated through the application of superpositioning of the fields as energies and intensities change. The positioning of each beam is registered with the treatment couch dynamic motion. This allows for 1 setup in the treatment room rather than multiple setups for each treatment position, which would have been previously required. Dose-volume histograms are utilized to evaluate the dose delivered to structures in the beam exit region. This technique will allow for precise localization and delivery of a homogeneous dose to the entire CSF space.

  7. Accurate monotone cubic interpolation

    NASA Technical Reports Server (NTRS)

    Huynh, Hung T.

    1991-01-01

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

  8. Accurate Finite Difference Algorithms

    NASA Technical Reports Server (NTRS)

    Goodrich, John W.

    1996-01-01

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

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

    PubMed

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

    2011-05-01

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

  10. A case study using a patient satisfaction survey to improve the delivery and effectiveness of drug addiction treatment services: marketing implications and organizational impact.

    PubMed

    Hogan, Beth; Hershey, Lewis; Ritchey, Steven

    2007-01-01

    Drug abuse and addiction continues to negatively impact many lives in this country. The United States health care system has grappled with how to best serve this vulnerable population. Since the personal and societal costs of addiction are high, all recent iterations of the United States strategic health plans (such as Healthy People 2010) have prioritized this area for improvement. At the local level, health care providers who care for those with addictions are challenged with shrinking insurance coverage for services, a difficult patient population, lack of treatment options, growing ranks of indigent patients, as well as a plethora of additional management challenges. It is known that successful treatment is integrally linked with patient satisfaction with services. The most critical factors in successful addiction treatment (from a patient's perspective) are (1) their belief that the counselor cares about them and, (2) their belief that they can recover. This paper reports a case study in the use of a patient satisfaction survey as a quality management/service refinement tool within a methadone treatment setting. Results indicate that the use of the survey itself provides patients with a tangible cue supporting the presence of the critical success factors. Further, the use of a survey provides a baseline for future measurements and trending. The paper concludes with a discussion of the marketing and organizational implications of incorporating the patient satisfaction survey into the ongoing delivery program for addiction services. PMID:19042522

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

    PubMed Central

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

    2010-01-01

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

  12. Technological advances in the treatment of diabetes mellitus: better bioengineering begets benefits in glucose measurement, the artificial pancreas, and insulin delivery.

    PubMed

    Klonoff, David C

    2003-12-01

    The management of type 1 diabetes is being advanced by innovations in glucose measurement, development of an artificial pancreas, and in alternate routes of insulin delivery. Emerging technologies will allow insulin to be delivered more effectively. In the future, patients with type 1 diabetes will receive insulin in optimal quantities (because of more information about blood glucose values) at optimal times (because of better integration of blood glucose values with appropriate insulin dosages) by way of optimal routes into the body (because of needle-free routes of administration) in order to achieve optimal blood glucose control. Emerging technologies for improved care of patients with type 1 diabetes include: 1. new methods for monitoring glucose, including noninvasive, minimally invasive, continuous, and alternate site measurement technologies; 2. new methods for integrating glucose values and insulin dosages, known as the artificial pancreas; and 3. new routes of insulin administration, including inhaled, oral, buccal, nasal, and transdermal drug delivery systems. These new technologies will facilitate proper treatment of type 1 diabetes and improve the lives of affected patients. PMID:16437014

  13. Combination delivery of Adjudin and Doxorubicin via integrating drug conjugation and nanocarrier approaches for the treatment of drug-resistant cancer cells†

    PubMed Central

    Li, Xu; Gao, Cuixia; Wu, Yupei; Cheng, C-Yan; Xia, Weiliang

    2016-01-01

    Combination therapy has been regarded as a potent strategy to overcome multidrug resistance (MDR). In this study, we adopt Adjudin (ADD), a mitochondria inhibitor, and Doxorubicin (DOX), a common chemo-drug, to treat drug-resistant cancer cells (MCF-7/ADR) in combination. Given the different physico-chemical properties of ADD and DOX, we develop a novel drug formulation (ADD–DOX (M)) by integrating drug conjugation and nanocarrier approaches to realize the co-delivery of the two drugs. We demonstrate the conjugation of ADD and DOX via formation of an acid-sensitive hydrazone bond, and then the encapsulation of ADD–DOX conjugates by DSPE-PEG2000 micelles with high drug encapsulation efficiency and well-controllable drug loading efficiency. The obtained ADD–DOX (M) micelles are found to be stable under physiological conditions, but can rapidly release drugs within acidic environments. Following cellular experiments confirm that ADD–DOX (M) vehicles can be internalized by MCF-7/ADR cancer cells through an endocytic pathway and exist within the moderate acidic endolysosomes, thus accelerating the hydrolysis of ADD–DOX and the release of free ADD and DOX. As a result, the ADD–DOX (M) formulation exhibits an excellent anti-MDR effect. In summary, we for the first time report the combinational use of ADD and DOX with an effective co-delivery strategy for the treatment of MDR cancer cells.

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

    PubMed

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

    2013-07-10

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

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

    PubMed Central

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

    2010-01-01

    Purpose To assess patient navigation (PN) utilization and its impact on treatment interruptions and clinical trial enrollment among American Indian (AI) cancer patients. Methods Between February 2004 and September 2009, 332 AI cancer patients received PN services throughout cancer treatment. The PN program provided culturally-competent navigators to assist patients with navigating cancer therapy, obtaining medications, insurance issues, communicating with medical providers, and travel and lodging logistics. Data on utilization and trial enrollment were prospectively collected. Data for a historical control group of 70 AI patients who did not receive PN services were used to compare treatment interruptions among those undergoing PN during curative radiation therapy (subgroup of 123 patients). Results The median number of contacts with a navigator was 12 (range, 1-119). The median time spent with the navigator at first contact was 40 minutes (range 10-250 min.) and 15 min for subsequent contacts. Patients treated with radiation therapy with curative intent who underwent PN had fewer days of treatment interruption (mean, 1.7 days; 95% CI, 1.1-2.2 days) than historical controls who did not receive PN services (mean, 4.9 days; 95% CI, 2.9-6.9 days). Of the 332 patients, 72 (22%; 95% CI, 17-26%) were enrolled on a clinical treatment trial or cancer control protocol. Conclusions PN was associated with fewer treatment interruptions and relatively high rates of clinical trial enrollment among AI cancer patients compared to national reports. PMID:21656754

  16. Peptide and protein delivery using new drug delivery systems.

    PubMed

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

    2013-01-01

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

  17. Pharmacodynamic and therapeutic investigation of focused ultrasound-induced blood-brain barrier opening for enhanced temozolomide delivery in glioma treatment.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. Treatment of postoperative nausea and vomiting after spinal anesthesia for cesarean delivery: A randomized, double-blinded comparison of midazolam, ondansetron, and a combination

    PubMed Central

    Jabalameli, Mitra; Honarmand, Azim; Safavi, Mohammadreza; Chitsaz, Mohsen

    2012-01-01

    Background: The antiemetic efficacy of midazolam and ondansetron was shown before. The aim of the present study was to compare efficacy of using intravenous midazoalm, ondansetron, and midazolam in combination with ondansetron for treatment of nausea and vomiting after cesarean delivery in parturient underwent spinal anesthesia. Materials and Methods: One hundred thirty two parturients were randomly allocated to one of three groups: group M (n = 44) that received intravenous midazoalm 30 μg/kg; group O (n = 44) that received intravenous ondansetron 8 mg; group MO (n = 44) that received intravenous midazoalm 30 μg/kg combined with intravenous ondansetron 8 mg if patients had vomiting or VAS of nausea ≥ 3 during surgery (after umbilical cord clamping) and 24 hours after that. The incidence and severity of vomiting episodes and nausea with visual analog scale (VAS) > 3 were evaluated at 2 hours, 6 hours, and 24 hours after injection of study drugs. Results: The incidence of nausea was significantly less in group MO compared with group M and group O at 6 hours postoperatively (P = 0.01). This variable was not significantly different in three groups at 2 hours and 24 hours after operation. The severity of nausea and vomiting was significantly different in three groups at 6 hours after operation (P < 0.05). Conclusion: Our study showed that using intravenous midazolam 30 μg/kg in combination with intravenous ondansetron 8 mg was superior to administering single drug in treatment of emetic symptoms after cesarean delivery under spinal anesthesia. PMID:23210061

  20. What is the best treatment for fluctuating Parkinson's disease: continuous drug delivery or deep brain stimulation of the subthalamic nucleus?

    PubMed

    Hilker, Rüdiger; Antonini, Angelo; Odin, Per

    2011-06-01

    Motor complications impair quality of life and cause severe disability in patients with advanced Parkinson's disease (PD). Since they are often refractory to medical therapy, interventional therapies have been developed, which can provide a considerable reduction of daily off-time and dopaminergic dyskinesias. Continuous dopaminergic drug delivery (CDD) is based on the steady stimulation of striatal dopamine receptors by subcutaneous apomorphine or duodenal L: -DOPA infusions via portable minipumps. Advances in the understanding of basal ganglia functioning and in neurosurgical, electrophysiological and neuroimaging techniques have led to a renaissance of neurosurgery for advanced PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the most invasive procedure promising great benefit and the highest level of independency for suitable patients, but is definitely associated with surgical risks and DBS-related side effects. Each of these more or less invasive therapy options has its own profile, and a thorough consideration of its advantages and drawbacks for the individual situation is mandatory. In this paper, we summarize relevant facts for this decision and provide some guidelines for a responsible counseling of eligible patients. PMID:21188435

  1. Targeted delivery of low-dose dexamethasone using PCL-PEG micelles for effective treatment of rheumatoid arthritis.

    PubMed

    Wang, Qin; Jiang, Jiayu; Chen, Wenfei; Jiang, Hao; Zhang, Zhirong; Sun, Xun

    2016-05-28

    Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block-poly (ε-caprolactone) (PCL-PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL-PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL-PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders. PMID:27057749

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2013-07-01

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

  4. Transmucosal delivery of linagliptin for the treatment of type- 2 diabetes mellitus by ultra-thin nanofibers.

    PubMed

    Modgill, Vedant; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2015-01-01

    The objective of the present research was to cultivate an oral formulation of an anti-diabetic drug using polymeric nanofiber. A biodegradable polymer i.e. poly (vinyl alcohol) (PVA) nanofiber loaded linagliptin was prepared using electro spinning technique. The drug entrapment in the developed nanofibers was confirmed by scanning electron microscopy and X-ray diffraction. The in vivo study was performed on male Wistar rats to establish the pharmacodynamics behavior of developed formulation. The mucoadhesive strength results confirmed that the drug loaded PVA nanofiber patch had the highest mucoadhesion strength compare to PVA film and blank PVA nanofiber, due to its higher water holding capacity and surface area. The in vitro release study suggested that controlled release array of the drug from the nanofiber patch. In vivo activity validated the fact that linagliptin was delivered in its active state and showed visible results when compared to the commercial formulation. Additionally an encapsulation efficacy of 92% of the experimental formulation provides sufficient suggestion that the nanofibers serve as an ideal carrier for the delivery of linagliptin via the sublingual route. PMID:25410375

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

    SciTech Connect

    Esch, Ann van; Clermont, Christian; Devillers, Magali; Iori, Mauro; Huyskens, Dominique P.

    2007-10-15

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

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

    PubMed

    Van Esch, Ann; Clermont, Christian; Devillers, Magali; Iori, Mauro; Huyskens, Dominique P

    2007-10-01

    For routine pretreatment verification of innovative treatment techniques such as (intensity modulated) dynamic arc therapy and helical TomoTherapy, an on-line and reliable method would be highly desirable. The present solution proposed by TomoTherapy, Inc. (Madison, WI) relies on film dosimetry in combination with up to two simultaneous ion chamber point dose measurements. A new method is proposed using a 2D ion chamber array (Seven29, PTW, Freiburg, Germany) inserted in a dedicated octagonal phantom, called Octavius. The octagonal shape allows easy positioning for measurements in multiple planes. The directional dependence of the response of the detector was primarily investigated on a dual energy (6 and 18 MV) Clinac 21EX (Varian Medical Systems, Palo Alto, CA) as no fixed angle incidences can be calculated in the Hi-Art TPS of TomoTherapy. The array was irradiated from different gantry angles and with different arc deliveries, and the dose distributions at the level of the detector were calculated with the AAA (Analytical Anisotropic Algorithm) photon dose calculation algorithm implemented in Eclipse (Varian). For validation on the 6 MV TomoTherapy unit, rotational treatments were generated, and dose distributions were calculated with the Hi-Art TPS. Multiple cylindrical ion chamber measurements were used to cross-check the dose calculation and dose delivery in Octavius in the absence of the 2D array. To compensate for the directional dependence of the 2D array, additional prototypes of Octavius were manufactured with built-in cylindrically symmetric compensation cavities. When using the Octavius phantom with a 2 cm compensation cavity, measurements with an accuracy comparable to that of single ion chambers can be achieved. The complete Octavius solution for quality assurance of rotational treatments consists of: The 2D array, two octagonal phantoms (with and without compensation layer), an insert for nine cylindrical ion chambers, and a set of inserts of various tissue equivalent materials of different densities. The combination of the 2D array with the Octavius phantom proved to be a fast and reliable method for pretreatment verification of rotational treatments. Quality control of TomoTherapy patients was reduced to a total of approximately 25 min per patient. PMID:17985628

  7. Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment.

    PubMed

    Saha, Chabita; Kaushik, Agrima; Das, Asmita; Pal, Sandip; Majumder, Debashis

    2016-01-01

    Polymer nanoparticles are vehicles used for delivery of hydrophobic anti-cancer drugs, like doxorubicin, paclitaxel or chemopreventors like quercetin (Q). The present study deals with the synthesis and characterisation of nano formulations (NFs) from Q loaded PLGA (poly lactic-co-glycolic acid) nano particles (NPs) by surface modification. The surface of Q-loaded (NPs) is modified by coating with biopolymers like bovine serum albumin (BSA) or histones (His). Conventional chemotherapeutic drugs adriamycin (ADR) and mitoxantrone (MTX) are bound to BSA and His respectively before being coated on Q-loaded NPs to nano formulate NF1 and NF2 respectively. The sizes of these NFs are in the range 400-500 nm as ascertained by SEM and DLS measurements. Encapsulation of Q in polymer NPs is confirmed from shifts in FT-IR, TGA and DSC traces of Q-loaded NPs compared to native PLGA and Q. Surface modification in NFs is evidenced by three distinct regions in their TEM images; the core, polymer capsule and the coated surface. Negative zeta potential of Q-loaded NPs shifted to positive potential on surface modification in NF1 and NF2. In vitro release of Q from the NFs lasted up to twenty days with an early burst release. NF2 is better formulation than NF1 as loading of MTX is 85% compared to 23% loading of ADR. Such NFs are expected to overcome multi-drug resistance (MDR) by reaching and treating the target cancerous cells by virtue of size, charge and retention. PMID:27196562

  8. Probiotics for the prevention and treatment of allergies, with an emphasis on mode of delivery and mechanism of action.

    PubMed

    Prakash, Satya; Tomaro-Duchesneau, Catherine; Saha, Shyamali; Rodes, Laetitia; Kahouli, Imen; Malhotra, Meenakshi

    2014-01-01

    Allergy, also termed type I hypersensitivity, is defined as a "disease following a response by the immune system to an otherwise innocuous antigen". The prevalence of allergies is high and escalating, with almost half the populations of North America and Europe having allergies to one or more common environmental antigens. Although rarely life-threatening allergies cause much distress and pose an important economic burden. Recent studies demonstrate the importance of the commensal bacteria of the gastrointestinal tract, termed the microbiota, in stimulating and modulating the immune system. This goes hand-in-hand with the hygiene hypothesis, proposed by Strachan in 1989. With this in mind, the use of pre- and probiotics has gained interest to prevent and treat allergies through modulation of the gut microbiota and the immune system. Probiotics, namely Lactobacilli and Bifidobacteria, are live microorganisms that can be incorporated in the diet in the form of functional foods or dietary supplements to beneficially influence the host. In recent studies, probiotic formulations demonstrated the capability to successfully modulate allergic rhinitis, atopic disorders and food-related allergies. A number of probiotic mechanisms of action are involved in controlling hypersensitivity responses, many of which are still not yet understood. Microencapsulation has gained importance as a device for the oral delivery of probiotic cells and may play an important role in the development of a successful probiotic formulation to treat and prevent allergies. Despite the promising research on probiotic biotherapeutics, further investigations are required to develop a successful therapeutic to treat and prevent allergies. PMID:23701572

  9. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug release property to achieve increased therapeutic efficacy and reduced side effects. Nanoparticles and nanoliposomes are emerging areas of nanotechnologies that have already begun to make an impact over new modalities for cancer chemotherapy, diagnosis as well as gene delivery. Presently it is possible to reduce the particle size in such a way that the particles can be easily injected or inhaled and many types of human cells are capable to internalize them. A number of fabrications such as PEGylation, specific antibody conjugation, aptamer ligation, specific ligand binding etc. on the nanosize delivery devices makes them in the streamline of research to particularly target the diseased cells thus avoiding the healthy one. Potential of nanosize carriers to cross the blood brain barrier encourages us to build up a new strategy for delivery of therapeutically active agents to the brain. Nanotechnology is showing an emerging effect in chronic diseases such as diabetes, cancer, neurodegenerative diseases etc. Nanosize vaccines are having greater effect in production of better immunity against pathogens through direct administration of medication to the specialized dendritic cells in the immune systems. Lots of hopes and speculations are reigning around the scientists with nanosize drug delivery systems that may revolutionize the drug delivery with the better understanding of drug action mechanism and identification of biomarker associated with specific diseases. Nanosize drug delivery systems are emerging with the promising strategies for efficient targeted drug delivery. The proper designing of these systems can make them capable for being independent in the normal tissue environments and selective at the diseased pharmacological site. Nanomaterials as formulations are already in the market or in clinical trials. Investigation on nanostructural drug delivery is a highly growing field today as an extensive amount of research is on with an expectation to open up new avenues to drug delivery. No doubt the next era of drug therapy will be greater influenced by nanoscale drug delivery systems. However these newer systems for delivery of bioactive molecules must be reliable, efficient and safe. PMID:25106648

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    PubMed

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

    2011-05-01

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

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

    PubMed Central

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

    2015-01-01

    Objective To evaluate the efficacy and safety of AVP-825, a drug–device combination of low-dose sumatriptan powder (22 mg loaded dose) delivered intranasally through a targeted Breath Powered device vs an identical device containing lactose powder (placebo device) in the treatment of migraine headache. Background Early treatment of migraine headaches is associated with improved outcome, but medication absorption after oral delivery may be delayed in migraineurs because of reduced gastric motility. Sumatriptan powder administered with an innovative, closed-palate, Bi-Directional, Breath Powered intranasal delivery mechanism is efficiently absorbed across the nasal mucosa and produces fast absorption into the circulation. Results from a previously conducted placebo-controlled study of AVP-825 showed a high degree of headache relief with an early onset of action (eg, 74% AVP-825 vs 38% placebo device at 1 hour, P < .01). Methods In this double-blind, placebo-controlled, parallel-group study in adults with a history of migraine with or without aura, participants were randomized via computer-generated lists to AVP-825 or placebo device to treat a single migraine headache of moderate or severe intensity. The primary endpoint was headache relief (defined as reduction of headache pain intensity from severe or moderate migraine headache to mild or none) at 2 hours post-dose. Results Two hundred and thirty patients (116 AVP-825 and 114 placebo device) were randomized, of whom 223 (112 and 111, respectively) experienced a qualifying migraine headache (their next migraine headache that reached moderate or severe intensity). A significantly greater proportion of AVP-825 patients reported headache relief at 2 hours post-dose compared with those using the placebo device (68% vs 45%, P = .002, odds ratio 2.53, 95% confidence interval [1.45, 4.42]). Between-group differences in headache relief were evident as early as 15 minutes, reached statistical significance at 30 minutes post-dose (42% vs 27%, P = .03), and were sustained at 24 hours (44% vs 24%, P = .002) and 48 hours (34% vs 20%, P = .01). Thirty-four percent of patients treated with AVP-825 were pain-free at 2 hours compared with 17% using the placebo device (P = .008). More AVP-825 patients reported meaningful pain relief (patient interpretation) of migraine within 2 hours of treatment vs placebo device (70% vs 45%, P < .001), and fewer required rescue medication (37% vs 52%, P = .02). Total migraine freedom (patients with no headache, nausea, phonophobia, photophobia, or vomiting) reached significance following treatment with AVP-825 at 1 hour (19% vs 9%; P = .04). There were no serious adverse events (AEs), and no systemic AEs occurred in more than one patient. Chest pain or pressure was not reported, and only one patient taking AVP-825 reported mild paresthesia. No other triptan sensations were reported. Conclusions Targeted delivery of a low-dose of sumatriptan powder via a novel, closed-palate, Breath Powered, intranasal device (AVP-825) provided fast relief of moderate or severe migraine headache in adults that reached statistical significance over placebo by 30 minutes. The treatment was well tolerated with a low incidence of systemic AEs. PMID:25355310

  14. Highly accurate nephelometric titrimetry.

    PubMed

    Zhan, Xiancheng; Li, Chengrong; Li, Zhiyi; Yang, Xiucen; Zhong, Shuguang; Yi, Tao

    2004-02-01

    A method that accurately indicates the end-point of precipitation reactions by the measurement of the relative intensity of the scattered light in the titrate is presented. A new nephelometric titrator with an internal nephelometric sensor has been devised. The work of the titrator including the sensor and change in the turbidity of the titrate and intensity of the scattered light are described. The accuracy of the nephelometric titrimetry is discussed theoretically. The titration of NaCl with AgNO(3) serves as a model. A relative error as well as deviation is within 0.2% under the experimental conditions. The applicability of the titrimetry in pharmaceutical analyses, for example, phenytoin sodium and procaine hydrochloride, is generally illustrated. PMID:14705200

  15. Accurate Inclusion Mass Screening

    PubMed Central

    Jaffe, Jacob D.; Keshishian, Hasmik; Chang, Betty; Addona, Theresa A.; Gillette, Michael A.; Carr, Steven A.

    2008-01-01

    Verification of candidate biomarker proteins in blood is typically done using multiple reaction monitoring (MRM) of peptides by LC-MS/MS on triple quadrupole MS systems. MRM assay development for each protein requires significant time and cost, much of which is likely to be of little value if the candidate biomarker is below the detection limit in blood or a false positive in the original discovery data. Here we present a new technology, accurate inclusion mass screening (AIMS), designed to provide a bridge from unbiased discovery to MS-based targeted assay development. Masses on the software inclusion list are monitored in each scan on the Orbitrap MS system, and MS/MS spectra for sequence confirmation are acquired only when a peptide from the list is detected with both the correct accurate mass and charge state. The AIMS experiment confirms that a given peptide (and thus the protein from which it is derived) is present in the plasma. Throughput of the method is sufficient to qualify up to a hundred proteins/week. The sensitivity of AIMS is similar to MRM on a triple quadrupole MS system using optimized sample preparation methods (low tens of ng/ml in plasma), and MS/MS data from the AIMS experiments on the Orbitrap can be directly used to configure MRM assays. The method was shown to be at least 4-fold more efficient at detecting peptides of interest than undirected LC-MS/MS experiments using the same instrumentation, and relative quantitation information can be obtained by AIMS in case versus control experiments. Detection by AIMS ensures that a quantitative MRM-based assay can be configured for that protein. The method has the potential to qualify large number of biomarker candidates based on their detection in plasma prior to committing to the time- and resource-intensive steps of establishing a quantitative assay. PMID:18534968

  16. Accurate quantum chemical calculations

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  18. Sci—Thur PM: Planning and Delivery — 02: Treatment planning workflow for very high-energy electron beam radiotherapy

    SciTech Connect

    Bazalova, Magdalena; Qu, Bradley; Palma, Bianey; Maxim, Peter; Loo, Billy; Hårdemark, Bjorn; Hynning, Elin

    2014-08-15

    Purpose: To develop treatment planning workflow for rapid radiotherapy delivered with very-high energy electron (VHEE) scanning beam. Methods: VHEE radiotherapy treatment planning was performed by linking Monte Carlo (MC) dose calculations with inverse optimization in a research version of RayStation. In order to study a number of treatment parameters, a Matlab graphical user interface (GUI) for calculation of VHEE beamlet dose was developed. Through the GUI, EGSnrc MC simulations were run for a number of beam energies, number of beams, beamlet spot and grid sizes, and machine bore sizes. VHEE plans for a pediatric patient with a 4.3 cm{sup 3} brain target optimized with spot-scanning algorithm in RayStation were compared to the clinically delivered 6 MV VMAT plan. Results and Discussion: VHEE beam energy had the largest effect on the quality of dose distributions. For the same target dose, the mean doses to critical organs decreased by 10–15% when planned with 100 MeV compared to 60 MeV. VHEE plans calculated with 36 beams outperformed plans calculated with 13 and 17 beams. While beamlet spacing and bore size had a small effect on VHEE dose distributions, 0.1-3mm beamlet sizes resulted in identical dose distributions. Critical organ doses were by up to 70% lower in the best VHEE plan compared to the clinical 6 MV VMAT plan. Conclusions: We have developed a GUI for MC beamlet generation for treatment planning of VHEE radiotherapy. We have demonstrated that pediatric VHEE plans resulted in significant critical organ dose sparing compared to the clinical VMAT plan.

  19. Early results of prostate cancer radiation therapy: an analysis with emphasis on research strategies to improve treatment delivery and outcomes

    PubMed Central

    2013-01-01

    Background There is scant data regarding disease presentation and treatment response among black men living in Africa. In this study we evaluate disease presentation and early clinical outcomes among Ghanaian men with prostate cancer treated with external beam radiotherapy (EBRT). Methods A total of 379 men with prostate cancer were referred to the National Center for Radiotherapy, Ghana from 2003 to 2009. Data were collected regarding patient-and tumor-related factors such as age, prostate specific antigen (PSA), Gleason score (GS), clinical stage (T), and use of androgen deprivation therapy (ADT). For patients who received EBRT, freedom from biochemical failure (FFbF) was evaluated using the Kaplan-Meier method. Results Of 379 patients referred for treatment 69.6% had initial PSA (iPSA) >?20 ng/ml, and median iPSA was 39.0 ng/ml. A total of 128 men, representing 33.8% of the overall cohort, were diagnosed with metastatic disease at time of referral. Among patients with at least 2 years of follow-up after EBRT treatment (n=52; median follow-up time: 38.9 months), 3- and 5-year actuarial FFbF was 73.8% and 65.1% respectively. There was significant association between higher iPSA and GS (810 vs. ?7, p < 0.001), and T stage (T3/4 vs. T1/2, p < 0.001). Conclusions This is the largest series reporting on outcomes after prostate cancer treatment in West Africa. That one-third of patients presented with metastatic disease suggests potential need for earlier detection to permit curative-intent therapy. Data from this study will aid in the strategic development of prostate cancer research roadmap in Ghana. PMID:23324165

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

    PubMed

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

    2013-12-15

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

  1. Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle

    PubMed Central

    Wang, Wen; Song, Yunmei; Petrovski, Kiro; Eats, Patricia; Trott, Darren J; Wong, Hui San; Page, Stephen W; Perry, Jeanette; Garg, Sanjay

    2015-01-01

    Background Mastitis is a major disease of dairy cattle. Given the recent emergence of methicillin-resistant Staphylococcus aureus as a cause of bovine mastitis, new intramammary (IMA) treatments are urgently required. Lasalocid, a member of the polyether ionophore class of antimicrobial agents, has not been previously administered to cows by the IMA route and has favorable characteristics for development as a mastitis treatment. This study aimed to develop an IMA drug delivery system (IMDS) of lasalocid for the treatment of bovine mastitis. Methods Minimum inhibitory concentrations (MICs) were determined applying the procedures recommended by the Clinical and Laboratory Standards Institute. Solid dispersions (SDs) of lasalocid were prepared and characterized using differential scanning calorimetry and Fourier transform infrared spectroscopy. IMDSs containing lasalocid of micronized, nano-sized, or as SD form were tested for their IMA safety in cows. Therapeutic efficacy of lasalocid IMDSs was tested in a bovine model involving experimental IMA challenge with the mastitis pathogen Streptococcus uberis. Results Lasalocid demonstrated antimicrobial activity against the major Gram-positive mastitis pathogens including S. aureus (MIC range 0.5–8 μg/mL). The solubility test confirmed limited, ion-strength-dependent water solubility of lasalocid. A kinetic solubility study showed that SDs effectively enhanced water solubility of lasalocid (21–35-fold). Polyvinylpyrrolidone (PVP)-lasalocid SD caused minimum mammary irritation in treated cows and exhibited faster distribution in milk than either nano or microsized lasalocid. IMDSs with PVP-lasalocid SD provided effective treatment with a higher mastitis clinical and microbiological cure rate (66.7%) compared to cloxacillin (62.5%). Conclusion Lasalocid SD IMDS provided high cure rates and effectiveness in treating bovine mastitis with acceptable safety in treated cows. PMID:25653501

  2. Sensitivity of an Elekta iView GT a-Si EPID model to delivery errors for pre-treatment verification of IMRT fields.

    PubMed

    Herwiningsih, Sri; Hanlon, Peta; Fielding, Andrew

    2014-12-01

    A Monte Carlo model of an Elekta iViewGT amorphous silicon electronic portal imaging device (a-Si EPID) has been validated for pre-treatment verification of clinical IMRT treatment plans. The simulations involved the use of the BEAMnrc and DOSXYZnrc Monte Carlo codes to predict the response of the iViewGT a-Si EPID model. The predicted EPID images were compared to the measured images obtained from the experiment. The measured EPID images were obtained by delivering a photon beam from an Elekta Synergy linac to the Elekta iViewGT a-Si EPID. The a-Si EPID was used with no additional build-up material. Frame averaged EPID images were acquired and processed using in-house software. The agreement between the predicted and measured images was analyzed using the gamma analysis technique with acceptance criteria of 3 %/3 mm. The results show that the predicted EPID images for four clinical IMRT treatment plans have a good agreement with the measured EPID signal. Three prostate IMRT plans were found to have an average gamma pass rate of more than 95.0 % and a spinal IMRT plan has the average gamma pass rate of 94.3 %. During the period of performing this work a routine MLC calibration was performed and one of the IMRT treatments re-measured with the EPID. A change in the gamma pass rate for one field was observed. This was the motivation for a series of experiments to investigate the sensitivity of the method by introducing delivery errors, MLC position and dosimetric overshoot, into the simulated EPID images. The method was found to be sensitive to 1 mm leaf position errors and 10 % overshoot errors. PMID:25182667

  3. Nucleolin-targeting liposomes guided by aptamer AS1411 for the delivery of siRNA for the treatment of malignant melanomas.

    PubMed

    Li, Liyu; Hou, Jianjun; Liu, Xinjie; Guo, Yujia; Wu, Yun; Zhang, Lihe; Yang, Zhenjun

    2014-04-01

    BRAF gene mutation is found in more than 60% of malignant melanomas, which are difficult to treat. In this study, a new tumor-targeting liposome was developed to deliver anti-BRAF siRNA (siBraf) for the treatment of melanomas. Nucleolin is overexpressed on the surface of cancer cells. AS1411, an aptamer showing specific binding to nucleolin, was conjugated to PEGylated cationic liposome as the targeting probe ASLP (AS1411-PEG-liposome). The ASLP/siRNA complex was formed through electrostatic interaction between ASLP and siRNA. The binding of AS1411 to the surface of PEGylated liposomes was confirmed by gel electrophoresis and capillary electrophoresis. Real-time PCR and Western blot analysis showed that ASLP/siBraf exhibited strong silencing activity of BRAF gene. The much higher accumulation of the siRNA in tumor cells comparing with normal cells indicated that ASLP displayed excellent tumor-targeting capability. Notably, ASLP/siBraf showed significant silencing activity in A375 tumor xenograft mice and inhibited the melanoma growth. These results suggested that the new nucleolin-targeted siRNA delivery system by AS1411 may have the potential for the treatment of melanoma. PMID:24486214

  4. Forelimb Treatment in a Large Cohort of Dystrophic Dogs Supports Delivery of a Recombinant AAV for Exon Skipping in Duchenne Patients

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. Topical delivery and in vivo antileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis.

    PubMed

    Carneiro, Guilherme; Santos, Delia C M; Oliveira, Monica C; Fernandes, Ana P; Ferreira, Luciana S; Ramaldes, Gilson A; Nunan, Elziria A; Ferreira, Lucas A M

    2010-03-01

    The present study aimed to evaluate the potential of liposomes loaded with paromomycin (PA), an aminoglycoside antibiotic associated with poor skin penetration, for the topical treatment of cutaneous leishmaniasis (CL). Fluid liposomes were prepared and characterized for particle size, zeta potential, and drug entrapment. Permeation studies were performed with two in vitro models: intact and stripped skin. The antileishmanial activity of free and liposomal PA was evaluated in BALB/c mice infected by Leishmania (L.) major. Drug entrapment ranged from 10 to 14%, and the type of vesicle had little influence on this parameter. Particle size and polydispersity index of the vesicles composed by phosphatidylcholine (PC) and PC/cholesterol (Chol) ranged from of 516 to 362 nm and 0.7 to 0.4, respectively. PA permeation across intact skin was low, regardless of the formulation tested, while drug penetration into skin (percent of the applied dose) from PC (7.2 +/- 0.2%) and PC/Chol (4.8 +/- 0.2%) liposomes was higher than solution (1.9 +/- 0.1%). PA-loaded liposomes enhanced in vitro drug permeation across stripped skin and improved the in vivo antileishmanial activity in experimentally infected mice. Our findings suggest that the liposomes represent a promising alternative for the topical treatment of CL using PA. PMID:19530897

  7. Taking stock: A multistakeholder perspective on improving the delivery of care and the development of treatments for Alzheimer's disease.

    PubMed

    Bradley, Patrick; Akehurst, Ron; Ballard, Clive; Banerjee, Sube; Blennow, Kaj; Bremner, Jennifer; Broich, Karl; Cummings, Jeffrey; Dening, Karen; Dubois, Bruno; Klipper, Wiebke; Leibman, Chris; Mantua, Valentina; Molinuevo, José Luis; Morgan, Susan; Muscolo, Luisa A A; Nicolas, François; Pani, Luca; Robinson, Louise; Siviero, Paolo; van Dam, Julius; Van Emelen, Jan; Wimo, Anders; Wortmann, Marc; Goh, Lindee

    2015-04-01

    Health-care stakeholders increasingly recognize that the scientific and economic challenges associated with Alzheimer's disease (AD) are simply too great for individual stakeholder groups to address solely from within their own silos. In the necessary spirit of collaboration, we present in this perspective a set of multicountry multistakeholder recommendations to improve the organization of existing AD and dementia care and the development of new treatments. In brief, the five recommendations are (1) health-care systems must make choices regarding the patient populations to be diagnosed and treated, (2) health-care systems should use an evidence-based standard of care, (3) increased collaboration between public and private institutions is needed to enhance research, (4) reimbursement end points need to be agreed on and validated, and (5) innovative business models should be used to spur the introduction of new medicines. PMID:24751826

  8. Therapeutic applications of hydrogels in oral drug delivery

    PubMed Central

    Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

    2015-01-01

    Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

  9. Rotational IMRT delivery using a digital linear accelerator in very high dose rate 'burst mode'

    NASA Astrophysics Data System (ADS)

    Salter, Bill J.; Sarkar, Vikren; Wang, Brian; Shukla, Himanshu; Szegedi, Martin; Rassiah-Szegedi, Prema

    2011-04-01

    Recently, there has been a resurgence of interest in arc-based IMRT, through the use of 'conventional' multileaf collimator (MLC) systems that can treat large tumor volumes in a single, or very few pass(es) of the gantry. Here we present a novel 'burst mode' modulated arc delivery approach, wherein 2000 monitor units per minute (MU min-1) high dose rate bursts of dose are facilitated by a flattening-filter-free treatment beam on a Siemens Artiste (Oncology Care Systems, Siemens Medical Solutions, Concord, CA, USA) digital linear accelerator in a non-clinical configuration. Burst mode delivery differs from continuous mode delivery, used by Elekta's VMAT (Elekta Ltd, Crawley, UK) and Varian's RapidArc (Varian Medical Systems, Palo Alto, CA, USA) implementations, in that dose is not delivered while MLC leaves are moving. Instead, dose is delivered in bursts over very short arc angles and only after an MLC segment shape has been completely formed and verified by the controller. The new system was confirmed to be capable of delivering a wide array of clinically relevant treatment plans, without machine fault or other delivery anomalies. Dosimetric accuracy of the modulated arc platform, as well as the Prowess (Prowess Inc., Concord, CA, USA) prototype treatment planning version utilized here, was quantified and confirmed, and delivery times were measured as significantly brief, even with large hypofractionated doses. The burst mode modulated arc approach evaluated here appears to represent a capable, accurate and efficient delivery approach.

  10. Rotational IMRT delivery using a digital linear accelerator in very high dose rate 'burst mode'.

    PubMed

    Salter, Bill J; Sarkar, Vikren; Wang, Brian; Shukla, Himanshu; Szegedi, Martin; Rassiah-Szegedi, Prema

    2011-04-01

    Recently, there has been a resurgence of interest in arc-based IMRT, through the use of 'conventional' multileaf collimator (MLC) systems that can treat large tumor volumes in a single, or very few pass(es) of the gantry. Here we present a novel 'burst mode' modulated arc delivery approach, wherein 2000 monitor units per minute (MU min(-1)) high dose rate bursts of dose are facilitated by a flattening-filter-free treatment beam on a Siemens Artiste (Oncology Care Systems, Siemens Medical Solutions, Concord, CA, USA) digital linear accelerator in a non-clinical configuration. Burst mode delivery differs from continuous mode delivery, used by Elekta's VMAT (Elekta Ltd, Crawley, UK) and Varian's RapidArc (Varian Medical Systems, Palo Alto, CA, USA) implementations, in that dose is not delivered while MLC leaves are moving. Instead, dose is delivered in bursts over very short arc angles and only after an MLC segment shape has been completely formed and verified by the controller. The new system was confirmed to be capable of delivering a wide array of clinically relevant treatment plans, without machine fault or other delivery anomalies. Dosimetric accuracy of the modulated arc platform, as well as the Prowess (Prowess Inc., Concord, CA, USA) prototype treatment planning version utilized here, was quantified and confirmed, and delivery times were measured as significantly brief, even with large hypofractionated doses. The burst mode modulated arc approach evaluated here appears to represent a capable, accurate and efficient delivery approach. PMID:21364260

  11. A novel endoscopic delivery system for placement of a duodenal-jejunal implant for the treatment of obesity and type 2 diabetes.

    PubMed

    Fishman, Ezra; Melanson, Dave; Lamport, Ron; Levine, Andy

    2008-01-01

    The EndoBarrier Delivery System is a unique product capable of reliably delivering an implant into the small intestine. Further improvements to the product can likely be made to facilitate tracking and improved navigation through the small bowel. This unique system and its related technology may have additional applications where access to the small bowel is desired such as drug delivery, diagnostic and therapeutic endoscopy and small bowel stent delivery. PMID:19163211

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

    PubMed

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

    2015-04-01

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

  13. Thermosensitive chitosan-based hydrogel as a topical ocular drug delivery system of latanoprost for glaucoma treatment.

    PubMed

    Cheng, Yung-Hsin; Tsai, Tung-Hu; Jhan, Yong-Yu; Chiu, Allen Wen-Hsiang; Tsai, Kun-Ling; Chien, Chian-Shiu; Chiou, Shih-Hwa; Liu, Catherine Jui-Lin

    2016-06-25

    Ocular hypertension is a major risk factor for the development and progression of glaucoma. Frequent and long-term application of latanoprost often causes undesirable local side effects, which are a major cause of therapeutic failure due to loss of persistence in using this glaucoma medical therapy. In the present study, we developed a thermosensitive chitosan-based hydrogel as a topical eye drop formulation for the sustained release of latanoprost to control ocular hypertension. The developed formulation without preservatives may improve compliance and possibly even efficacy. The results of this study support its biocompatibility and sustained-release profile both in vitro and in vivo. After topical application of latanoprost-loaded hydrogel, triamcinolone acetonide-induced elevated intraocular pressure was significantly decreased within 7 days and remained at a normal level for the following 21 days in rabbit eyes. This newly developed chitosan-based hydrogel may provide a non-invasive alternative to traditional anti-glaucoma eye drops for glaucoma treatment. PMID:27083831

  14. Direct chemotherapeutic dual drug delivery through intra-articular injection for synergistic enhancement of rheumatoid arthritis treatment

    PubMed Central

    Reum Son, A; Kim, Da Yeon; Hun Park, Seung; Yong Jang, Ja; Kim, Kyungsook; Ju Kim, Byoung; Yun Yin, Xiang; Ho Kim, Jae; Hyun Min, Byoung; Keun Han, Dong; Suk Kim, Moon

    2015-01-01

    The effectiveness of systemic rheumatoid arthritis (RA) treatments is limited by difficulties in achieving therapeutic doses within articular joints. We evaluated the ability of intra-articular administration of injectable formulations to synergistically enhance repair of RA joints. Methotrexate-loaded hyaluronic acid (Met-HA), dexamethasone-loaded microcapsules (Dex-M), and Dex-M dispersed inside Met-HA were prepared as viscous emulsions and injected into articular joints using a needle to form a drug depot. By near-infrared (NIR) fluorescence imaging, we confirmed the local release of NIR from the depot injected into the articular joint over an extended period. In comparison with the subjects treated with Met-HA or Dex-M alone, subjects treated simultaneously with Met-HA and Dex-M exhibited faster and more significant RA repair. Collectively, these results indicated that the drug depot formed after intra-articular injection of Met-HA/Dex-M induced long-lasting drug release and allowed Met and Dex to effectively act in the articular joint, resulting in enhanced RA repair. PMID:26424611

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

    PubMed Central

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

    2014-01-01

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

  16. Sci—Thur PM: Planning and Delivery — 03: Automated delivery and quality assurance of a modulated electron radiation therapy plan

    SciTech Connect

    Connell, T; Papaconstadopoulos, P; Alexander, A; Serban, M; Devic, S; Seuntjens, J

    2014-08-15

    Modulated electron radiation therapy (MERT) offers the potential to improve healthy tissue sparing through increased dose conformity. Challenges remain, however, in accurate beamlet dose calculation, plan optimization, collimation method and delivery accuracy. In this work, we investigate the accuracy and efficiency of an end-to-end MERT plan and automated-delivery workflow for the electron boost portion of a previously treated whole breast irradiation case. Dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. The automated delivery, which covered 4 electron energies, 196 subfields and 6183 total MU was completed in 25.8 minutes, including 6.2 minutes of beam-on time with the remainder of the delivery time spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. The delivery time could be reduced by 5.3 minutes with minor electron collimator modifications and the beam-on time could be reduced by and estimated factor of 2–3 through redesign of the scattering foils. Comparison of the planned and delivered film dose gave 3%/3 mm gamma pass rates of 62.1, 99.8, 97.8, 98.3, and 98.7 percent for the 9, 12, 16, 20 MeV, and combined energy deliveries respectively. Good results were also seen in the delivery verification performed with a MapCHECK 2 device. The results showed that accurate and efficient MERT delivery is possible with current technologies.

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

    SciTech Connect

    Shaitelman, Simona F.; Kim, Leonard H.; Yan Di; Martinez, Alvaro A.; Vicini, Frank A.; Grills, Inga S.

    2011-07-01

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

  18. Nanomedicine in pulmonary delivery

    PubMed Central

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

    2009-01-01

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

  19. Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

    PubMed Central

    2012-01-01

    Background Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS?+?SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS?+?SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p?treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected. PMID:22545573

  20. A Targeted DNAzyme-Nanocomposite Probe Equipped with Built-in Zn(2+) Arsenal for Combined Treatment of Gene Regulation and Drug Delivery.

    PubMed

    He, Zhi-Mei; Zhang, Peng-Hui; Li, Xin; Zhang, Jian-Rong; Zhu, Jun-Jie

    2016-01-01

    As catalytic nucleic acids, DNAzymes have been extensively used in the design of sensing platforms. However, their potentials as intelligent drug carriers for responsive drug release in gene therapy and chemotherapy were rarely explored. Herein, we report a dual-functional probe composed of gold nanoparticles (GNPs), catalytic Zn(2+)-dependent DNAzyme, anticancer drug doxorubicin (Dox), targeted AS1411 aptamer and acid-decomposable ZnO quantum dots (ZnO QDs) to achieve intracellular gene regulation and drug delivery in a controlled manner. By means of aptamer-guided targeting and receptor-mediated endocytosis, the probes were specifically internalized into the HeLa cells and trapped in the acidic endo-/lysosomes, where the ZnO QDs as the built-in Zn(2+) arsenal were promptly dissolved to offer Zn(2+), leading to the activation of DNAzyme to cleave the substrate strands, and subsequent drug release. Meanwhile, as designed, one part of the cleaved substrate, hybridized with the overexpressed miR-21 in the target cells, thereby declining its intracellular level. Taken together, the down-regulation of miR-21 has a synergistic effect with Dox to efficiently eradicate the cancer cells. Thus, the favorable biocompatibility, cancer cell specificity and combined treatment make the probe promising for therapy of multidrug-resistant cancer and in vivo application. PMID:26956167

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

    PubMed Central

    2012-01-01

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

  2. Treatment with low-temperature atmospheric pressure plasma enhances cutaneous delivery of epidermal growth factor by regulating E-cadherin-mediated cell junctions.

    PubMed

    Choi, Jeong-Hae; Nam, Seoul-Hee; Song, Yeon-Suk; Lee, Hyun-Wook; Lee, Hae-June; Song, Kiwon; Hong, Jin-Woo; Kim, Gyoo-Cheon

    2014-09-01

    The barrier system of the skin not only defends against antigens and harmful substances, but also hinders the permeation of medicines and cosmetics into the dermis. Several strategies have been developed to enhance the absorption ability of skin, including the use of chemicals and skin ablation devices. However, the cost and inconvenience of these strategies highlights the need for a novel and safe method for increasing skin absorption. In this study, we examined the effect of low temperature atmospheric pressure plasma (LTAPP) on the efficiency of drug penetration through the skin, as well as its mechanism of action. HaCaT human keratinocytes and hairless mice were exposed to LTAPP treatment, and the cellular and tissue gene expression, and morphological changes were monitored. We found that the LTAPP exposure reduced the expression of E-cadherin in skin cells and led to the loss of cell-cell contacts. The exposure of mouse skin to LTAPP also reduced the expression of E-cadherin and prevented intercellular junction formation within the tissue, leading to enhanced absorption of hydrophilic agents, eosin and epidermal growth factor. The reduction in E-cadherin expression and reduced skin barrier function recovered completely within 3 h of LTAPP exposure. Taken together, these data show that LTAPP can induce a temporal decrease in the skin barrier function by regulating E-cadherin-mediated intercellular interactions, leading to the enhanced transdermal delivery of drugs and cosmetics. PMID:24728827

  3. A Targeted DNAzyme-Nanocomposite Probe Equipped with Built-in Zn2+ Arsenal for Combined Treatment of Gene Regulation and Drug Delivery

    PubMed Central

    He, Zhi-Mei; Zhang, Peng-Hui; Li, Xin; Zhang, Jian-Rong; Zhu, Jun-Jie

    2016-01-01

    As catalytic nucleic acids, DNAzymes have been extensively used in the design of sensing platforms. However, their potentials as intelligent drug carriers for responsive drug release in gene therapy and chemotherapy were rarely explored. Herein, we report a dual-functional probe composed of gold nanoparticles (GNPs), catalytic Zn2+-dependent DNAzyme, anticancer drug doxorubicin (Dox), targeted AS1411 aptamer and acid-decomposable ZnO quantum dots (ZnO QDs) to achieve intracellular gene regulation and drug delivery in a controlled manner. By means of aptamer-guided targeting and receptor-mediated endocytosis, the probes were specifically internalized into the HeLa cells and trapped in the acidic endo-/lysosomes, where the ZnO QDs as the built-in Zn2+ arsenal were promptly dissolved to offer Zn2+, leading to the activation of DNAzyme to cleave the substrate strands, and subsequent drug release. Meanwhile, as designed, one part of the cleaved substrate, hybridized with the overexpressed miR-21 in the target cells, thereby declining its intracellular level. Taken together, the down-regulation of miR-21 has a synergistic effect with Dox to efficiently eradicate the cancer cells. Thus, the favorable biocompatibility, cancer cell specificity and combined treatment make the probe promising for therapy of multidrug-resistant cancer and in vivo application. PMID:26956167

  4. Hyaluronic acid co-functionalized gold nanoparticle complex for the targeted delivery of metformin in the treatment of liver cancer (HepG2 cells).

    PubMed

    Kumar, C Senthil; Raja, M D; Sundar, D Sathish; Gover Antoniraj, M; Ruckmani, K

    2015-09-01

    In this study, green synthesis of gold nanoparticles (AuNPs) was achieved using the extract of eggplant as a reducing agent. Hyaluronic acid (HA) serves as a capping and targeting agent. Metformin (MET) was successfully loaded on HA capped AuNPs (H-AuNPs) and this formulation binds easily on the surface of the liver cancer cells. The synthesized nanoparticles were characterized by UV-Vis spectrophotometer, HR-TEM, particle size analyser and zeta potential measurement. Toxicity studies of H-AuNPs in zebra fish confirmed the in vivo safety of the AuNPs. The in vitro cytotoxicity results showed that the amount of MET-H-AuNPs enough to achieve 50% inhibition (IC50) was much lower than free MET. Flow cytometry analysis showed the significant reduction in G2/M phase after treatment with MET-H-AuNPs, and molecular level apoptosis were studied using western blotting. The novelty of this study is the successful synthesis of AuNPs with a higher MET loading and this formulation exhibited better targeted delivery as well as increased regression activity than free MET in HepG2 cells. PMID:26005140

  5. Expanding Alternative Delivery Systems.

    ERIC Educational Resources Information Center

    Baltzer, Jan A.

    Alternative educational delivery systems that might be useful to community colleges are considered. The following categories of delivery systems are covered: broadcast delivery systems; copy delivery systems, print delivery systems, computer delivery systems, telephone delivery systems, and satellites. Among the applications for broadcast…

  6. Delivery parameter variations and early clinical outcomes of volumetric modulated arc therapy for 31 prostate cancer patients: an intercomparison of three treatment planning systems.

    PubMed

    Tsutsumi, Shinichi; Hosono, Masako N; Tatsumi, Daisaku; Miki, Yoshitaka; Masuoka, Yutaka; Ogino, Ryo; Ishii, Kentaro; Shimatani, Yasuhiko; Miki, Yukio

    2013-01-01

    We created volumetric modulated arc therapy (VMAT) plans for 31 prostate cancer patients using one of three treatment planning systems (TPSs)--ERGO++, Monaco, or Pinnacle--and then treated those patients. A dose of 74 Gy was prescribed to the planning target volume (PTV). The rectum, bladder, and femur were chosen as organs at risk (OARs) with specified dose-volume constraints. Dose volume histograms (DVHs), the mean dose rate, the beam-on time, and early treatment outcomes were evaluated and compared. The DVHs calculated for the three TPSs were comparable. The mean dose rates and beam-on times for Ergo++, Monaco, and SmartArc were, respectively, 174.3 ± 17.7, 149.7 ± 8.4, and 185.8 ± 15.6 MU/min and 132.7 ± 8.4, 217.6 ± 13.1, and 127.5 ± 27.1 sec. During a follow-up period of 486.2 ± 289.9 days, local recurrence was not observed, but distant metastasis was observed in a single patient. Adverse events of grade 3 to grade 4 were not observed. The mean dose rate for Monaco was significantly lower than that for ERGO++ and SmartArc (P < 0.0001), and the beam-on time for Monaco was significantly longer than that for ERGO++ and SmartArc (P < 0.0001). Each TPS was successfully used for prostate VMAT planning without significant differences in early clinical outcomes despite significant TPS-specific delivery parameter variations. PMID:23401667

  7. Delivery Parameter Variations and Early Clinical Outcomes of Volumetric Modulated Arc Therapy for 31 Prostate Cancer Patients: An Intercomparison of Three Treatment Planning Systems

    PubMed Central

    Tsutsumi, Shinichi; Hosono, Masako N.; Tatsumi, Daisaku; Miki, Yoshitaka; Masuoka, Yutaka; Ogino, Ryo; Ishii, Kentaro; Shimatani, Yasuhiko; Miki, Yukio

    2013-01-01

    We created volumetric modulated arc therapy (VMAT) plans for 31 prostate cancer patients using one of three treatment planning systems (TPSs)—ERGO++, Monaco, or Pinnacle—and then treated those patients. A dose of 74 Gy was prescribed to the planning target volume (PTV). The rectum, bladder, and femur were chosen as organs at risk (OARs) with specified dose-volume constraints. Dose volume histograms (DVHs), the mean dose rate, the beam-on time, and early treatment outcomes were evaluated and compared. The DVHs calculated for the three TPSs were comparable. The mean dose rates and beam-on times for Ergo++, Monaco, and SmartArc were, respectively, 174.3 ± 17.7, 149.7 ± 8.4, and 185.8 ± 15.6 MU/min and 132.7 ± 8.4, 217.6 ± 13.1, and 127.5 ± 27.1 sec. During a follow-up period of 486.2 ± 289.9 days, local recurrence was not observed, but distant metastasis was observed in a single patient. Adverse events of grade 3 to grade 4 were not observed. The mean dose rate for Monaco was significantly lower than that for ERGO++ and SmartArc (P < 0.0001), and the beam-on time for Monaco was significantly longer than that for ERGO++ and SmartArc (P < 0.0001). Each TPS was successfully used for p